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- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 3. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 9. |
- Björk Brämberg, Elisabeth, et al.
(författare)
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Increasing return-to-work among people on sick leave due to common mental disorders: design of a cluster-randomized controlled trial of a problem-solving intervention versus care-as-usual conducted in the Swedish primary health care system (PROSA)
- 2018
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Common mental disorders affect about one-third of the European working-age population and are one of the leading causes of sick leave in Sweden and other OECD countries. Besides the individual suffering, the costs for society are high. This paper describes the design of a study to evaluate a work-related, problem-solving intervention provided at primary health care centers for employees on sick leave due to common mental disorders. Methods: The study has a two-armed cluster randomized design in which the participating rehabilitation coordinators are randomized into delivering the intervention or providing care-as-usual. Employees on sick leave due to common mental disorders will be recruited by an independent research assistant. The intervention aims to improve the employee's return-to-work process by identifying problems perceived as hindering return-to-work and finding solutions. The rehabilitation coordinator facilitates a participatory approach, in which the employee and the employer together identify obstacles and solutions in relation to the work situation. The primary outcome is total number of sick leave days during the 18-month follow-up after inclusion. A long-term follow-up at 36 months is planned. Secondary outcomes are short-term sick leave (min. 2 weeks and max. 12 weeks), psychological symptoms, work ability, presenteeism and health related quality of life assessed at baseline, 6 and 12-month follow-up. Intervention fidelity, reach, dose delivered and dose received will be examined in a process evaluation. An economic evaluation will put health-related quality of life and sick leave in relation to costs from the perspectives of society and health care services. A parallel ethical evaluation will focus on the interventions consequences for patient autonomy, privacy, equality, fairness and professional ethos and integrity. Discussion: The study is a pragmatic trial which will include analyses of the intervention's effectiveness, and a process evaluation in primary health care settings. Methodological strengths and challenges are discussed, such as the risk of selection bias, contamination and detection bias. If the intervention shows promising results for return-to-work, the prospects are good for implementing the intervention in routine primary health care.
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| 10. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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