| 101. |
- Cesarini, David, et al.
(författare)
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Genotype-covariate interaction effects and the heritability of adult body mass index
- 2017
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 49:8, s. 1174-1181
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a worldwide epidemic, with major health and economic costs. Here we estimate heritability for body mass index (BMI) in 172,000 sibling pairs and 150,832 unrelated individuals and explore the contribution of genotype-covariate interaction effects at common SNP loci. We find evidence for genotype-age interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P = 4.83 × 10-18), which contributed 8.1% (1.4% s.e.) to BMI variation. Across eight self-reported lifestyle factors, including diet and exercise, we find genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03 × 10-5 and LRT = 30.80, P = 1.42 × 10-8), which contributed 4.0% (0.8% s.e.) to BMI variation. Bayesian association analysis suggests that BMI is highly polygenic, with 75% of the SNP heritability attributable to loci that each explain <0.01% of the phenotypic variance. Our findings imply that substantially larger sample sizes across ages and lifestyles are required to understand the full genetic architecture of BMI.
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| 102. |
- Clasen, Joanna L., et al.
(författare)
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Reproductive and hormonal factors and risk of renal cell carcinoma among women in the european prospective investigation into cancer and nutrition
- 2023
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:14, s. 15588-15600
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
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| 103. |
- Dai, Qile, et al.
(författare)
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OTTERS: a powerful TWAS framework leveraging summary-level reference data
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.
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| 104. |
- 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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| 105. |
- Gini, L., et al.
(författare)
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Part-Load Behaviour And Control Philosophy Of A Recuperated Supercritical Co2Cycle
- 2022
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Ingår i: Proceedings of the ASME Turbo Expo. - : American Society of Mechanical Engineers (ASME).
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Konferensbidrag (refereegranskat)abstract
- High efficiency, flexibility and competitive capital costs make supercritical CO2 (sCO2) systems a promising technology for renewable power generation in a low carbon energy scenario. Recently, innovative supercritical systems have been studied in the literature and proposed by DOE-NETL (STEP project) and a few projects in the EU Horizon 2020 program aiming to demonstrate supercritical CO2 Brayton power plants, promising superior techno-economic features than steam cycles particularly at high temperatures. The H2020 SOLARSCO2OL project1, which started in 2020, is building the first European MW-scale sCO2 demonstration plant and has been specifically tailored for Concentrating Solar Power (CSP) applications. This paper presents the first offdesign analysis of such a demonstrator, which is based on a simply recuperated sCO2 cycle. The part-load analysis ranged from 50% of nominal up to a 105% peak load, discussing the impact on compressor and turbine operating conditions. The whole system dynamic model has been developed in TRANSEO MATLAB® environment. Full operational envelop has been determined considering cycle main constraints, such as maximum turbine inlet temperature and minimum pressure at compressor inlet. The off-design performance analysis highlights the most relevant relationships among the main part-load regulating parameters, namely mass flow rate, total mass in the loop, and available heat source. The results show specific features of different control approaches, discussing the pros and cons of each solution, considering also its upscale towards commercial applications. In particular, the analysis shows that at 51% of load an efficiency decrease of 20% is expected.
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| 106. |
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| 107. |
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| 108. |
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| 109. |
- Kimberling, William J., et al.
(författare)
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Gene mapping of Usher syndrome type IIa : localization of the gene to a 2.1-cM segment on chromosome 1q41
- 1995
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 56:1, s. 216-223
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor β2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.
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| 110. |
- Kimberling, W. J., et al.
(författare)
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Genetic studies of Usher syndrome
- 1991
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 630:1, s. 167-175
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Tidskriftsartikel (refereegranskat)
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