| 51. |
- Sung, Yun Ju, et al.
(författare)
-
A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
-
Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 52. |
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| 53. |
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| 54. |
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| 55. |
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| 56. |
- Bogers, M., et al.
(författare)
-
The open innovation research landscape : established perspectives and emerging themes across different levels of analysis
- 2017
-
Ingår i: Industry and Innovation. - : Routledge. - 1366-2716 .- 1469-8390. ; 24:1, s. 8-40
-
Tidskriftsartikel (refereegranskat)abstract
- This paper provides an overview of the main perspectives and themes emerging in research on open innovation (OI). The paper is the result of a collaborative process among several OI scholars–having a common basis in the recurrent Professional Development Workshop on ‘Researching Open Innovation’ at the Annual Meeting of the Academy of Management. In this paper, we present opportunities for future research on OI, organised at different levels of analysis. We discuss some of the contingencies at these different levels, and argue that future research needs to study OI–originally an organisational-level phenomenon–across multiple levels of analysis. While our integrative framework allows comparing, contrasting and integrating various perspectives at different levels of analysis, further theorising will be needed to advance OI research. On this basis, we propose some new research categories as well as questions for future research–particularly those that span across research domains that have so far developed in isolation.
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| 57. |
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| 58. |
- Czamara, D, et al.
(författare)
-
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
-
Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 59. |
- Döringer, Nora, et al.
(författare)
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Motivational Interviewing to Prevent Childhood Obesity: A Cluster RCT
- 2016
-
Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 137:5
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective was to evaluate a manualized theory-driven primary preventive intervention aimed at early childhood obesity. The intervention was embedded in Swedish child health services, starting when eligible children were 9 to 10 months of age and continuing until the children reached age 4. METHODS: Child health care centers in 8 Swedish counties were randomized into intervention and control units and included 1355 families with 1369 infants. Over similar to 39 months, families in the intervention group participated in 1 group session and 8 individual sessions with a nurse trained in motivational interviewing, focusing on healthy food habits and physical activity. Families in the control group received care as usual. Primary outcomes were children's BMI, overweight prevalence, and waist circumference at age 4. Secondary outcomes were children's and mothers' food and physical activity habits and mothers' anthropometrics. Effects were assessed in linear and log-binominal regression models using generalized estimating equations. RESULTS: There were no statistically significant differences in children's BMI (beta = -0.11, 95% confidence interval [CI]: -0.31 to 0.08), waist circumference (beta = -0.48, 95% CI: -0.99 to 0.04), and prevalence of overweight (relative risk = 0.95, 95% CI: 0.69 to 1.32). No significant intervention effects were observed in mothers' anthropometric data or regarding mothers' and children's physical activity habits. There was a small intervention effect in terms of healthier food habits among children and mothers. CONCLUSIONS: There were no significant group differences in children's and mothers' anthropometric data and physical activity habits. There was, however, some evidence suggesting healthier food habits, but this should be interpreted with caution.
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| 60. |
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| 61. |
- Jonsson, Lina, 1982, et al.
(författare)
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Rare and Common Variants Conferring Risk of Tooth Agenesis
- 2018
-
Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 97:5, s. 515-522
-
Tidskriftsartikel (refereegranskat)abstract
- We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.
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| 62. |
- LeBlanc, K, et al.
(författare)
-
Quality of Life after Hernia Surgery
- 2015
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Ingår i: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S127-31
-
Tidskriftsartikel (refereegranskat)
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| 63. |
- Madsen, I. E. H., et al.
(författare)
-
Job strain as a risk factor for clinical depression : systematic review and meta-analysis with additional individual participant data
- 2017
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 47:8, s. 1342-1356
-
Forskningsöversikt (refereegranskat)abstract
- Background. Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. Method. We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. Results. We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). Conclusions. Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
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| 64. |
- Shungin, Dmitry, et al.
(författare)
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Using genetics to test the causal relationship of total adiposity and periodontitis : Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium
- 2015
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 638-650
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI: 1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.
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| 65. |
- Styrkarsdottir, Unnur, et al.
(författare)
-
Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
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| 66. |
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| 67. |
- Yokoyama, Y, et al.
(författare)
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Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project
- 2016
-
Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 19:2, s. 112-124
-
Tidskriftsartikel (refereegranskat)abstract
- We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
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| 68. |
- Barrigón, E., et al.
(författare)
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GaAs Nanowire pn-Junctions Produced by Low-Cost and High-Throughput Aerotaxy
- 2018
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 18:2, s. 1088-1092
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Tidskriftsartikel (refereegranskat)abstract
- Semiconductor nanowires could significantly boost the functionality and performance of future electronics, light-emitting diodes, and solar cells. However, realizing this potential requires growth methods that enable high-throughput and low-cost production of nanowires with controlled doping. Aerotaxy is an aerosol-based method with extremely high growth rate that does not require a growth substrate, allowing mass-production of high-quality nanowires at a low cost. So far, pn-junctions, a crucial element of solar cells and light-emitting diodes, have not been realized by Aerotaxy growth. Here we report a further development of the Aerotaxy method and demonstrate the growth of GaAs nanowire pn-junctions. Our Aerotaxy system uses an aerosol generator for producing the catalytic seed particles, together with a growth reactor with multiple consecutive chambers for growth of material with different dopants. We show that the produced nanowire pn-junctions have excellent diode characteristics with a rectification ratio of >105, an ideality factor around 2, and very promising photoresponse. Using electron beam induced current and hyperspectral cathodoluminescence, we determined the location of the pn-junction and show that the grown nanowires have high doping levels, as well as electrical properties and diffusion lengths comparable to nanowires grown using metal organic vapor phase epitaxy. Our findings demonstrate that high-quality GaAs nanowire pn-junctions can be produced using a low-cost technique suitable for mass-production, paving the way for industrial-scale production of nanowire-based solar cells.
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| 69. |
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| 70. |
- Brynjólfsson, Siggeir Fannar, et al.
(författare)
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An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD.
- 2016
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Ingår i: Inflammatory bowel diseases. - 1536-4844. ; 22:8, s. 1803-11
-
Tidskriftsartikel (refereegranskat)abstract
- Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potent amplifier of inflammation. Recently, the antimicrobial peptide PGLYRP-1 was shown to be the ligand of TREM-1. Here, the ability of an anti-TREM-1 antibody to dampen the release of proinflammatory cytokines by colon lamina propria cells (LPCs) from patients with IBD was investigated and correlated with PGLYRP-1 levels.Biopsies from patients with ulcerative colitis (UC, n = 45) or Crohn's disease (CD, n = 26) were compared with those from individuals undergoing colonoscopy for other reasons (n = 17). TREM-1 expression was analyzed on myeloid cells by flow cytometry. Cell culture experiments with LPCs were used to analyze PGLYRP-1 and inflammatory cytokine levels and assess the effect of anti-TREM-1 on cytokine secretion.The frequency of TREM-1-expressing neutrophils and recruited macrophages was higher in inflamed than in noninflamed biopsies. The PGLYRP-1 level in inflamed tissue was higher than in noninflamed tissue; it was produced primarily by neutrophils, and its level correlated with the secretion of proinflammatory cytokines. Secretion of myeloperoxidase, tumor necrosis factor-α, interleukin-1β, and interleukin-8 by LPCs stimulated with the potent TREM-1 agonist consisting of PGLYRP-1 complexed with peptidoglycan was reduced in the presence of anti-TREM-1. Moreover, a blocking effect of anti-TREM-1 was apparent when LPCs from a subset of inflamed individuals with elevated PGLYRP-1 were stimulated with killed bacteria.An anti-TREM-1 antibody can dampen secretion of proinflammatory cytokines in inflamed patients with elevated PGLYRP-1. Moreover, PGLYRP-1 + myeloperoxidase is a potential biomarker for predicting the effect of anti-TREM-1 therapy.
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| 71. |
- Chen, X., et al.
(författare)
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A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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| 72. |
- Cheng, Susan, et al.
(författare)
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Distinct metabolomic signatures are associated with longevity in humans.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death.
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| 73. |
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| 74. |
- Fransson, Eleonor I, et al.
(författare)
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Job strain and the risk of stroke : an individual-participant data meta-analysis
- 2015
-
Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 46:2, s. 557-559
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Psychosocial stress at work has been proposed to be a risk factor for cardiovascular disease. However, its role as a risk factor for stroke is uncertain.METHODS: We conducted an individual-participant-data meta-analysis of 196 380 males and females from 14 European cohort studies to investigate the association between job strain, a measure of work-related stress, and incident stroke.RESULTS: In 1.8 million person-years at risk (mean follow-up 9.2 years), 2023 first-time stroke events were recorded. The age- and sex-adjusted hazard ratio for job strain relative to no job strain was 1.24 (95% confidence interval, 1.05;1.47) for ischemic stroke, 1.01 (95% confidence interval, 0.75;1.36) for hemorrhagic stroke, and 1.09 (95% confidence interval, 0.94;1.26) for overall stroke. The association with ischemic stroke was robust to further adjustment for socioeconomic status.CONCLUSION: Job strain may be associated with an increased risk of ischemic stroke, but further research is needed to determine whether interventions targeting job strain would reduce stroke risk beyond existing preventive strategies.
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| 75. |
- Giuffrida, L., et al.
(författare)
-
Nano and micro structured targets to modulate the spatial profile of laser driven proton beams
- 2017
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 12:3, s. article no C03040 -
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Tidskriftsartikel (refereegranskat)abstract
- Nano and micro structured thin (μ m-scale) foils were designed, fabricated and irradiated with the high intensity laser system operating at LLC (Lund Laser Centre, Sweden) in order to systematically study and improve the main proton beam parameters. Nano-spheres deposited on the front (laser irradiated) surface of a flat Mylar foil enabled a small enhancement of the maximum energy and number of the accelerated protons. Nano-spheres on the rear side allowed to modify the proton beam spatial profile. In particular, with nanospheres deposited on the rear of the target, the proton beam spatial homogeneity was clearly enhanced. Silicon nitride thin foils having micro grating structures (with different step dimensions) on the rear surface were also used as targets to influence the divergence of the proton beam and drastically change its shape through a sort of stretching effect. The target fabrication process used for the different target types is described, and representative experimental results are shown and discussed along with supporting 3D particle-in-cell simulations. © 2017 IOP Publishing Ltd and Sissa Medialab srl.
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| 76. |
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| 77. |
- Harris, Valerie M., et al.
(författare)
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Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome
- 2016
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Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 168, s. 25-29
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Tidskriftsartikel (refereegranskat)abstract
- Primary Sjogrens syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelters syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47)0(Y, p = 0.0012 by Fishers exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fishers exact test p = NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA. Published by Elsevier Inc.
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| 78. |
- Jelenkovic, A, et al.
(författare)
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Birth size and gestational age in opposite-sex twins as compared to same-sex twins: An individual-based pooled analysis of 21 cohorts
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 6300-
-
Tidskriftsartikel (refereegranskat)abstract
- It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95% CI −8 to −18 and −0.089 cm birth length; 95% CI −0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister.
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| 79. |
- Jelenkovic, A, et al.
(författare)
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Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts
- 2016
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Ingår i: Scientific reports. - London, United Kingdom : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28496-
-
Tidskriftsartikel (refereegranskat)abstract
- Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1–19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.
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| 80. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
-
Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
-
Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 81. |
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| 82. |
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| 83. |
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| 84. |
- Loley, C, et al.
(författare)
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No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 35278-
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.
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| 85. |
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| 86. |
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| 87. |
- Pradere, P., et al.
(författare)
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Lung transplantation for scleroderma lung disease: An international, multicenter, observational cohort study
- 2018
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 37:7, s. 903-911
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Due to its multisystemic nature, scleroderma is considered a relative contraindication to lung transplantation at many centers. However, recent studies suggest similar post-transplant outcomes in patients with scleroderma compared to those with other causes of interstitial lung disease (ILD). Furthermore, it remains unknown whether scleroderma-associated pulmonary arterial hypertension (PAH) influences post-transplant outcomes. Our objective in this study was to assess the indications, survival, and prognostic factors of lung or heart lung transplantation for scleroderma lung disease. METHODS: We retrospectively reviewed the data of 90 patients with scleroderma who underwent lung or heart lung transplantation between 1993 and 2016 at 14 European centers. International criteria were used to diagnose scleroderma. Pulmonary hypertension (PH) was diagnosed during right heart catheterization based on international guidelines. RESULTS: Survival rates after 1, 3, and 5 years were 81%, 68%, and 61%, respectively. By univariate analysis, borderline-significant associations with poorer survival were found for female gender (hazard ratio 2.11; 95% confidence interval [CI] 0.99 to 4.50; p = 0.05) and PAH as the reason for transplantation (hazard ratio 1.90; 95% CI 0.96 to 3.92; p = 0.06). When both these factors were present in combination, the risk of death was 3-fold that in males without PAH. The clinical and histologic presentation resembled veno-occlusive disease in 75% of patients with PAH. CONCLUSIONS: Post-transplant survival rates and freedom from chronic lung allograft dysfunction in patients with scleroderma were similar to those in patients with other reasons for lung transplantation. Female sex and PAH in combination was associated with lower survival. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.
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| 88. |
- Prentice, H. A., et al.
(författare)
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Patient demographic and surgical characteristics in anterior cruciate ligament reconstruction: a description of registries from six countries
- 2018
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective Findings from individual anterior cruciate ligament reconstruction (ACLR) registry studies are impactful, but how various registries from different countries compare with different patient populations and surgical techniques has not been described. We sought to describe six ACLR registry cohorts to understand variation across countries. Methods Five European registries and one US registry participated. For each registry, all primary ACLR registered between registry establishment through 31December 2014 were identified. Descriptive statistics included frequencies, proportions, medians and IQRs. Revision incidence rates following primary ACLR were computed. Results 101 125 ACLR were included: 21820 in Denmark, 300 in Luxembourg, 17556 in Norway, 30422 in Sweden, 2972 in the UK and 28055 in the US. In all six cohorts, males (range: 56.8%-72.4%) and soccer injuries (range: 14.1%-42.3%) were most common. European countries mostly used autografts (range: 93.7%-99.7%); allograft was most common in the US (39.9%). Interference screw was the most frequent femoral fixation in Luxembourg and the US (84.8% and 42.9%), and suspensory fixation was more frequent in the other countries (range: 43.9%-75.5%). Interference was the most frequent tibial fixation type in all six cohorts (range: 64.8%-98.2%). Three-year cumulative revision probabilities ranged from 2.8% to 3.7%. Conclusions Similarities in patient demographics and injury activity were observed between all cohorts of ACLR. However, graft and fixation choices differed. Revision rates were low. This work, including >100 000 ACLR, is the most comprehensive international description of contemporary practice to date.
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| 89. |
- Sellgren, C. M., et al.
(författare)
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A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:10, s. 1342-1350
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Tidskriftsartikel (refereegranskat)abstract
- Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant-associated with reduced SNX7 expression-to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1 beta and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder.
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| 90. |
- Sharma, Rohan, et al.
(författare)
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Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjogrens Syndrome
- 2017
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Ingår i: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 69:11, s. 2187-2192
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Sjogrens syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of similar to 10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. Methods. We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. Results. Among similar to 2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among similar to 2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in similar to 1 in 25,000-50,000 live female births, while partial triplications are even rarer. Conclusion. Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative.
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| 91. |
- Shungin, Dmitry, et al.
(författare)
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Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions
- 2017
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Ingår i: PLOS Genetics. - : Public Library Science. - 1553-7390 .- 1553-7404. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
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| 92. |
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| 93. |
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| 94. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 95. |
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| 96. |
- Tjellstrom, B, et al.
(författare)
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A Role for Bacteria in Celiac Disease?
- 2016
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Ingår i: Digestive diseases and sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 61:7, s. 2140-2140
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 97. |
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| 98. |
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| 99. |
- van der Laan, Sander W., et al.
(författare)
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Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study
- 2016
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:9, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
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| 100. |
- Virtanen, Marianna, et al.
(författare)
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Long working hours and depressive symptoms : systematic review and meta-analysis of published studies and unpublished individual participant data
- 2018
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Nordic Association of Occupational Safety and Health. - 0355-3140 .- 1795-990X. ; 44:3, s. 239-250
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Forskningsöversikt (refereegranskat)abstract
- Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published prospective cohort studies and included available cohorts with unpublished individual-participant data. We used a random-effects meta-analysis to calculate summary estimates across studies. Results We identified ten published cohort studies and included unpublished individual-participant data from 18 studies. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2=45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association in Europe (1.11, 95% CI 1.00-1.22), and no association in North America (0.97, 95% CI 0.70-1.34) or Australia (0.95, 95% CI 0.70-1.29). Differences by other characteristics were small. Conclusions This observational evidence suggests a moderate association between long working hours and onset of depressive symptoms in Asia and a small association in Europe.
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