| 1. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 2. |
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| 3. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 4. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 5. |
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| 6. |
- Githumbi, Esther, et al.
(författare)
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Pollen-Based Maps of Past Regional Vegetation Cover in Europe Over 12 Millennia-Evaluation and Potential
- 2022
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media S.A.. - 2296-701X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Realistic and accurate reconstructions of past vegetation cover are necessary to study past environmental changes. This is important since the effects of human land-use changes (e.g. agriculture, deforestation and afforestation/reforestation) on biodiversity and climate are still under debate. Over the last decade, development, validation, and application of pollen-vegetation relationship models have made it possible to estimate plant abundance from fossil pollen data at both local and regional scales. In particular, the REVEALS model has been applied to produce datasets of past regional plant cover at 1 degrees spatial resolution at large subcontinental scales (North America, Europe, and China). However, such reconstructions are spatially discontinuous due to the discrete and irregular geographical distribution of sites (lakes and peat bogs) from which fossil pollen records have been produced. Therefore, spatial statistical models have been developed to create continuous maps of past plant cover using the REVEALS-based land cover estimates. In this paper, we present the first continuous time series of spatially complete maps of past plant cover across Europe during the Holocene (25 time windows covering the period from 11.7 k BP to present). We use a spatial-statistical model for compositional data to interpolate REVEALS-based estimates of three major land-cover types (LCTs), i.e., evergreen trees, summer-green trees and open land (grasses, herbs and low shrubs); producing spatially complete maps of the past coverage of these three LCTs. The spatial model uses four auxiliary data sets-latitude, longitude, elevation, and independent scenarios of past anthropogenic land-cover change based on per-capita land-use estimates ("standard" KK10 scenarios)-to improve model performance for areas with complex topography or few observations. We evaluate the resulting reconstructions for selected time windows using present day maps from the European Forest Institute, cross validate, and compare the results with earlier pollen-based spatially-continuous estimates for five selected time windows, i.e., 100 BP-present, 350-100 BP, 700-350 BP, 3.2-2.7 k BP, and 6.2-5.7 k BP. The evaluations suggest that the statistical model provides robust spatial reconstructions. From the maps we observe the broad change in the land-cover of Europe from dominance of naturally open land and persisting remnants of continental ice in the Early Holocene to a high fraction of forest cover in the Mid Holocene, and anthropogenic deforestation in the Late Holocene. The temporal and spatial continuity is relevant for land-use, land-cover, and climate research.
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| 7. |
- Hellamand, Pasoon, et al.
(författare)
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Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network
- 2024
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Ingår i: ARTHRITIS & RHEUMATOLOGY. - 2326-5191 .- 2326-5205.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. Results: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). Conclusion: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.
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| 8. |
- Klein, Alison P., et al.
(författare)
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An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer.PATIENTS AND METHODS: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates.RESULTS: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk.CONCLUSION: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.
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| 9. |
- Lindström, Annika K, et al.
(författare)
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Discrepancies in expression and prognostic value of tumor markers in adenocarcinoma and squamous cell carcinoma in cervical cancer
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:7, s. 2577-2578
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Tidskriftsartikel (refereegranskat)abstract
- The expression of 11 tumor markers in 129 women with squamous cell compared to 31 women with adenomatous cervical cancer was investigated to detect differences in expression. There was a significantly higher expression of p53, CD4, epidermal growth factor receptor (EGFR), CD44 and stratifin in squamous cell, compared to adenocarcinoma, while there was a higher expression of c-myc in adenocarcinoma. P-53, cyclooxygenase-2 (Cox-2) and c-myc significantly correlated to prognosis in squamous cell carcinoma, but none of the 11 investigated tumor markers had any prognostic value in adenocarcinomas. The prognostic value of individual tumor markers differs with the histological subtype in cervical cancer.
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| 10. |
- Lindström, Linda, 1978-, et al.
(författare)
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Chronic hypertension in women after perinatal exposure to preeclampsia, being born small for gestational age or preterm
- 2017
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 31:2, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is an established association between adverse events during perinatal life and chronic hypertension in adult life. However, disadvantageous conditions often coexist in the same pregnancy. We investigated single and joint perinatal exposure to preeclampsia, being born small for gestational age (SGA) or preterm and subsequent risk of chronic hypertension. Methods: The study population consisted of 731,008 primiparous women from Norway and Sweden registered in the Medical Birth Registers, both as infants and as first time mothers between 1967-2009 (Norway) and 1973-2010 (Sweden). Risk of chronic hypertension in early pregnancy was calculated in women perinatally exposed to preeclampsia, born SGA or preterm by log-binominal regression analysis, and adjusted for maternal age and level of education in the 1st generation. Results: The rate of chronic hypertension was 0.4%. Risk of chronic hypertension was associated with single perinatal exposure to preeclampsia, being born SGA or preterm with adjusted relative risks (95% confidence intervals, CI) 2.2 (95% CI 1.8, 2.7), 1.1 (95% CI 1.0, 1.3) and 1.3 (95% CI 1.0, 1.5) respectively. The risks increased after joint exposures, with an almost 4-fold risk increase after perinatal exposure to preeclampsia and preterm birth. Additional adjustment for BMI and smoking in the 2nd generation in a subset of the cohort only had a minor impact on the results. Conclusions: Perinatal exposure to preeclampsia, being born SGA or preterm is independently associated with increased risk of chronic hypertension. The highest risk was seen after exposure to preeclampsia, especially if combined with SGA or preterm birth.
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