| 1. |
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| 2. |
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 6. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 7. |
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| 8. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Forskningsöversikt (refereegranskat)
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| 9. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 11. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 12. |
- Huyghe, Jeroen R, et al.
(författare)
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Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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| 13. |
- Reinke, Beth A, et al.
(författare)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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| 14. |
- Su, Yu-Ru, et al.
(författare)
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Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 353-362
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91-1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.IMPACT: The proposed model has potential utility in risk-stratified colorectal cancer prevention.
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| 15. |
- Wang, Xiaofeng, et al.
(författare)
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Evidence for type ia supernova diversity from ultraviolet observations with the hubble space telescope
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 749:2, s. 126-
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Tidskriftsartikel (refereegranskat)abstract
- We present ultraviolet (UV) spectroscopy and photometry of four Type Ia supernovae (SNe 2004dt, 2004ef, 2005M, and 2005cf) obtained with the UV prism of the Advanced Camera for Surveys on the Hubble Space Telescope. This data set provides unique spectral time series down to 2000 angstrom. Significant diversity is seen in the near-maximum-light spectra (similar to 2000-3500 angstrom) for this small sample. The corresponding photometric data, together with archival data from Swift Ultraviolet/Optical Telescope observations, provide further evidence of increased dispersion in the UV emission with respect to the optical. The peak luminositiesmeasured in the uvw1/F250W filter are found to correlate with the B-band light-curve shape parameter Delta m(15)(B), but with much larger scatter relative to the correlation in the broadband B band (e.g., similar to 0.4 mag versus similar to 0.2 mag for those with 0.8 mag < Delta m(15)(B) < 1.7 mag). SN 2004dt is found as an outlier of this correlation (at > 3 sigma), being brighter than normal SNe Ia such as SN 2005cf by similar to 0.9 mag and similar to 2.0 mag in the uvw1/F250W and uvm2/F220W filters, respectively. We show that different progenitor metallicity or line-expansion velocities alone cannot explain such a large discrepancy. Viewing-angle effects, such as due to an asymmetric explosion, may have a significant influence on the flux emitted in the UV region. Detailed modeling is needed to disentangle and quantify the above effects.
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| 16. |
- Nounu, Aayah, et al.
(författare)
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A combined proteomics and mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : Elsevier. - 1055-9965 .- 1538-7755. ; 30:3, s. 564-575
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence for aspirin’s chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N ¼ 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N ¼ 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03–1.13; OR: 3.33, 95% CI, 2.46–4.50; and OR: 1.15, 95% CI, 1.02–1.29, respectively).Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin’s reduction of metastasis.Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
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| 17. |
- Nounu, Aayah, et al.
(författare)
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Salicylic Acid and Risk of Colorectal Cancer : A Two-Sample Mendelian Randomization Study
- 2021
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.
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| 18. |
- Thrift, Aaron P., et al.
(författare)
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Mendelian randomization study of height and risk of colorectal cancer
- 2015
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 662-672
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Tidskriftsartikel (refereegranskat)abstract
- Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.
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| 19. |
- O’Reilly, Catherine M., et al.
(författare)
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Rapid and highly variable warming of lake surface waters around the globe
- 2015
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:24
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Tidskriftsartikel (refereegranskat)abstract
- In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
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| 20. |
- Seyed Khoei, Nazlisadat, et al.
(författare)
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Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
- 2020
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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| 21. |
- Sharma, Sapna, et al.
(författare)
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A global database of lake surface temperatures collected by in situ and satellite methods from 1985–2009
- 2015
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Ingår i: Scientific Data. - : Macmillan Publishers Limited. - 2052-4463. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Global environmental change has influenced lake surface temperatures, a key driver of ecosystem structure and function. Recent studies have suggested significant warming of water temperatures in individual lakes across many different regions around the world. However, the spatial and temporal coherence associated with the magnitude of these trends remains unclear. Thus, a global data set of water temperature is required to understand and synthesize global, long-term trends in surface water temperatures of inland bodies of water. We assembled a database of summer lake surface temperatures for 291 lakes collected in situ and/or by satellites for the period 1985–2009. In addition, corresponding climatic drivers (air temperatures, solar radiation, and cloud cover) and geomorphometric characteristics (latitude, longitude, elevation, lake surface area, maximum depth, mean depth, and volume) that influence lake surface temperatures were compiled for each lake. This unique dataset offers an invaluable baseline perspective on global-scale lake thermal conditions as environmental change continues.
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| 22. |
- Branstrom, Richard, et al.
(författare)
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Perceptions of genetic research and testing among members of families with an increased risk of malignant melanoma
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:16, s. 3052-3062
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several melanoma susceptibility genes have been identified. As part of the international genetic research programme of the GenoMEL consortiums research on genetic mutations in melanoma families, the aim of this study was to examine family members' views about their risk of melanoma, gene testing and genetic research. Methods: Self-report data were gathered using online and paper-based surveys available in four languages among 312 individuals (62% from Europe, 18% from Australia, 13% from the United States of America (USA) and 7% from Israel). Results: Fifty three percent had been diagnosed with a melanoma, and 12% had a positive susceptibility gene test result. Respondents with many moles and freckles were more likely to perceive themselves at risk for developing melanoma (odds ratio [OR](Freckles) = 2.24 with 95% confidence interval [CI] = 1.18-4.26; ORMany (moles) = 6.92, 95% CI = 2.37-20.23). Respondents who had received a non-informative (negative) genetic test result were much less likely to perceive themselves at increased risk (OR = 0.17, 95% CI = 0.04-0.73). Safe-guards were perceived as important to protect genetic information, but there was also support for the storage and exchange of such information. Overall, respondents were in favour of genetic testing, even if current knowledge about melanoma risk genes is still limited. Contrary to previous studies, participants reported that a non-informative (negative) genetic test result, although not necessarily indicative of lower risk of melanoma, would be likely to reduce their practise of preventive behaviours. Conclusions: Participants were influenced by their phenotype and test results in risk estimations. They expressed positive views on genetic research and towards genetic testing, but reported that a non-informative (negative) test result might be associated with an (erroneous) perception of reduced risk and fewer preventive behaviours. These results highlight the urgency of improving the quality of genetic counselling and increasing the effectiveness of communication regarding genetic test results. (C) 2012 Elsevier Ltd. All rights reserved.
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| 23. |
- Mayes, Maureen D, et al.
(författare)
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Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
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Tidskriftsartikel (refereegranskat)abstract
- In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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| 24. |
- Baron, John A., et al.
(författare)
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Cigarette smoking, alcohol consumption, and risk of hip fracture in women
- 2001
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Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 161:7, s. 983-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies regarding the impact of cigarette smoking on the risk of hip fracture in postmenopausal women have been inconsistent, suggesting different effects in different groups. The effect of alcohol intake on fracture risk is puzzling: moderate alcohol intake appears to increase bone density, and its association with hip fracture is not clear. METHODS: To assess the associations of cigarette smoking and alcohol consumption with hip fracture risk among postmenopausal women, we conducted an analysis of a population-based case-control study from Sweden. Cases were postmenopausal women, aged 50 to 81 years, who sustained a hip fracture after minor trauma between October 1, 1993, and February 28, 1995; controls were randomly selected from a population-based register during the same period. A mailed questionnaire requesting information on lifestyle habits and medical history was used 3 months after the hip fracture for cases and simultaneously for controls. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed by means of logistic regression. RESULTS: Of those eligible, 1328 cases (82.5%) and 3312 controls (81.6%) responded. Compared with never smokers, current smokers had an increased risk of hip fracture (age-adjusted OR, 1.66; 95% CI, 1.41-1.95). Duration of smoking-particularly postmenopausal smoking-was more important than the amount smoked. Former smokers had a small increase in risk (age-adjusted OR, 1.15; 95% CI, 0.97-1.37) that decreased with the duration of cessation. The age-adjusted OR for women consuming alcohol was 0.80 (95% CI, 0.69-0.93). CONCLUSIONS: Cigarette smoking is a risk factor for hip fracture among postmenopausal women; risk decreases after cessation. Alcohol consumption has a weak inverse association with risk.
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| 25. |
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| 26. |
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| 27. |
- Chioncel, Ovidiu, et al.
(författare)
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Epidemiology, pathophysiology and contemporary management of cardiogenic shock - a position statement from the Heart Failure Association of the European Society of Cardiology
- 2020
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:8, s. 1315-1341
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Tidskriftsartikel (refereegranskat)abstract
- Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patients underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management.
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| 28. |
- Farahmand, Bahman Y., et al.
(författare)
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Body Size and Hip Fracture Risk : Swedish Hip Fracture Study Group
- 2000
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Ingår i: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983 .- 1531-5487. ; 11:2, s. 214-9
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this population-based case-control study was to determine the independent association between height, weight at different ages and adult weight change on hip fracture risk, and the joint effects of these factors. The study base comprised postmenopausal women 50-81 years of age who resided in six counties in Sweden during the period October 1993 to February 1995. The study included 1,327 cases with an incident hip fracture and 3,262 randomly selected controls. We obtained information on body measures and other factors possibly related to hip fracture through mailed questionnaires and telephone interviews. Height and weight change were dominant risk factors. Tall women (> or = 169 cm) had an odds ratio of 3.16 (95% confidence interval = 2.47-4.05) compared with women shorter than 159 cm. Weight gain during adult life was strongly protective: compared with those with moderate weight change (-3 to 3 kg), those with substantial weight gain (> or =12 kg) had a markedly decreased risk of hip fracture (odds ratio = 0.35; 95% confidence interval = 0.27-0.45), whereas weight loss was associated with an increased risk. Weight change retained important effects among all subjects, even after controlling for current weight and weight at age 18. In contrast, among women who gained weight, the separate effects of current weight and weight at age 18 were small or absent. Among women who lost weight, both current weight and weight at age 18 had effects that remained after controlling for weight change. Adult weight change and height are dominant body size risk factors for hip fracture. Weight loss vs weight changes demarcates different patterns of hip fracture risk.
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| 29. |
- Farahmand, Bahman Y., et al.
(författare)
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Physical activity and hip fracture : a population-based case-control study
- 2000
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Ingår i: International Journal of Epidemiology. - 0300-5771 .- 1464-3685. ; 29:2, s. 308-14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A growing body of literature suggests that physical activity may be a protective factor against hip fracture. METHODS: To study the association between hip fracture risk and recreational physical activity at various ages, changes in activity during adult life, occupational physical activity and how risks vary by adult weight change, we performed a population-based case-control study among postmenopausal women aged 50-81 years residing in six counties in Sweden in 1993-1995. The analysis consisted of 1327 women with hip fracture and 3262 randomly selected controls. Information on leisure physical activity before age 18, at 18-30 years and during recent years was based on a questionnaire. Data on occupational physical activity were collected through an independent classification of job titles obtained from record linkage with census data from 1960, 1970 and 1980. RESULTS: There was a protective effect of recent leisure physical activity. Compared to women who reported no leisure activity, the odds ratios (OR) were 0.79 (95% CI: 0.62-1.00), 0.67 (95% CI: 0.54-0.84) and 0.48 (95% CI: 0.39-0.60) for women who exercised <1 h per week, 1-2 h per week, and 3+ h per week, respectively. These decreased OR were more pronounced in women who had lost weight after 18 years of age than in those who had gained weight. Women with high physical activity at both 18-30 years and during recent years did not have a stronger protection than those with isolated high activity late in life, after accounting for recent activity. Occupational physical activity was not associated with hip fracture risk in this study. CONCLUSIONS: Recent physical activity is protective against hip fracture. The protective effect is most pronounced in women who had lost weight after age 18.
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| 30. |
- Farahmand, Bahman Y., et al.
(författare)
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Socioeconomic status, marital status and hip fracture risk : a population-based case-control study
- 2000
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 11:9, s. 803-8
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Tidskriftsartikel (refereegranskat)abstract
- Socioeconomic status and social support have been identified as important determinants of several diseases and overall mortality, but these factors have not been adequately examined in relation to hip fracture risk. The aim of this study was to determine the relationship of socioeconomic status and marital status to hip fracture risk. We used data from a population-based case-control study in postmenopausal women aged 50-81 years during 1993-1995 who resided in six counties in Sweden. The analysis was based on 1327 incident cases of hip fracture and 3262 randomly selected controls. Socioeconomic and marital status were obtained by record linkage with census data in 1960, 1970, 1980 and 1990. Information on other possible risk factors for hip fracture was collected by a mailed questionnaire. Women who were gainfully employed in 1990 had an odds ratio (OR) of 0.74 [95% confidence interval (CI) 0.56-0.96] compared with those not gainfully employed; those in the highest tertile of household income had an OR of 0.74 (95% CI 0.60-0.90) compared with those in the lowest tertile of income. Women who lived in a one-family house had an OR of 0.85 (95% CI 0.72-0.99) compared with those living in an apartment. Divorced, widowed or unmarried women had a higher risk of hip fracture than married or cohabiting women; the OR was 1.40 (95% CI 1.06-1.85). Married women who were both gainfully employed and were living in a one-family house had a substantially decreased risk of hip fracture compared with unemployed women living without a partner in an apartment (OR 0.39; 95% CI 0.22-0.71). Occupational affiliation among women ever employed, and educational level, were not associated with hip fracture risk. We conclude that employment, household income, type of housing and marital status seem to be risk indicators of hip fracture risk independent of known osteoporotic risk factors.
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| 31. |
- Farahmand, Bahman Y., et al.
(författare)
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Survival after hip fracture
- 2005
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:12, s. 1583-90
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Tidskriftsartikel (refereegranskat)abstract
- Although it is known that overall mortality is increased after hip fracture, the influence of hip fracture risk factors on the subsequent mortality and cause of death has not been well studied. The objective of this study was to establish the survival after hip fracture in women and to assess the impact of comorbidity on mortality. We identified a complete population-based set of 2,245 incident hip fracture cases and 4,035 randomly selected population-based controls among women 50-81 years old in Sweden and followed these subjects for an average of 5 years through the Swedish National Inpatient and Cause-of-Death Registers. Information on factors related to hip fracture was obtained through linkage to hospital discharge data and through a mailed questionnaire. We studied excess mortality of hip fracture patients compared to controls using survival curves and proportional hazard regression models. During follow-up, 896 hip fracture patients (40%) and 516 (13%) controls died. The relative risk (RR) of death, adjusted for age and previous hospitalization for serious disease, was 2.3 (95% CI 2.0-2.5). Although the highest mortality risks were in the 1st 6 months post-fracture, RRs for fractures versus controls were increased for at least 6 years. Increased mortality was apparent both in those with evidence of comorbidity and those without. Hip fracture patients have a substantially increased risk of death that persists for at least 6 years post-fracture. The relative excess mortality is independent of comorbidity and known hip fracture risk factors.
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| 32. |
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| 33. |
- Holmberg, Lars, et al.
(författare)
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Alcohol intake and breast cancer risk : effect of exposure from 15 years of age
- 1995
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 4:8, s. 843-847
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Tidskriftsartikel (refereegranskat)abstract
- Research regarding the relationship between alcohol intake and breast cancer risk has suggested an association between the two, although the data are inconsistent regarding dose effects and susceptible populations. To clarify these issues, we investigated the association of breast cancer risk with alcohol intake at various ages in a population-based case-control study nested within a screening cohort in Sweden. Subjects were women 40-75 years old who participated in a screening program in central Sweden. Information about personal characteristics, diet, and alcohol intake was obtained by a questionnaire sent out at the invitation to the screening interview and at a supplementary interview conducted among a sample of women who did and did not develop breast cancer. Alcohol intake did not affect breast cancer risk among women under 50 years old. However, among those over 50 years of age, ever-drinking conferred a relative risk of 1.8 (95% confidence interval = 1.2-2.6). Current and former drinkers had similar increases in risk. No particular latent period of alcohol effect was identified, but drinking later in life to have a bigger effect than did drinking earlier in life.
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| 34. |
- Kasimova, Marina A., et al.
(författare)
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Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization- dependent gating
- 2019
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Ingår i: eLIFE. - : NLM (Medline). - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to most voltage-gated ion channels, hyperpolarization- and cAMP gated (HCN) ion channels open on hyperpolarization. Structure-function studies show that the voltagesensor of HCN channels are unique but the mechanisms that determine gating polarity remain poorly understood. All-atom molecular dynamics simulations (similar to 20 mu s) of HCN1 channel under hyperpolarization reveals an initial downward movement of the S4 voltage-sensor but following the transfer of last gating charge, the S4 breaks into two sub-helices with the lower sub-helix becoming parallel to the membrane. Functional studies on bipolar channels show that the gating polarity strongly correlates with helical turn propensity of the substituents at the breakpoint. Remarkably, in a proto-HCN background, the replacement of breakpoint serine with a bulky hydrophobic amino acid is sufficient to completely flip the gating polarity from inward to outward-rectifying. Our studies reveal an unexpected mechanism of inward rectification involving a linker sub-helix emerging from HCN S4 during hyperpolarization.
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| 35. |
- Larsson, Susanna C., et al.
(författare)
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Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants : A mendelian randomization study
- 2021
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 40:5, s. 3332-3337
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to pro-inflammatory eicosanoids, which according to experimental research modulate tumor cell proliferation, differentiation, and apoptosis. We employed the Mendelian randomization design to test the hypothesis that higher plasma phospholipid AA concentrations are associated with increased risk of 10 site-specific cancers.METHODS: Two genetic variants associated with plasma phospholipid concentrations of AA (rs174547 in FADS1 [P = 3.0 × 10-971] and rs16966952 in PDXDC1 [P = 2.4 × 10-10]) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium were used as genetic instruments. The associations of those variants with cancer were taken from the UK Biobank (n = 367,643), FinnGen consortium (n = 135,638), International Lung Cancer Consortium (n = 27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254), Breast Cancer Association Consortium (n = 228,951), Ovarian Cancer Association Consortium (n = 66,450), and BioBank Japan (n = 212,453).RESULTS: Higher genetically predicted plasma phospholipid AA concentrations were associated with increased risk of colorectal and lung cancer. Results were consistent across data sources and variants. The combined odds ratios per standard deviation increase of AA concentrations were 1.08 (95% CI 1.05-1.11; P = 6.3 × 10-8) for colorectal cancer and 1.07 (95%CI 1.05-1.10; P = 3.5 × 10-7) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02-1.17; P = 0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary.CONCLUSION: These results indicate that AA may be implicated in the development of colorectal and lung cancer and possibly esophageal cancer. Treatments with plasma AA-lowering properties should be evaluated for clinical benefit.
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| 36. |
- Larsson, Susanna C., et al.
(författare)
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Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer : a two-sample Mendelian randomization study
- 2020
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Observational studies have shown that milk consumption is inversely associated with colorectal, bladder, and breast cancer risk, but positively associated with prostate cancer. However, whether the associations reflect causality remains debatable. We investigated the potential causal associations of milk consumption with the risk of colorectal, bladder, breast, and prostate cancer using a genetic variant near the LCT gene as proxy for milk consumption.METHODS: We obtained genetic association estimates for cancer from the UK Biobank (n = 367,643 women and men), FinnGen consortium (n = 135,638 women and men), Breast Cancer Association Consortium (n = 228,951 women), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254 men). Milk consumption was proxied by a genetic variant (rs4988235 or rs182549) upstream of the gene encoding lactase, which catalyzes the breakdown of lactose.RESULTS: Genetically proxied milk consumption was associated with a reduced risk of colorectal cancer. The odds ratio (OR) for each additional milk intake increasing allele was 0.95 (95% confidence interval [CI] 0.91-0.99; P = 0.009). There was no overall association of genetically predicted milk consumption with bladder (OR 0.99; 95% CI 0.94-1.05; P = 0.836), breast (OR 1.01; 95% CI 1.00-1.02; P = 0.113), and prostate cancer (OR 1.01; 95% CI 0.99-1.02; P = 0.389), but a positive association with prostate cancer was observed in the FinnGen consortium (OR 1.07; 95% CI 1.01-1.13; P = 0.026).CONCLUSIONS: Our findings strengthen the evidence for a protective role of milk consumption on colorectal cancer risk. There was no or limited evidence that milk consumption affects the risk of bladder, breast, and prostate cancer.
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| 37. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Combined associations of body mass index and adherence to a Mediterranean-like diet with all-cause and cardiovascular mortality : A cohort study
- 2020
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality.Methods and findingsOur longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997–2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6–8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson’s weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96–1.11). In contrast, compared with those with normal weight and high mMED, individuals with a low mMED had a high mortality despite a normal BMI (HR 1.60; 95% CI 1.48–1.74). We found similar estimates among women and men. For CVD mortality (12,064 deaths) the findings were broadly similar, though obese individuals with high mMED retained a modestly increased risk of CVD death (HR 1.29; 95% CI 1.16–1.44) compared with those with normal weight and high mMED. A main limitation of the present study is the observational design with self-reported lifestyle information with risk of residual or unmeasured confounding (e.g., genetic liability), and no causal inferences can be made based on this study alone.ConclusionsThese findings suggest that diet quality modifies the association between BMI and all-cause mortality in women and men. A healthy diet may, however, not completely counter higher CVD mortality related to obesity.
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| 38. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Differences in Risk Factor Patterns Between Cervical and Trochanteric Hip Fractures
- 1999
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 10:6, s. 487-494
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Tidskriftsartikel (refereegranskat)abstract
- The two types of hip fracture--cervical and trochanteric femoral fractures--are generally considered together in etiologic studies. However, women with a trochanteric fracture may be more osteoporotic than those with cervical hip fractures, and have higher post-fracture mortality. To explore differences in risk factor patterns between the two types of hip fracture we used data from a large population-based case-control study in Swedish women, 50-81 years of age. Data were collected by questionnaire, to which more than 80% of subjects responded. Of the cases included, 811 had had a cervical fracture and 483 a trochanteric fracture during the study period; these cases were compared with 3312 randomly selected controls. Height and hormonal factors appeared to affect the risk of the two types of hip fracture differently. For every 5 cm of current height, women with a cervical fracture had an adjusted odds ratio (OR) of 1.23 (95% CI 1.15-1.32) compared with an OR of 1.06 (95% CI 0.97-1.15) for women with trochanteric fractures. Later menopausal age was protective for trochanteric fractures (OR 0.95, 95% CI 0. 91-0.99 per 2 years) but no such association was found for cervical fractures. Compared with never smokers, current smokers had an OR of 1.48 (95% CI 1.12-1.95) for trochanteric fractures and 1.22 (95% CI 0.98-1.52) for cervical fractures. Current hormone replacement therapy was similarly protective for both fracture types, but former use substantially reduced risk only for trochanteric fractures: OR 0. 55 (95% CI 0.33-0.92) compared with 1.00 (95% CI 0.71-1.39) for cervical fractures. These risk factor patterns suggest etiologic differences between the fracture types which have to be considered when planning preventive interventions.
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| 39. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Hormone replacement therapy and hip fracture risk : population based case-control study
- 1998
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Ingår i: BMJ - British Medical Journal. - 1756-1833. ; 316:7148, s. 1858-63
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. Setting: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.
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| 40. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Influence of parity and lactation on hip fracture risk
- 2001
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 153:12, s. 1166-1172
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Tidskriftsartikel (refereegranskat)abstract
- Several studies indicate that parity and lactation are associated with modest, short-term bone loss, but the long-term effect on osteoporotic fracture risk is uncertain. The authors therefore analyzed data from a population-based case-control study among Swedish postmenopausal women aged 50-81 years between October 1993 and February 1995. Mailed questionnaires and telephone interviews were used to collect data on 1,328 incident cases with hip fracture and 3,312 randomly selected controls. In age-adjusted analyses, the risk of hip fracture among all women was reduced by 10% per child (95% confidence interval (CI): 5, 14). After multivariate adjustment including body mass index as a covariate, the risk reduction was 5% per child (95% CI: 0, 10). Oral contraceptive use modified the association of parity with hip fracture risk. Among never users of oral contraceptives, the risk of hip fracture was reduced by 8% per child (95% CI: 2, 13), whereas among ever users of oral contraceptives, the risk was in the opposite direction, with an increase in risk by 19% per child (95% CI: 0, 41). After parity was considered, there was no association of duration of lactation period with fracture risk. The authors conclude that parity is modestly associated with a reduced hip fracture risk among women who had not used oral contraceptives previously.
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| 41. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Oral contraceptive use and hip fracture risk : a case-control study
- 1999
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 353:9175, s. 1481-1484
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. METHOD: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded. FINDINGS: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30. INTERPRETATION: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.
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| 42. |
- Michaëlsson, Karl, et al.
(författare)
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Serum 25-hydroxyvitamin D is associated with fracture risk only during periods of seasonally high levels in women with a high body mass index
- 2021
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:10, s. 1957-1966
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Tidskriftsartikel (refereegranskat)abstract
- Serum 25-hydroxyvitamin D (S-25OHD) is used to assess vitamin D status and is known to be affected by season and fat mass. Because these factors are often ignored when interpreting S-25OHD, assessment of vitamin D associations with disease outcomes may be distorted. We aimed to investigate the impact of season of blood draw and fat mass on the association of S25OHD with fracture risk. We enrolled 5000 women, mean ± SD age 68 ± 7 years, with dual-energy x-ray absorptiometry (DXA) scans and blood collection in a population-based cohort. Proportional hazards regression, stratified by season and fat mass, was used to determine hazard ratios (HRs) of fracture according to categories of S-25OHD. Our secondary exposures were serum 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3 ), the most active vitamin D metabolite and plasma parathyroid hormone (P-PTH). During an average of 9.2 years of follow-up, 1080 women had a fracture. Women with S-25OHD <30 nmol/L drawn during sunny months (May-October) had a multivariable-adjusted fracture HR of 2.06 (95% CI, 1.27-3.35) compared with those with S-25OHD >60 nmol/L; those with S-25OHD 30-40 nmol/L had an HR of 1.59 (95% CI, 1.12-2.26). In contrast, S-25OHD drawn during November through April was unrelated to fracture risk. The increased risk with low sunny season S-25OHD was seen only among women with body mass index (BMI) ≥25 kg/m2 or fat mass index (FMI) ≥9.8 kg/m2 . High fat mass and low S-25OHD were independently related to lower S-1,25-dihydroxycholecalciferol, which itself predicted fracture risk with samples collected during the sunny season. Irrespective of season, P-PTH was unrelated to fracture risk. We conclude that S-25OHD is associated with fracture risk only if drawn during periods of seasonally high levels in women with a high BMI. These results have implications for the evaluation of vitamin D status and can explain the lack of effect seen with vitamin D supplementation in many fracture trials. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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| 43. |
- Michaëlsson, Madeleine, 1968-, et al.
(författare)
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The impact and causal directions for the associations between diagnosis of ADHD, socioeconomic status, and intelligence by use of a bi-directional two-sample Mendelian randomization design
- 2022
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Previous studies have reported associations between attention-deficit/hyperactivity disorder (ADHD) and lower socioeconomic status and intelligence. We aimed to evaluate the causal directions and strengths for these associations by use of a bi-directional two-sample Mendelian randomization (MR) design. Methods We used summary-level data from the largest available genome-wide association studies (GWAS) to identify genetic instruments for ADHD, intelligence, and markers of socioeconomic status including the Townsend deprivation index, household income, and educational attainment. Effect estimates from individual genetic variants were combined using inverse-variance weighted regression. Results A genetically predicted one standard deviation (SD) increment in the Townsend deprivation index conferred an odds ratio (OR) of 5.29 (95% confidence interval (CI) 1.89-14.76) for an ADHD diagnosis (p<0.001). A genetically predicted one SD higher education level conferred an OR of 0.30 (95% CI 0.25-0.37) (p<0.001), and a genetically predicted one SD higher family income provided an OR of 0.35 (95% CI 0.25-0.49; p<0.001). The associations remained after adjustment for intelligence whereas the lower odds of an ADHD diagnosis with higher intelligence did not persist after adjustment for liability to greater educational attainment (adjusted OR 1.03, 95% CI 0.68-1.56; p=0.87). The MR analysis of the effect of ADHD on socioeconomic markers found that genetic liability to ADHD was statistically associated with each of them (p<0.001) but not intelligence. However, the average change in the socioeconomic markers per doubling of the prevalence of ADHD corresponded only to 0.05-0.06 SD changes. Conclusions Our results indicate that an ADHD diagnosis may be a direct and strong intelligence-independent consequence of socioeconomic related factors, whereas ADHD appears to lead only to modestly lowered socioeconomic status. Low intelligence seems not to be a major independent cause or consequence of ADHD.
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| 44. |
- Roettenbacher, Rachael M., et al.
(författare)
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Contemporaneous Imaging Comparisons of the Spotted Giant sigma Geminorum Using Interferometric, Spectroscopic, and Photometric Data
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 849:2
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Tidskriftsartikel (refereegranskat)abstract
- Nearby active stars with relatively rapid rotation and large starspot structures offer the opportunity to compare interferometric, spectroscopic, and photometric imaging techniques. In this paper, we image a spotted star with three different methods for the first time. The giant primary star of the RS Canum Venaticorum binary sigma. Geminorum (sigma Gem) was imaged for two epochs of interferometric, high-resolution spectroscopic, and photometric observations. The light curves from the reconstructions show good agreement with the observed light curves, supported by the longitudinally consistent spot features on the different maps. However, there is strong disagreement in the spot latitudes across the methods.
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| 45. |
- Stattin, Karl, et al.
(författare)
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Fracture risk across a wide range of physical activity levels, from sedentary individuals to elite athletes.
- 2021
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 153
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine how physical activity is associated with risk of different fracture outcomes across the full range of physical activity.METHODS: By combining information from three cohort studies and using generalized structural equation modelling, we estimated a continuous unitless latent variable reflecting physical activity that ranged from sedentary through elite athlete levels. Associations between physical activity and fracture outcomes were assessed with proportional hazards regression using restricted cubic splines with the mean physical activity (corresponding to 20-40 min walking or bicycling/day or 2-3 h exercise/week) as reference.RESULTS: Among 63,980 men and women (49-68 years) and during 13 years of follow-up, 8506 fractures occurred, including 2164 distal forearm, 779 proximal humerus, 346 clinical spine, and 908 hip fractures. Both lower and higher physical activity was associated with higher risk of any fracture compared to the mean. Physical activity at 1 standard deviation (SD) below the mean, corresponding to walking/bicycling <20 min/day or exercising <1-1 h/week, was associated with a lower risk of distal forearm fracture (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.85-0.99) and higher risk of hip fracture (HR: 1.24, 95% CI: 1.13-1.37), but no associations were seen above the mean physical activity level for these fractures. Physical activity was not associated with proximal humerus fracture but had a possible U-shaped association with clinical spine fracture.CONCLUSION: Physical activity was non-linearly associated with fracture risk and the association differed across fracture sites. Up to 2-3 h weekly exercise is beneficial for the prevention of hip fracture but may increase the risk of distal forearm fracture.
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| 46. |
- Sörensen, Jens, et al.
(författare)
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Myocardial Efficiency : A Fundamental Physiological Concept on the Verge of Clinical Impact
- 2020
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Ingår i: JACC Cardiovascular Imaging. - : Elsevier BV. - 1936-878X .- 1876-7591. ; 13:7, s. 1564-1576
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial external efficiency is the relation of mechanical energy generated by the left (or right) ventricle to the consumed chemical energy from aerobic metabolism. Efficiency can be calculated invasively, and, more importantly, noninvasively by using positron emission tomography, providing a single parameter by which to judge the adequacy of myocardial metabolism to generated mechanical output. This parameter has been found to be impaired in heart failure of myocardial or valvular etiology, and it changes in a characteristic manner with medical or interventional cardiac therapy. The authors discuss the concept, strengths, and limitations, known applications, and future perspectives of the use of myocardial efficiency.
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| 47. |
- Terry, Paul, et al.
(författare)
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Dietary calcium and vitamin D intake and risk of colorectal cancer : a prospective cohort study in women
- 2002
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Ingår i: Nutrition and Cancer. - 0163-5581 .- 1532-7914. ; 43:1, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- Although laboratory data and a few adenoma prevention trials suggest that calcium supplementation may reduce the risk of colorectal neoplasia, the results of observational studies of calcium intake and colorectal cancer risk are contradictory. However, few studies have examined the association among women or effects in specific colon subsites. Women with colorectal cancer diagnosed through 31 December 2000 were identified by linkage to regional cancer registries. During an average 11.3 yr of follow-up of 61,463 women, we observed 572 incident cases of colorectal cancer. Using data obtained from a 67-item food frequency questionnaire and Cox proportional hazards models to estimate rate ratios and 95% confidence intervals, we found an inverse association between dietary calcium intake and colorectal cancer risk. Women with the highest calcium intake (median 914 mg/day) had a reduced risk of colorectal cancer (rate ratio = 0.72, 95% confidence interval = 0.056-0.93, P for trend = 0.02) compared with women with the lowest intake (median 486 mg/day). Furthermore, our results suggest that the inverse association may be strongest in relation to distal cancers and among older women. The association with dairy products was less clear, suggesting that calcium intake per se is more important than specific calcium sources. Vitamin D intake was not clearly associated with risk. In sum, our data suggest that high calcium intake may lower colorectal cancer risk.
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| 48. |
- Titova, Olga E, et al.
(författare)
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Anger frequency and risk of cardiovascular morbidity and mortality
- 2022
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Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:4, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Anger may increase the risk of cardiovascular diseases (CVDs) but previous findings are inconclusive and large prospective studies are needed. We investigated whether frequency of strong anger is associated with the incidence of specific CVDs and CVD mortality, and if sex, age, and cardiometabolic risk factors modify these associations.Methods and results: We used data from a population-based cohort of 47 077 Swedish adults (56-94 years of age) who completed questionnaires regarding their experience of anger, lifestyle habits, and health characteristics. Participants were followed for incident cardiovascular outcomes and death up to 9 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios and confidence intervals adjusted for potential confounders were assessed.In multivariable analyses, frequent episodes of strong anger were associated with an increased risk of heart failure, atrial fibrillation, and CVD mortality [hazard ratios (95% confidence intervals) = 1.19 (1.04-1.37), 1.16 (1.06-1.28), and 1.23 (1.09-1.40), respectively]. The link between anger frequency and heart failure was more pronounced in men and participants with a history of diabetes. No evidence of an independent association of anger frequency with risk of myocardial infarction, aortic valve stenosis, and abdominal aortic aneurysm was found.Conclusion: Our findings indicate that anger may contribute to the development of specific CVDs and CVD mortality, especially heart failure in men and in those with diabetes.
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| 49. |
- Titova, Olga E., et al.
(författare)
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Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass
- 2023
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Ingår i: International Journal of Obesity. - : Springer Nature. - 1476-5497 .- 0307-0565. ; 47:11, s. 1043-1049
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Tidskriftsartikel (refereegranskat)abstract
- Background: The underlying molecular pathways for the effect of excess fat mass on cardiometabolic diseases is not well understood. Since body mass index is a suboptimal measure of body fat content, we investigated the relationship of fat mass measured by dual-energy X-ray absorptiometry with circulating cardiometabolic proteins. Methods: We used data from a population-based cohort of 4950 Swedish women (55–85 years), divided into discovery and replication samples; 276 proteins were assessed with three Olink Proseek Multiplex panels. We used random forest to identify the most relevant biomarker candidates related to fat mass index (FMI), multivariable linear regression to further investigate the associations between FMI characteristics and circulating proteins adjusted for potential confounders, and principal component analysis (PCA) for the detection of common covariance patterns among the proteins. Results: Total FMI was associated with 66 proteins following adjustment for multiple testing in discovery and replication multivariable analyses. Five proteins not previously associated with body size were associated with either lower FMI (calsyntenin-2 (CLSTN2), kallikrein-10 (KLK10)), or higher FMI (scavenger receptor cysteine-rich domain-containing group B protein (SSC4D), trem-like transcript 2 protein (TLT-2), and interleukin-6 receptor subunit alpha (IL-6RA)). PCA provided an efficient summary of the main variation in FMI-related circulating proteins involved in glucose and lipid metabolism, appetite regulation, adipocyte differentiation, immune response and inflammation. Similar patterns were observed for regional fat mass measures. Conclusions: This is the first large study showing associations between fat mass and circulating cardiometabolic proteins. Proteins not previously linked to body size are implicated in modulation of postsynaptic signals, inflammation, and carcinogenesis.
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| 50. |
- Titova, Olga E, et al.
(författare)
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Self-reported symptoms of sleep-disordered breathing and risk of cardiovascular diseases : Observational and Mendelian randomization findings
- 2022
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Ingår i: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- Sleep-disordered breathing may increase the risk of cardiovascular diseases, but observational findings are inconclusive. We investigated whether sleep-disordered breathing-related symptoms are associated with risk of several cardiovascular diseases using data from a cohort study and by performing Mendelian randomization analyses. The cohort study included 43,624 adults (56-94 years old) who completed questionnaires regarding symptoms of snoring and cessation of breathing, lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular diseases and death over 8 years through linkage to the Swedish National Patient and Death Registers. The Mendelian randomization analyses were conducted using single-nucleotide polymorphisms robustly associated with sleep apnea in a recent genome-wide association study and summary-level data for major cardiovascular diseases from large-scale consortia. In the cohort study, an increased risk of atrial fibrillation was observed in participants who reported both snoring and cessation of breathing (hazard ratio [95% confidence interval] = 1.16 [1.03-1.30]) compared with those without sleep-disordered breathing symptoms. There was no association between sleep-disordered breathing symptoms and risk of myocardial infarction, heart failure, aortic valve stenosis or abdominal aortic aneurysm in multivariable analyses. Mendelian randomization analyses showed no association of genetic liability to sleep apnea with myocardial infarction, heart failure or atrial fibrillation, but revealed a suggestive association with coronary artery disease (odds ratio [95% confidence interval] = 1.24 [1.02-1.52]).
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