928 results on '"Gustafsson,S"'
Search Results
2. Further development of the reflective practice questionnaire.
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Rogers, SL, Van Winkle, L, Michels, N, Lucas, C, Ziada, H, Da Silva, EJ, Jotangia, A, Gabrielsson, S, Gustafsson, S, Priddis, L, Rogers, SL, Van Winkle, L, Michels, N, Lucas, C, Ziada, H, Da Silva, EJ, Jotangia, A, Gabrielsson, S, Gustafsson, S, and Priddis, L
- Abstract
BACKGROUND: This article provides an update of the Reflective Practice Questionnaire (RPQ). The original RPQ consisted of 40-items with 10-sub-scales. In this article, the RPQ is streamlined into a 10-item single reflective practice construct, and a 30-item extended version that includes additional sub-scales of confidence, uncertainty/stress, and work satisfaction. METHODS: A total of 501 university students filled out an online questionnaire that contained the original Reflective Practice Questionnaire, and two general measures of reflection: The Self-Reflection and Insight Scale, and the Rumination-Reflection Questionnaire. RESULTS: Based on factor analysis, the RPQ was streamlined into a brief 10-item version, and an extended 30-item version. Small positive correlations were found between the RPQ reflective practice measure and the two measures of general reflection, providing discriminant validity evidence for the RPQ. The RPQ was found to be sensitive to differences among industries, whereas the general measures of reflection were not. Average reflective practice scores were higher for health and education industries compared to retail and food/accommodation industries.
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- 2024
3. RWD168 Epidemiology of Respiratory Syncytial Virus in Uppsala and Stockholm: A Population-Based Study
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Varghese, N.E., primary, He, J., additional, Gustafsson, S., additional, Weber, K., additional, Cars, T., additional, Hernandez-Pastor, L., additional, Qu, Y., additional, and Sundström, J., additional
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- 2023
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4. Interconnectivity imaged in three dimensions: Nano-particulate silica-hydrogel structure revealed using electron tomography
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Hamngren Blomqvist, C., Gebäck, T., Altskär, A., Hermansson, A.-M., Gustafsson, S., Lorén, N., and Olsson, E.
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- 2017
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5. Minor positive effects of health-promoting senior meetings for older community-dwelling persons on loneliness, social network, and social support
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Gustafsson S, Berglund H, Faronbi J, Barenfeld E, and Ottenvall Hammar I
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Aged ,Quality of Life ,Health promotion ,Prevention ,Group intervention ,Evaluation studies ,Geriatrics ,RC952-954.6 - Abstract
Susanne Gustafsson,1,2 Helene Berglund,1,3 Joel Faronbi,1,4 Emmelie Barenfeld,1,2,5 Isabelle Ottenvall Hammar1,2 1Frail Elderly Research Support Group (FRESH), Institute of Neuroscience and Physiology, Sahlgrenska Academy at Gothenburg University, 2Gothenburg University Centre for Ageing and Health (AgeCap), 3Institute of Health and Care Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; 4Department of Nursing Science, College of Health Science, Obafemi Awolowo University, Ile-Ife, Nigeria; 5Department of Occupational Therapy and Physiotherapy, Sahlgrenska University Hospital, Gothenburg, Sweden Objective: The aim of this study was to evaluate the 1-year effect of the health-promoting intervention “senior meetings” for older community-dwelling persons regarding loneliness, social network, and social support.Methods: Secondary analysis of data was carried out from two randomized controlled studies: Elderly Persons in the Risk Zone and Promoting Aging Migrants’ Capabilities. Data from 416 participants who attended the senior meetings and the control group at baseline and the 1-year follow-up in the respective studies were included. Data were aggregated and analyzed with chi-square test and odds ratio (OR) to determine the intervention effect.Results: The senior meetings had a positive effect on social support regarding someone to turn to when in need of advice and backing (OR 1.72, p=0.01). No positive intervention effect could be identified for loneliness, social network, or other aspects of social support.Conclusion: Health-promoting senior meetings for older community-dwelling persons have a minor positive effect on social support. The senior meetings might benefit from a revision to reinforce content focused on loneliness, social network, and social support. However, the modest effect could also depend on the lack of accessible social resources to meet participants’ identified needs, a possible hindrance for a person’s capability. This makes it necessary to conduct further research to evaluate the effect of the senior meetings and other health-promoting initiatives on social aspects of older community-dwelling people’s lives, since these aspects are of high importance for life satisfaction and well-being in old age. Keywords: aged, quality of life, health promotion, prevention, group intervention, evaluation studies
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- 2017
6. Paralegals and the casualisation of legal labour markets
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Abel, RL, Hammerslev, O, Sommerlad, H, Ulrike, U, Hersant, J, Holvast, N, Verzelloni, L, Gustafsson, S, Sandefur, R, Clarke, T, Sommerlad H., Hersant J., Holvast N., Verzelloni L., Gustafsson S., Sandefur R., Clarke T., Abel, RL, Hammerslev, O, Sommerlad, H, Ulrike, U, Hersant, J, Holvast, N, Verzelloni, L, Gustafsson, S, Sandefur, R, Clarke, T, Sommerlad H., Hersant J., Holvast N., Verzelloni L., Gustafsson S., Sandefur R., and Clarke T.
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- 2022
7. Controller Hierarchies for Efficient Virtual Ergonomic Assessments of Manual Assembly Sequences
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Mårdberg, P., Yan, Y., Bohlin, R., Delfs, N., Gustafsson, S., and Carlson, J.S.
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- 2016
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8. Author Correction: The power of genetic diversity in genome-wide association studies of lipids (Nature, (2021), 600, 7890, (675-679), 10.1038/s41586-021-04064-3)
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Graham, S.E. Clarke, S.L. Wu, K.-H.H. Kanoni, S. Zajac, G.J.M. Ramdas, S. Surakka, I. Ntalla, I. Vedantam, S. Winkler, T.W. Locke, A.E. Marouli, E. Hwang, M.Y. Han, S. Narita, A. Choudhury, A. Bentley, A.R. Ekoru, K. Verma, A. Trivedi, B. Martin, H.C. Hunt, K.A. Hui, Q. Klarin, D. Zhu, X. Thorleifsson, G. Helgadottir, A. Gudbjartsson, D.F. Holm, H. Olafsson, I. Akiyama, M. Sakaue, S. Terao, C. Kanai, M. Zhou, W. Brumpton, B.M. Rasheed, H. Ruotsalainen, S.E. Havulinna, A.S. Veturi, Y. Feng, Q.P. Rosenthal, E.A. Lingren, T. Pacheco, J.A. Pendergrass, S.A. Haessler, J. Giulianini, F. Bradford, Y. Miller, J.E. Campbell, A. Lin, K. Millwood, I.Y. Hindy, G. Rasheed, A. Faul, J.D. Zhao, W. Weir, D.R. Turman, C. Huang, H. Graff, M. Mahajan, A. Brown, M.R. Zhang, W. Yu, K. Schmidt, E.M. Pandit, A. Gustafsson, S. Yin, X. Luan, J. Zhao, J.-H. Matsuda, F. Jang, H.-M. Yoon, K. Medina-Gomez, C. Pitsillides, A. Hottenga, J.J. Willemsen, G. Wood, A.R. Ji, Y. Gao, Z. Haworth, S. Mitchell, R.E. Chai, J.F. Aadahl, M. Yao, J. Manichaikul, A. Warren, H.R. Ramirez, J. Bork-Jensen, J. Kårhus, L.L. Goel, A. Sabater-Lleal, M. Noordam, R. Sidore, C. Fiorillo, E. McDaid, A.F. Marques-Vidal, P. Wielscher, M. Trompet, S. Sattar, N. Møllehave, L.T. Thuesen, B.H. Munz, M. Zeng, L. Huang, J. Yang, B. Poveda, A. Kurbasic, A. Lamina, C. Forer, L. Scholz, M. Galesloot, T.E. Bradfield, J.P. Daw, E.W. Zmuda, J.M. Mitchell, J.S. Fuchsberger, C. Christensen, H. Brody, J.A. Feitosa, M.F. Wojczynski, M.K. Preuss, M. Mangino, M. Christofidou, P. Verweij, N. Benjamins, J.W. Engmann, J. Kember, R.L. Slieker, R.C. Lo, K.S. Zilhao, N.R. Le, P. Kleber, M.E. Delgado, G.E. Huo, S. Ikeda, D.D. Iha, H. Yang, J. Liu, J. Leonard, H.L. Marten, J. Schmidt, B. Arendt, M. Smyth, L.J. Cañadas-Garre, M. Wang, C. Nakatochi, M. Wong, A. Hutri-Kähönen, N. Sim, X. Xia, R. Huerta-Chagoya, A. Fernandez-Lopez, J.C. Lyssenko, V. Ahmed, M. Jackson, A.U. Yousri, N.A. Irvin, M.R. Oldmeadow, C. Kim, H.-N. Ryu, S. Timmers, P.R.H.J. Arbe and Graham, S.E. Clarke, S.L. Wu, K.-H.H. Kanoni, S. Zajac, G.J.M. Ramdas, S. Surakka, I. Ntalla, I. Vedantam, S. Winkler, T.W. Locke, A.E. Marouli, E. Hwang, M.Y. Han, S. Narita, A. Choudhury, A. Bentley, A.R. Ekoru, K. Verma, A. Trivedi, B. Martin, H.C. Hunt, K.A. Hui, Q. Klarin, D. Zhu, X. Thorleifsson, G. Helgadottir, A. Gudbjartsson, D.F. Holm, H. Olafsson, I. Akiyama, M. Sakaue, S. Terao, C. Kanai, M. Zhou, W. Brumpton, B.M. Rasheed, H. Ruotsalainen, S.E. Havulinna, A.S. Veturi, Y. Feng, Q.P. Rosenthal, E.A. Lingren, T. Pacheco, J.A. Pendergrass, S.A. Haessler, J. Giulianini, F. Bradford, Y. Miller, J.E. Campbell, A. Lin, K. Millwood, I.Y. Hindy, G. Rasheed, A. Faul, J.D. Zhao, W. Weir, D.R. Turman, C. Huang, H. Graff, M. Mahajan, A. Brown, M.R. Zhang, W. Yu, K. Schmidt, E.M. Pandit, A. Gustafsson, S. Yin, X. Luan, J. Zhao, J.-H. Matsuda, F. Jang, H.-M. Yoon, K. Medina-Gomez, C. Pitsillides, A. Hottenga, J.J. Willemsen, G. Wood, A.R. Ji, Y. Gao, Z. Haworth, S. Mitchell, R.E. Chai, J.F. Aadahl, M. Yao, J. Manichaikul, A. Warren, H.R. Ramirez, J. Bork-Jensen, J. Kårhus, L.L. Goel, A. Sabater-Lleal, M. Noordam, R. Sidore, C. Fiorillo, E. McDaid, A.F. Marques-Vidal, P. Wielscher, M. Trompet, S. Sattar, N. Møllehave, L.T. Thuesen, B.H. Munz, M. Zeng, L. Huang, J. Yang, B. Poveda, A. Kurbasic, A. Lamina, C. Forer, L. Scholz, M. Galesloot, T.E. Bradfield, J.P. Daw, E.W. Zmuda, J.M. Mitchell, J.S. Fuchsberger, C. Christensen, H. Brody, J.A. Feitosa, M.F. Wojczynski, M.K. Preuss, M. Mangino, M. Christofidou, P. Verweij, N. Benjamins, J.W. Engmann, J. Kember, R.L. Slieker, R.C. Lo, K.S. Zilhao, N.R. Le, P. Kleber, M.E. Delgado, G.E. Huo, S. Ikeda, D.D. Iha, H. Yang, J. Liu, J. Leonard, H.L. Marten, J. Schmidt, B. Arendt, M. Smyth, L.J. Cañadas-Garre, M. Wang, C. Nakatochi, M. Wong, A. Hutri-Kähönen, N. Sim, X. Xia, R. Huerta-Chagoya, A. Fernandez-Lopez, J.C. Lyssenko, V. Ahmed, M. Jackson, A.U. Yousri, N.A. Irvin, M.R. Oldmeadow, C. Kim, H.-N. Ryu, S. Timmers, P.R.H.J. Arbe
- Abstract
Correction to: Nature Published online 9 December 2021 In the version of this article initially published, Noha A. Yousri (Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and Department of Computer and Systems Engineering, Alexandria University, Egypt) and Steven C. Hunt (Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA and Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar) were not included in the author list. In addition, Hieab H. H. Adams (Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands and Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands) was shown with an incorrect second affiliation in the HTML and PDF versions of the article. Finally, in the HTML version, Cristen J. Willer was mistakenly listed with an extra affiliation (Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia). The authors and affiliations have been corrected in the HTML and PDF versions of the article. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.
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- 2023
9. Relativistic CI Calculations of Spectroscopic Data for the 2p6 and 2p53l Configurations in Ne-like Ions between Mg III and Kr XXVII
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JÖNSSON, P., BENGTSSON, P., EKMAN, J., GUSTAFSSON, S., KARLSSON, L. B., GAIGALAS, Gediminas, FISCHER, C. Froese, KATO, Daiji, MURAKAMI, Izumi, SAKAUE, Hiroyuki A., HARA, Hirohisa, WATANABE, T., NAKAMURA, N., YAMAMOTO, N., JÖNSSON, P., BENGTSSON, P., EKMAN, J., GUSTAFSSON, S., KARLSSON, L. B., GAIGALAS, Gediminas, FISCHER, C. Froese, KATO, Daiji, MURAKAMI, Izumi, SAKAUE, Hiroyuki A., HARA, Hirohisa, WATANABE, T., NAKAMURA, N., and YAMAMOTO, N.
- Abstract
Energies, E1, M1, E2, M2 transition rates, oscillator strengths, and lifetimes from relativistic configuration interaction calculations are reported for the states of the 2p6, 2p53s, 2p53p, and 2p53d, configurations in all Ne-like ions between Mg III and Kr XXVII. Core-valence and core-core correlation effects are accounted for through SD-expansions to increasing sets of active orbitals. The Breit interaction and leading QED effects are included as perturbations. The results are compared with experiments and other recent benchmark calculations. In Mg III, Al IV, Si V, P VI, S VII, and Ar IX, for which experimental energies are known to high accuracy, the mean error in the calculated energies is only 0.011%.
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- 2023
10. Loci for insulin processing and secretion provide insight into type 2 diabetes risk
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Broadaway, K. A. (K. Alaine), Yin, X. (Xianyong), Williamson, A. (Alice), Parsons, V. A. (Victoria A.), Wilson, E. P. (Emma P.), Moxley, A. H. (Anne H.), Vadlamudi, S. (Swarooparani), Varshney, A. (Arushi), Jackson, A. U. (Anne U.), Ahuja, V. (Vasudha), Bornstein, S. R. (Stefan R.), Corbin, L. J. (Laura J.), Delgado, G. E. (Graciela E.), Dwivedi, O. P. (Om P.), Silva, L. F. (Lilian Fernandes), Frayling, T. M. (Timothy M.), Grallert, H. (Harald), Gustafsson, S. (Stefan), Hakaste, L. (Liisa), Hammar, U. (Ulf), Herder, C. (Christian), Herrmann, S. (Sandra), Hojlund, K. (Kurt), Hughes, D. A. (David A.), Kleber, M. E. (Marcus E.), Lindgren, C. M. (Cecilia M.), Liu, C.-T. (Ching-Ti), Luan, J. (Jian'an), Malmberg, A. (Anni), Moissl, A. P. (Angela P.), Morris, A. P. (Andrew P.), Perakakis, N. (Nikolaos), Peters, A. (Annette), Petrie, J. R. (John R.), Roden, M. (Michael), Schwarz, P. E. (Peter E. H.), Sharma, S. (Sapna), Silveira, A. (Angela), Strawbridge, R. J. (Rona J.), Tuomi, T. (Tiinamaija), Wood, A. R. (Andrew R.), Wu, P. (Peitao), Zethelius, B. (Bjorn), Baldassarre, D. (Damiano), Eriksson, J. G. (Johan G.), Fall, T. (Tove), Florez, J. C. (Jose C.), Fritsche, A. (Andreas), Gigante, B. (Bruna), Hamsten, A. (Anders), Kajantie, E. (Eero), Laakso, M. (Markku), Lahti, J. (Jari), Lawlor, D. A. (Deborah A.), Lind, L. (Lars), Maerz, W. (Winfried), Meigs, J. B. (James B.), Sundstrom, J. (Johan), Timpson, N. J. (Nicholas J.), Wagner, R. (Robert), Walker, M. (Mark), Wareham, N. J. (Nicholas J.), Watkins, H. (Hugh), Barroso, I. (Ines), O'Rahilly, S. (Stephen), Grarup, N. (Niels), Parker, S. C. (Stephen CJ.), Boehnke, M. (Michael), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Mohlke, K. L. (Karen L.), Broadaway, K. A. (K. Alaine), Yin, X. (Xianyong), Williamson, A. (Alice), Parsons, V. A. (Victoria A.), Wilson, E. P. (Emma P.), Moxley, A. H. (Anne H.), Vadlamudi, S. (Swarooparani), Varshney, A. (Arushi), Jackson, A. U. (Anne U.), Ahuja, V. (Vasudha), Bornstein, S. R. (Stefan R.), Corbin, L. J. (Laura J.), Delgado, G. E. (Graciela E.), Dwivedi, O. P. (Om P.), Silva, L. F. (Lilian Fernandes), Frayling, T. M. (Timothy M.), Grallert, H. (Harald), Gustafsson, S. (Stefan), Hakaste, L. (Liisa), Hammar, U. (Ulf), Herder, C. (Christian), Herrmann, S. (Sandra), Hojlund, K. (Kurt), Hughes, D. A. (David A.), Kleber, M. E. (Marcus E.), Lindgren, C. M. (Cecilia M.), Liu, C.-T. (Ching-Ti), Luan, J. (Jian'an), Malmberg, A. (Anni), Moissl, A. P. (Angela P.), Morris, A. P. (Andrew P.), Perakakis, N. (Nikolaos), Peters, A. (Annette), Petrie, J. R. (John R.), Roden, M. (Michael), Schwarz, P. E. (Peter E. H.), Sharma, S. (Sapna), Silveira, A. (Angela), Strawbridge, R. J. (Rona J.), Tuomi, T. (Tiinamaija), Wood, A. R. (Andrew R.), Wu, P. (Peitao), Zethelius, B. (Bjorn), Baldassarre, D. (Damiano), Eriksson, J. G. (Johan G.), Fall, T. (Tove), Florez, J. C. (Jose C.), Fritsche, A. (Andreas), Gigante, B. (Bruna), Hamsten, A. (Anders), Kajantie, E. (Eero), Laakso, M. (Markku), Lahti, J. (Jari), Lawlor, D. A. (Deborah A.), Lind, L. (Lars), Maerz, W. (Winfried), Meigs, J. B. (James B.), Sundstrom, J. (Johan), Timpson, N. J. (Nicholas J.), Wagner, R. (Robert), Walker, M. (Mark), Wareham, N. J. (Nicholas J.), Watkins, H. (Hugh), Barroso, I. (Ines), O'Rahilly, S. (Stephen), Grarup, N. (Niels), Parker, S. C. (Stephen CJ.), Boehnke, M. (Michael), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), and Mohlke, K. L. (Karen L.)
- Abstract
Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value <5×10⁻⁸), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6‐3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6‐3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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- 2023
11. Further development of the Reflective Practice Questionnaire
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Rogers, SL, Van Winkle, L, Michels, N, Lucas, C, Ziada, H, Da Silva, E, Jotangia, A, Gabrielsson, S, Gustafsson, S, Priddis, L, Rogers, SL, Van Winkle, L, Michels, N, Lucas, C, Ziada, H, Da Silva, E, Jotangia, A, Gabrielsson, S, Gustafsson, S, and Priddis, L
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- 2023
12. Markers of imminent myocardial infarction
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Sundstrom, J, primary, Lampa, E, additional, Jensevik Eriksson, K, additional, Ganna, A, additional, Svennblad, B, additional, and Gustafsson, S, additional
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- 2023
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13. Usefulness of heart failure categories based on left ventricular ejection fraction
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Christersson, M, primary, Gustafsson, S, additional, Lampa, E, additional, Almstedt, M, additional, Cars, T, additional, Arefalk, G, additional, and Sundstrom, J, additional
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- 2023
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14. Sustainable Energy and Climate Strategies: lessons from planning processes in five municipalities
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Fenton, P., Gustafsson, S., Ivner, J., and Palm, J.
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- 2015
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15. Relativistic CI calculations of spectroscopic data for the [formula omitted] and [formula omitted] configurations in Ne-like ions between Mg III and Kr XXVII
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Jönsson, P., Bengtsson, P., Ekman, J., Gustafsson, S., Karlsson, L.B., Gaigalas, G., Froese Fischer, C., Kato, D., Murakami, I., Sakaue, H.A., Hara, H., Watanabe, T., Nakamura, N., and Yamamoto, N.
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- 2014
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16. Evaluating reflective practice groups in a mental health context: Swedish translation and psychometric evaluation of the clinical supervision evaluation questionnaire
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Gabrielsson, S., Engström, Å., and Gustafsson, S.
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- 2019
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17. Paralegals and the casualisation of legal labour markets
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Sommerlad H., Hersant J., Holvast N., Verzelloni L., Gustafsson S., Sandefur R., Clarke T., Abel, RL, Hammerslev, O, Sommerlad, H, Ulrike, U, Hersant, J, Holvast, N, Verzelloni, L, Gustafsson, S, Sandefur, R, and Clarke, T
- Subjects
paralegal ,SPS/09 - SOCIOLOGIA DEI PROCESSI ECONOMICI E DEL LAVORO ,legal profession ,casualisation ,legal labour market - Published
- 2022
18. Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
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de Peppo GM, Agheli H, Karlsson C, Ekström K, Brisby H, Lennerås M, Gustafsson S, Sjövall P, Johansson A, Olsson E, Lausmaa J, Thomsen P, and Petronis S
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Medicine (General) ,R5-920 - Abstract
Giuseppe Maria de Peppo,1–3 Hossein Agheli,2,3 Camilla Karlsson,2,3 Karin Ekström,2,3 Helena Brisby,3,4 Maria Lennerås,2,3 Stefan Gustafsson,3,5 Peter Sjövall,3,5,6 Anna Johansson,2,3 Eva Olsson,3,5 Jukka Lausmaa,3,6 Peter Thomsen,2,3 Sarunas Petronis3,6 1The New York Stem Cell Foundation Research Institute, New York, NY, USA; 2Department of Biomaterials, Sahlgrenska Academy, University of Gothenburg, 3BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, 4Department of Orthopaedics, Sahlgrenska Academy, University of Gothenburg, 5Applied Physics, Chalmers University of Technology, Göteborg, Sweden; 6Chemistry, Materials and Surfaces, SP Technical Research Institute of Sweden, Borås, Sweden Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role in the osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenic differentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration. Keywords: colloidal lithography, nanotopography, human mesenchymal stem cells, cell proliferation, osteogenic differentiation, mineralization, implantable materials
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- 2014
19. Long-term assessment and target achievement of LDL-C and systolic blood pressure in primary care after acute coronary syndrome
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Schubert, J, primary, Svensson, M, additional, Denstedt, G, additional, Johnston, N, additional, Cars, T, additional, Gustafsson, S, additional, Schalin, L, additional, and Hagstrom, E, additional
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- 2022
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20. Low-density lipoprotein cholesterol reduction with evolocumab and its use in clinical practice: evidence from Swedish national register data
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Svensson, M K, primary, James, S, additional, Ravn-Fischer, A, additional, Pantev, E, additional, Villa, G, additional, Schalin, L, additional, Cars, T, additional, Gustafsson, S, additional, and Hagstrom, E, additional
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- 2022
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21. Macroinvertebrate colonization of a nature-like fishway: The effects of adding habitat heterogeneity
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Gustafsson, S., Österling, M., Skurdal, J., Schneider, L.D., and Calles, O.
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- 2013
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22. Perceptions of participating in high-intensity functional exercise among older people dependent in activities of daily living (ADL)
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Lindelöf, N., Rosendahl, E., Gustafsson, S., Nygaard, J., Gustafson, Y., and Nyberg, L.
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- 2013
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23. Targeted proteomic analysis of habitual coffee consumption
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Cornelis, M. C., Gustafsson, S., Ärnlöv, J., Elmståhl, S., Söderberg, S., Sundström, J., Michaëlsson, K., Lind, L., and Ingelsson, E.
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- 2018
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24. Reinserting professional work(ers) into organizations
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Ahuja, S, Goto, M, Gustafsson, S, Muzio, D, Noury, L, Pemer, F, Sandholtz, K, and Sturdy, A
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- 2022
25. Thermal conductivity vs depth profiling using the hot disk technique—Analysis of anisotropic, inhomogeneous structures.
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Sizov, A., Mihiretie, B., Ma, Y., Gustafsson, S. E., and Gustavsson, M.
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THERMAL conductivity ,DEPTH profiling ,TEST methods ,ANISOTROPY - Abstract
A recently developed method for analyzing the thermal conductivity vs depth variation near a sample surface has been extended to include inhomogeneous samples with anisotropy. If not considered, the anisotropy ratio in the sample structure can distort the depth-position data of the original test method. The anisotropy ratio is introduced in the original computational scheme in order to improve the depth-position estimations for inhomogeneous structures with anisotropy. The proposed approach has been tested in experiments and shown to improve depth position mapping. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
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26. Genetic landscape of the ACE2 coronavirus receptor
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Yang, Z, MacDonald-Dunlop, E, Chen, J, Zhai, R, Li, T, Richmond, A, Klaric, L, Pirastu, N, Ning, Z, Zheng, C, Wang, Y, Huang, T, He, Y, Guo, H, Ying, K, Gustafsson, S, Prins, B, Ramisch, A, Dermitzakis, ET, Png, G, Eriksson, N, Haessler, J, Hu, X, Zanetti, D, Boutin, T, Hwang, S-J, Wheeler, E, Pietzner, M, Raffield, LM, Kalnapenkis, A, Peters, JE, Viñuela, A, Gilly, A, Elmståhl, S, Dedoussis, G, Petrie, JR, Polašek, O, Folkersen, L, Chen, Y, Yao, C, Võsa, U, Pairo-Castineira, E, Clohisey, S, Bretherick, AD, Rawlik, K, Esko, T, Enroth, S, Johansson, Å, Gyllensten, U, Langenberg, C, Levy, D, Hayward, C, Assimes, TL, Kooperberg, C, Manichaikul, AW, Siegbahn, A, Wallentin, L, Lind, L, Zeggini, E, Schwenk, JM, Butterworth, AS, Michaëlsson, K, Pawitan, Y, Joshi, PK, Baillie, JK, Mälarstig, A, Reiner, AP, Wilson, JF, Shen, X, and GenOMICC Consortium and the IMI-DIRECT Consortium
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ANGIOTENSIN-CONVERTING ENZYME ,Cardiac & Cardiovascular Systems ,GenOMICC Consortium† ,DATABASE ,COVID ,genetic ,analysis ,ALPHA-1-ANTITRYPSIN DEFICIENCY ,1117 Public Health and Health Services ,angiotensin-converting enzyme 2 ,Physiology (medical) ,Humans ,Cardiac and Cardiovascular Systems ,1102 Cardiorespiratory Medicine and Haematology ,Medicinsk genetik ,RISK ,Kardiologi ,Science & Technology ,SARS-CoV-2 ,COVID-19 ,IMI-DIRECT Consortium† ,1103 Clinical Sciences ,COVID-19/genetics ,cardiovascular diseases ,Angiotensin-Converting Enzyme 2/genetics ,Cross-Sectional Studies ,Peripheral Vascular Disease ,Cardiovascular System & Hematology ,Cardiovascular System & Cardiology ,TRIAL ,Cardiology and Cardiovascular Medicine ,Medical Genetics ,Life Sciences & Biomedicine ,hormones, hormone substitutes, and hormone antagonists ,Genome-Wide Association Study ,Receptors, Coronavirus - Abstract
Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood. Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics–based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data. Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis–protein quantitative trait loci–based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10–2.42]; P =0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05–2.21]; P =0.03), and infection (odds ratio, 1.60 [95% CI, 1.08–2.37]; P =0.02). Tissue- and cell type–specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells. Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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- 2022
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27. How to deal with sociocultural pressures in daily life: reflections of adolescent girls suffering from eating disorders
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Aila Gustafsson S, Edlund B, Davén J, Kjellin L, and Norring C
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Medicine (General) ,R5-920 - Abstract
Sanna Aila Gustafsson1, Birgitta Edlund2, Josefine Davén1, Lars Kjellin1, Claes Norring31Psychiatric Research Centre, Örebro University, School of Health and Medical Sciences, Örebro, Sweden; 2Department of Public Health and Caring Sciences, University of Uppsala, Uppsala, Sweden; 3Center for Psychiatry Research, Karolinska Institute, and Stockholm Center for Eating Disorders, Stockholm, SwedenAbstract: Adolescent girls with eating disorders experience unattainable and contradictory expectations in daily life, which create stress and negatively affect their self-evaluation. Disordered eating may function as a way of seeking control and consistency. In order to make progress in the understanding of eating disorders, the aim of this study was to describe how adolescent girls with eating disorders reflect upon ways of dealing with sociocultural pressures in daily life. Eighteen interviews with girls aged 15–19 years were analyzed using a phenomenographic approach. The results were summarized into three conceptions: ‘Striving to be oneself" (conception A) was described as the most desirable, but also the hardest. "Adapting to various situations’ (conception B) was used without much reflection, as long as it worked, but when this way of dealing with everyday expectations was unsuccessful it was evaluated negatively. "Presenting oneself in a positive light" (conception C) was described negatively even when it was successful. Within these conceptions, the participants described various strategies that could be used more or less effectively depending on the circumstances. A common theme was their difficulties in finding a balance between trying harder to live up to perceived expectations from others on one hand, and trying to accept the situation as it was, without trying to change themselves or the situation, on the other hand. The participants believed that their eating disorder was partly a result of being unable to deal with sociocultural pressures in an effective way, and they experienced a conflict between societal values of being assertive and values of being interpersonally oriented. Implications for treatment are discussed.Keywords: mental health, qualitative, phenomenography
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- 2011
28. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
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Ramdas, S. Judd, J. Graham, S.E. Kanoni, S. Wang, Y. Surakka, I. Wenz, B. Clarke, S.L. Chesi, A. Wells, A. Bhatti, K.F. Vedantam, S. Winkler, T.W. Locke, A.E. Marouli, E. Zajac, G.J.M. Wu, K.-H.H. Ntalla, I. Hui, Q. Klarin, D. Hilliard, A.T. Wang, Z. Xue, C. Thorleifsson, G. Helgadottir, A. Gudbjartsson, D.F. Holm, H. Olafsson, I. Hwang, M.Y. Han, S. Akiyama, M. Sakaue, S. Terao, C. Kanai, M. Zhou, W. Brumpton, B.M. Rasheed, H. Havulinna, A.S. Veturi, Y. Pacheco, J.A. Rosenthal, E.A. Lingren, T. Feng, Q. Kullo, I.J. Narita, A. Takayama, J. Martin, H.C. Hunt, K.A. Trivedi, B. Haessler, J. Giulianini, F. Bradford, Y. Miller, J.E. Campbell, A. Lin, K. Millwood, I.Y. Rasheed, A. Hindy, G. Faul, J.D. Zhao, W. Weir, D.R. Turman, C. Huang, H. Graff, M. Choudhury, A. Sengupta, D. Mahajan, A. Brown, M.R. Zhang, W. Yu, K. Schmidt, E.M. Pandit, A. Gustafsson, S. Yin, X. Luan, J. Zhao, J.-H. Matsuda, F. Jang, H.-M. Yoon, K. Medina-Gomez, C. Pitsillides, A. Hottenga, J.J. Wood, A.R. Ji, Y. Gao, Z. Haworth, S. Mitchell, R.E. Chai, J.F. Aadahl, M. Bjerregaard, A.A. Yao, J. Manichaikul, A. Lee, W.-J. Hsiung, C.A. Warren, H.R. Ramirez, J. Bork-Jensen, J. Kårhus, L.L. Goel, A. Sabater-Lleal, M. Noordam, R. Mauro, P. Matteo, F. McDaid, A.F. Marques-Vidal, P. Wielscher, M. Trompet, S. Sattar, N. Møllehave, L.T. Munz, M. Zeng, L. Huang, J. Yang, B. Poveda, A. Kurbasic, A. Schönherr, S. Forer, L. Scholz, M. Galesloot, T.E. Bradfield, J.P. Ruotsalainen, S.E. Daw, E.W. Zmuda, J.M. Mitchell, J.S. Fuchsberger, C. Christensen, H. Brody, J.A. Le, P. Feitosa, M.F. Wojczynski, M.K. Hemerich, D. Preuss, M. Mangino, M. Christofidou, P. Verweij, N. Benjamins, J.W. Engmann, J. Noah, T.L. Verma, A. Slieker, R.C. Lo, K.S. Zilhao, N.R. Kleber, M.E. Delgado, G.E. Huo, S. Ikeda, D.D. Iha, H. Yang, J. Liu, J. Demirkan, A. Leonard, H.L. Marten, J. Emmel, C. Schmidt, B. Smyth, L.J. Cañadas-Garre, M. Wang, C. Nakatochi, M. Wong, A. Hutri-Kähönen, N. Sim, X. Xia, R. Huerta-Chagoya, A. Fernandez-Lopez, J.C. Ly and Ramdas, S. Judd, J. Graham, S.E. Kanoni, S. Wang, Y. Surakka, I. Wenz, B. Clarke, S.L. Chesi, A. Wells, A. Bhatti, K.F. Vedantam, S. Winkler, T.W. Locke, A.E. Marouli, E. Zajac, G.J.M. Wu, K.-H.H. Ntalla, I. Hui, Q. Klarin, D. Hilliard, A.T. Wang, Z. Xue, C. Thorleifsson, G. Helgadottir, A. Gudbjartsson, D.F. Holm, H. Olafsson, I. Hwang, M.Y. Han, S. Akiyama, M. Sakaue, S. Terao, C. Kanai, M. Zhou, W. Brumpton, B.M. Rasheed, H. Havulinna, A.S. Veturi, Y. Pacheco, J.A. Rosenthal, E.A. Lingren, T. Feng, Q. Kullo, I.J. Narita, A. Takayama, J. Martin, H.C. Hunt, K.A. Trivedi, B. Haessler, J. Giulianini, F. Bradford, Y. Miller, J.E. Campbell, A. Lin, K. Millwood, I.Y. Rasheed, A. Hindy, G. Faul, J.D. Zhao, W. Weir, D.R. Turman, C. Huang, H. Graff, M. Choudhury, A. Sengupta, D. Mahajan, A. Brown, M.R. Zhang, W. Yu, K. Schmidt, E.M. Pandit, A. Gustafsson, S. Yin, X. Luan, J. Zhao, J.-H. Matsuda, F. Jang, H.-M. Yoon, K. Medina-Gomez, C. Pitsillides, A. Hottenga, J.J. Wood, A.R. Ji, Y. Gao, Z. Haworth, S. Mitchell, R.E. Chai, J.F. Aadahl, M. Bjerregaard, A.A. Yao, J. Manichaikul, A. Lee, W.-J. Hsiung, C.A. Warren, H.R. Ramirez, J. Bork-Jensen, J. Kårhus, L.L. Goel, A. Sabater-Lleal, M. Noordam, R. Mauro, P. Matteo, F. McDaid, A.F. Marques-Vidal, P. Wielscher, M. Trompet, S. Sattar, N. Møllehave, L.T. Munz, M. Zeng, L. Huang, J. Yang, B. Poveda, A. Kurbasic, A. Schönherr, S. Forer, L. Scholz, M. Galesloot, T.E. Bradfield, J.P. Ruotsalainen, S.E. Daw, E.W. Zmuda, J.M. Mitchell, J.S. Fuchsberger, C. Christensen, H. Brody, J.A. Le, P. Feitosa, M.F. Wojczynski, M.K. Hemerich, D. Preuss, M. Mangino, M. Christofidou, P. Verweij, N. Benjamins, J.W. Engmann, J. Noah, T.L. Verma, A. Slieker, R.C. Lo, K.S. Zilhao, N.R. Kleber, M.E. Delgado, G.E. Huo, S. Ikeda, D.D. Iha, H. Yang, J. Liu, J. Demirkan, A. Leonard, H.L. Marten, J. Emmel, C. Schmidt, B. Smyth, L.J. Cañadas-Garre, M. Wang, C. Nakatochi, M. Wong, A. Hutri-Kähönen, N. Sim, X. Xia, R. Huerta-Chagoya, A. Fernandez-Lopez, J.C. Ly
- Abstract
A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology. © 2022 American Society of Human Genetics
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- 2022
29. A saturated map of common genetic variants associated with human height
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Yengo, L. Vedantam, S. Marouli, E. Sidorenko, J. Bartell, E. Sakaue, S. Graff, M. Eliasen, A.U. Jiang, Y. Raghavan, S. Miao, J. Arias, J.D. Graham, S.E. Mukamel, R.E. Spracklen, C.N. Yin, X. Chen, S.-H. Ferreira, T. Highland, H.H. Ji, Y. Karaderi, T. Lin, K. Lüll, K. Malden, D.E. Medina-Gomez, C. Machado, M. Moore, A. Rüeger, S. Sim, X. Vrieze, S. Ahluwalia, T.S. Akiyama, M. Allison, M.A. Alvarez, M. Andersen, M.K. Ani, A. Appadurai, V. Arbeeva, L. Bhaskar, S. Bielak, L.F. Bollepalli, S. Bonnycastle, L.L. Bork-Jensen, J. Bradfield, J.P. Bradford, Y. Braund, P.S. Brody, J.A. Burgdorf, K.S. Cade, B.E. Cai, H. Cai, Q. Campbell, A. Cañadas-Garre, M. Catamo, E. Chai, J.-F. Chai, X. Chang, L.-C. Chang, Y.-C. Chen, C.-H. Chesi, A. Choi, S.H. Chung, R.-H. Cocca, M. Concas, M.P. Couture, C. Cuellar-Partida, G. Danning, R. Daw, E.W. Degenhard, F. Delgado, G.E. Delitala, A. Demirkan, A. Deng, X. Devineni, P. Dietl, A. Dimitriou, M. Dimitrov, L. Dorajoo, R. Ekici, A.B. Engmann, J.E. Fairhurst-Hunter, Z. Farmaki, A.-E. Faul, J.D. Fernandez-Lopez, J.-C. Forer, L. Francescatto, M. Freitag-Wolf, S. Fuchsberger, C. Galesloot, T.E. Gao, Y. Gao, Z. Geller, F. Giannakopoulou, O. Giulianini, F. Gjesing, A.P. Goel, A. Gordon, S.D. Gorski, M. Grove, J. Guo, X. Gustafsson, S. Haessler, J. Hansen, T.F. Havulinna, A.S. Haworth, S.J. He, J. Heard-Costa, N. Hebbar, P. Hindy, G. Ho, Y.-L.A. Hofer, E. Holliday, E. Horn, K. Hornsby, W.E. Hottenga, J.-J. Huang, H. Huang, J. Huerta-Chagoya, A. Huffman, J.E. Hung, Y.-J. Huo, S. Hwang, M.Y. Iha, H. Ikeda, D.D. Isono, M. Jackson, A.U. Jäger, S. Jansen, I.E. Johansson, I. Jonas, J.B. Jonsson, A. Jørgensen, T. Kalafati, I.-P. Kanai, M. Kanoni, S. Kårhus, L.L. Kasturiratne, A. Katsuya, T. Kawaguchi, T. Kember, R.L. Kentistou, K.A. Kim, H.-N. Kim, Y.J. Kleber, M.E. Knol, M.J. Kurbasic, A. Lauzon, M. Le, P. Lea, R. Lee, J.-Y. Leonard, H.L. Li, S.A. Li, X. Li, X. Liang, J. Lin, H. Lin, S.-Y. Liu, J. Liu, X. Lo, K.S. Long, J. Lores-Motta, L. Luan, J. Lyssenk and Yengo, L. Vedantam, S. Marouli, E. Sidorenko, J. Bartell, E. Sakaue, S. Graff, M. Eliasen, A.U. Jiang, Y. Raghavan, S. Miao, J. Arias, J.D. Graham, S.E. Mukamel, R.E. Spracklen, C.N. Yin, X. Chen, S.-H. Ferreira, T. Highland, H.H. Ji, Y. Karaderi, T. Lin, K. Lüll, K. Malden, D.E. Medina-Gomez, C. Machado, M. Moore, A. Rüeger, S. Sim, X. Vrieze, S. Ahluwalia, T.S. Akiyama, M. Allison, M.A. Alvarez, M. Andersen, M.K. Ani, A. Appadurai, V. Arbeeva, L. Bhaskar, S. Bielak, L.F. Bollepalli, S. Bonnycastle, L.L. Bork-Jensen, J. Bradfield, J.P. Bradford, Y. Braund, P.S. Brody, J.A. Burgdorf, K.S. Cade, B.E. Cai, H. Cai, Q. Campbell, A. Cañadas-Garre, M. Catamo, E. Chai, J.-F. Chai, X. Chang, L.-C. Chang, Y.-C. Chen, C.-H. Chesi, A. Choi, S.H. Chung, R.-H. Cocca, M. Concas, M.P. Couture, C. Cuellar-Partida, G. Danning, R. Daw, E.W. Degenhard, F. Delgado, G.E. Delitala, A. Demirkan, A. Deng, X. Devineni, P. Dietl, A. Dimitriou, M. Dimitrov, L. Dorajoo, R. Ekici, A.B. Engmann, J.E. Fairhurst-Hunter, Z. Farmaki, A.-E. Faul, J.D. Fernandez-Lopez, J.-C. Forer, L. Francescatto, M. Freitag-Wolf, S. Fuchsberger, C. Galesloot, T.E. Gao, Y. Gao, Z. Geller, F. Giannakopoulou, O. Giulianini, F. Gjesing, A.P. Goel, A. Gordon, S.D. Gorski, M. Grove, J. Guo, X. Gustafsson, S. Haessler, J. Hansen, T.F. Havulinna, A.S. Haworth, S.J. He, J. Heard-Costa, N. Hebbar, P. Hindy, G. Ho, Y.-L.A. Hofer, E. Holliday, E. Horn, K. Hornsby, W.E. Hottenga, J.-J. Huang, H. Huang, J. Huerta-Chagoya, A. Huffman, J.E. Hung, Y.-J. Huo, S. Hwang, M.Y. Iha, H. Ikeda, D.D. Isono, M. Jackson, A.U. Jäger, S. Jansen, I.E. Johansson, I. Jonas, J.B. Jonsson, A. Jørgensen, T. Kalafati, I.-P. Kanai, M. Kanoni, S. Kårhus, L.L. Kasturiratne, A. Katsuya, T. Kawaguchi, T. Kember, R.L. Kentistou, K.A. Kim, H.-N. Kim, Y.J. Kleber, M.E. Knol, M.J. Kurbasic, A. Lauzon, M. Le, P. Lea, R. Lee, J.-Y. Leonard, H.L. Li, S.A. Li, X. Li, X. Liang, J. Lin, H. Lin, S.-Y. Liu, J. Liu, X. Lo, K.S. Long, J. Lores-Motta, L. Luan, J. Lyssenk
- Abstract
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries. © 2022, The Author(s).
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- 2022
30. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
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Kanoni, S. Graham, S.E. Wang, Y. Surakka, I. Ramdas, S. Zhu, X. Clarke, S.L. Bhatti, K.F. Vedantam, S. Winkler, T.W. Locke, A.E. Marouli, E. Zajac, G.J.M. Wu, K.-H.H. Ntalla, I. Hui, Q. Klarin, D. Hilliard, A.T. Wang, Z. Xue, C. Thorleifsson, G. Helgadottir, A. Gudbjartsson, D.F. Holm, H. Olafsson, I. Hwang, M.Y. Han, S. Akiyama, M. Sakaue, S. Terao, C. Kanai, M. Zhou, W. Brumpton, B.M. Rasheed, H. Havulinna, A.S. Veturi, Y. Pacheco, J.A. Rosenthal, E.A. Lingren, T. Feng, Q.P. Kullo, I.J. Narita, A. Takayama, J. Martin, H.C. Hunt, K.A. Trivedi, B. Haessler, J. Giulianini, F. Bradford, Y. Miller, J.E. Campbell, A. Lin, K. Millwood, I.Y. Rasheed, A. Hindy, G. Faul, J.D. Zhao, W. Weir, D.R. Turman, C. Huang, H. Graff, M. Choudhury, A. Sengupta, D. Mahajan, A. Brown, M.R. Zhang, W. Yu, K. Schmidt, E.M. Pandit, A. Gustafsson, S. Yin, X. Luan, J. Zhao, J.-H. Matsuda, F. Jang, H.-M. Yoon, K. Medina-Gomez, C. Pitsillides, A. Hottenga, J.J. Wood, A.R. Ji, Y. Gao, Z. Haworth, S. Yousri, N.A. Mitchell, R.E. Chai, J.F. Aadahl, M. Bjerregaard, A.A. Yao, J. Manichaikul, A. Hwu, C.-M. Hung, Y.-J. Warren, H.R. Ramirez, J. Bork-Jensen, J. Kårhus, L.L. Goel, A. Sabater-Lleal, M. Noordam, R. Mauro, P. Matteo, F. McDaid, A.F. Marques-Vidal, P. Wielscher, M. Trompet, S. Sattar, N. Møllehave, L.T. Munz, M. Zeng, L. Huang, J. Yang, B. Poveda, A. Kurbasic, A. Lamina, C. Forer, L. Scholz, M. Galesloot, T.E. Bradfield, J.P. Ruotsalainen, S.E. Daw, E.W. Zmuda, J.M. Mitchell, J.S. Fuchsberger, C. Christensen, H. Brody, J.A. Vazquez-Moreno, M. Feitosa, M.F. Wojczynski, M.K. Wang, Z. Preuss, M.H. Mangino, M. Christofidou, P. Verweij, N. Benjamins, J.W. Engmann, J. Tsao, N.L. Verma, A. Slieker, R.C. Lo, K.S. Zilhao, N.R. Le, P. Kleber, M.E. Delgado, G.E. Huo, S. Ikeda, D.D. Iha, H. Yang, J. Liu, J. Demirkan, A. Leonard, H.L. Marten, J. Frank, M. Schmidt, B. Smyth, L.J. Cañadas-Garre, M. Wang, C. Nakatochi, M. Wong, A. Hutri-Kähönen, N. Sim, X. Xia, R. Huerta-Chagoya, A. Fernandez-Lopez, J.C. Lyss and Kanoni, S. Graham, S.E. Wang, Y. Surakka, I. Ramdas, S. Zhu, X. Clarke, S.L. Bhatti, K.F. Vedantam, S. Winkler, T.W. Locke, A.E. Marouli, E. Zajac, G.J.M. Wu, K.-H.H. Ntalla, I. Hui, Q. Klarin, D. Hilliard, A.T. Wang, Z. Xue, C. Thorleifsson, G. Helgadottir, A. Gudbjartsson, D.F. Holm, H. Olafsson, I. Hwang, M.Y. Han, S. Akiyama, M. Sakaue, S. Terao, C. Kanai, M. Zhou, W. Brumpton, B.M. Rasheed, H. Havulinna, A.S. Veturi, Y. Pacheco, J.A. Rosenthal, E.A. Lingren, T. Feng, Q.P. Kullo, I.J. Narita, A. Takayama, J. Martin, H.C. Hunt, K.A. Trivedi, B. Haessler, J. Giulianini, F. Bradford, Y. Miller, J.E. Campbell, A. Lin, K. Millwood, I.Y. Rasheed, A. Hindy, G. Faul, J.D. Zhao, W. Weir, D.R. Turman, C. Huang, H. Graff, M. Choudhury, A. Sengupta, D. Mahajan, A. Brown, M.R. Zhang, W. Yu, K. Schmidt, E.M. Pandit, A. Gustafsson, S. Yin, X. Luan, J. Zhao, J.-H. Matsuda, F. Jang, H.-M. Yoon, K. Medina-Gomez, C. Pitsillides, A. Hottenga, J.J. Wood, A.R. Ji, Y. Gao, Z. Haworth, S. Yousri, N.A. Mitchell, R.E. Chai, J.F. Aadahl, M. Bjerregaard, A.A. Yao, J. Manichaikul, A. Hwu, C.-M. Hung, Y.-J. Warren, H.R. Ramirez, J. Bork-Jensen, J. Kårhus, L.L. Goel, A. Sabater-Lleal, M. Noordam, R. Mauro, P. Matteo, F. McDaid, A.F. Marques-Vidal, P. Wielscher, M. Trompet, S. Sattar, N. Møllehave, L.T. Munz, M. Zeng, L. Huang, J. Yang, B. Poveda, A. Kurbasic, A. Lamina, C. Forer, L. Scholz, M. Galesloot, T.E. Bradfield, J.P. Ruotsalainen, S.E. Daw, E.W. Zmuda, J.M. Mitchell, J.S. Fuchsberger, C. Christensen, H. Brody, J.A. Vazquez-Moreno, M. Feitosa, M.F. Wojczynski, M.K. Wang, Z. Preuss, M.H. Mangino, M. Christofidou, P. Verweij, N. Benjamins, J.W. Engmann, J. Tsao, N.L. Verma, A. Slieker, R.C. Lo, K.S. Zilhao, N.R. Le, P. Kleber, M.E. Delgado, G.E. Huo, S. Ikeda, D.D. Iha, H. Yang, J. Liu, J. Demirkan, A. Leonard, H.L. Marten, J. Frank, M. Schmidt, B. Smyth, L.J. Cañadas-Garre, M. Wang, C. Nakatochi, M. Wong, A. Hutri-Kähönen, N. Sim, X. Xia, R. Huerta-Chagoya, A. Fernandez-Lopez, J.C. Lyss
- Abstract
Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk. © 2022, The Author(s).
- Published
- 2022
31. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
- Author
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Kanoni, S., Graham, S.E., Wang, Yuxuan, Surakka, I., Ramdas, S., Zhu, X, Clarke, S.L., Bhatti, K.F., Vedantam, S., Winkler, T.W., Locke, A.E., Marouli, E., Zajac, G.J.M., Wu, K.H., Ntalla, I., Hui, Q., Klarin, D., Hilliard, A.T., Wang, Zeyuan, Xue, C., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Hwang, M.Y., Han, S., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W, Brumpton, B.M., Rasheed, H., Havulinna, A.S., Veturi, Y., Pacheco, J.A., Rosenthal, E.A., Lingren, T., Feng, Q., Kullo, I.J., Narita, A., Takayama, J., Martin, H.C., Hunt, K.A., Trivedi, B., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Rasheed, A., Hindy, G., Faul, J.D., Zhao, Wei, Weir, D.R., Turman, C., Huang, H., Graff, M, Choudhury, A., Sengupta, D., Mahajan, A., Brown, M.R., Zhang, W, Yu, K., Schmidt, E.M., Pandit, A., Gustafsson, S., Yin, X., Luan, J, Zhao, J.H., Matsuda, F., Jang, H.M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J.J., Wood, A.R., Ji, Y., Gao, Z, Haworth, S., Yousri, N.A., Mitchell, R.E., Chai, J.F., Aadahl, M., Bjerregaard, A.A., Yao, J., Manichaikul, A., Hwu, C.M., Hung, Y.J., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Sabater-Lleal, M., Noordam, R., Mauro, P., Galesloot, T.E., Lores-Motta, L., Pauper, M., Hollander, A.I. den, Kiemeney, L.A.L.M., Graaf, J. de, Assimes, T.L., Peloso, G.M., Kanoni, S., Graham, S.E., Wang, Yuxuan, Surakka, I., Ramdas, S., Zhu, X, Clarke, S.L., Bhatti, K.F., Vedantam, S., Winkler, T.W., Locke, A.E., Marouli, E., Zajac, G.J.M., Wu, K.H., Ntalla, I., Hui, Q., Klarin, D., Hilliard, A.T., Wang, Zeyuan, Xue, C., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Hwang, M.Y., Han, S., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W, Brumpton, B.M., Rasheed, H., Havulinna, A.S., Veturi, Y., Pacheco, J.A., Rosenthal, E.A., Lingren, T., Feng, Q., Kullo, I.J., Narita, A., Takayama, J., Martin, H.C., Hunt, K.A., Trivedi, B., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Rasheed, A., Hindy, G., Faul, J.D., Zhao, Wei, Weir, D.R., Turman, C., Huang, H., Graff, M, Choudhury, A., Sengupta, D., Mahajan, A., Brown, M.R., Zhang, W, Yu, K., Schmidt, E.M., Pandit, A., Gustafsson, S., Yin, X., Luan, J, Zhao, J.H., Matsuda, F., Jang, H.M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J.J., Wood, A.R., Ji, Y., Gao, Z, Haworth, S., Yousri, N.A., Mitchell, R.E., Chai, J.F., Aadahl, M., Bjerregaard, A.A., Yao, J., Manichaikul, A., Hwu, C.M., Hung, Y.J., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Sabater-Lleal, M., Noordam, R., Mauro, P., Galesloot, T.E., Lores-Motta, L., Pauper, M., Hollander, A.I. den, Kiemeney, L.A.L.M., Graaf, J. de, Assimes, T.L., and Peloso, G.M.
- Abstract
Item does not contain fulltext, BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
- Published
- 2022
32. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- Author
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Ramdas, S., Judd, J., Graham, S.E., Kanoni, S., Wang, Y, Surakka, I., Wenz, B., Clarke, S.L., Chesi, A., Wells, A., Bhatti, K.F., Vedantam, S., Locke, A.E., Marouli, E., Zajac, G.J.M., Wu, K.H., Ntalla, I., Hui, Q., Klarin, D., Hilliard, A.T., Wang, Z, Xue, C., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Hwang, M.Y., Han, S., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W, Brumpton, B.M., Rasheed, H., Havulinna, A.S., Veturi, Y., Pacheco, J.A., Rosenthal, E.A., Lingren, T., Feng, Q., Kullo, I.J., Narita, A., Takayama, J., Martin, H.C., Hunt, K.A., Trivedi, B., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Rasheed, A., Hindy, G., Faul, J.D., Zhao, W, Weir, D.R., Turman, C., Huang, H., Graff, Mariaelisa, Choudhury, A., Sengupta, D., Mahajan, A., Brown, M.R., Yu, K., Schmidt, E.M., Pandit, A., Gustafsson, S., Yin, X., Luan, J, Zhao, J.H., Matsuda, F., Jang, H.M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J.J., Wood, A.R., Ji, Y., Gao, Z, Haworth, S., Mitchell, R.E., Chai, J.F., Aadahl, M., Bjerregaard, A.A., Yao, J., Manichaikul, A., Lee, W.J., Hsiung, C.A., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Galesloot, T.E., Lores de Motta, L., Pauper, M., Hollander, A.I. den, Kiemeney, L.A.L.M., Zhu, Xiang, Brown, C.D., Ramdas, S., Judd, J., Graham, S.E., Kanoni, S., Wang, Y, Surakka, I., Wenz, B., Clarke, S.L., Chesi, A., Wells, A., Bhatti, K.F., Vedantam, S., Locke, A.E., Marouli, E., Zajac, G.J.M., Wu, K.H., Ntalla, I., Hui, Q., Klarin, D., Hilliard, A.T., Wang, Z, Xue, C., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Hwang, M.Y., Han, S., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W, Brumpton, B.M., Rasheed, H., Havulinna, A.S., Veturi, Y., Pacheco, J.A., Rosenthal, E.A., Lingren, T., Feng, Q., Kullo, I.J., Narita, A., Takayama, J., Martin, H.C., Hunt, K.A., Trivedi, B., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Rasheed, A., Hindy, G., Faul, J.D., Zhao, W, Weir, D.R., Turman, C., Huang, H., Graff, Mariaelisa, Choudhury, A., Sengupta, D., Mahajan, A., Brown, M.R., Yu, K., Schmidt, E.M., Pandit, A., Gustafsson, S., Yin, X., Luan, J, Zhao, J.H., Matsuda, F., Jang, H.M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J.J., Wood, A.R., Ji, Y., Gao, Z, Haworth, S., Mitchell, R.E., Chai, J.F., Aadahl, M., Bjerregaard, A.A., Yao, J., Manichaikul, A., Lee, W.J., Hsiung, C.A., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Galesloot, T.E., Lores de Motta, L., Pauper, M., Hollander, A.I. den, Kiemeney, L.A.L.M., Zhu, Xiang, and Brown, C.D.
- Abstract
Item does not contain fulltext, A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
- Published
- 2022
33. Stroke genetics informs drug discovery and risk prediction across ancestries
- Author
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Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S
- Abstract
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
- Published
- 2022
34. A saturated map of common genetic variants associated with human height
- Author
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Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, 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SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN, Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, and Hirschhorn, JN
- Abstract
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
- Published
- 2022
35. Integrating bioenergy and food production—A case study of combined ethanol and dairy production in Pontal, Brazil
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Egeskog, A., Berndes, G., Freitas, F., Gustafsson, S., and Sparovek, G.
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- 2011
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36. On the control of HAB species using low biosurfactant concentrations
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Gustafsson, S., Hultberg, M., Figueroa, R.I., and Rengefors, K.
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- 2009
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37. Development of microstructure during creep of polycrystalline mullite and a nanocomposite mullite/5 vol.% SiC
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Gustafsson, S., Falk, L.K.L., Pitchford, J.E., Clegg, W.J., Lidén, E., and Carlström, E.
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- 2009
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38. A real-world analysis of characteristics and lipid-lowering therapy use in patients initiating treatment with evolocumab in Sweden
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Svensson, M K, primary, James, S, additional, Ravn-Fischer, A, additional, Pantev, E, additional, Sorio-Vilela, F, additional, Villa, G, additional, Cars, T, additional, Gustafsson, S, additional, and Hagstrom, E, additional
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- 2021
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- View/download PDF
39. An in vivo comparison of hip structure analysis (HSA) with measurements obtained by QCT
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Ramamurthi, K., Ahmad, O., Engelke, K., Taylor, R. H., Zhu, K., Gustafsson, S., Prince, R. L., and Wilson, K. E.
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- 2012
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40. Pressureless sintered Al 2O 3–SiC nanocomposites
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Gustafsson, S., Falk, L.K.L., Lidén, E., and Carlström, E.
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- 2008
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41. Poster session 3: Thursday 4 December 2014, 14: 00–18: 00Location: Poster area
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Lindqvist, G, Henein, MY, Backman, C, Gustafsson, S, and Morner, S
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- 2014
42. Comparison of QCT-derived and DXA-derived areal bone mineral density and T scores
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Khoo, B. C. C., Brown, K., Cann, C., Zhu, K., Henzell, S., Low, V., Gustafsson, S., Price, R. I., and Prince, R. L.
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- 2009
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43. TEM investigation of magnetite nanoparticles for biomedical applications
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Gustafsson, S., Fornara, A., Ye, F., Petersson, K., Johansson, C., Muhammed, M., Olsson, E., Richter, Silvia, editor, and Schwedt, Alexander, editor
- Published
- 2008
- Full Text
- View/download PDF
44. The power of genetic diversity in genome-wide association studies of lipids
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Graham, S.E., Clarke, S.L., Wu, K.H., Kanoni, S., Zajac, G.J.M., Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T.W., Locke, A.E., Marouli, E., Hwang, M.Y., Han, S., Narita, A., Choudhury, A., Bentley, A.R., Ekoru, K., Verma, A., Trivedi, B., Martin, H.C., Hunt, K.A., Hui, Q., Klarin, D., Zhu, X, Thorleifsson, G., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B.M., Rasheed, H., Ruotsalainen, S.E., Havulinna, A.S., Veturi, Y., Feng, Q., Rosenthal, E.A., Lingren, T., Pacheco, J.A., Pendergrass, S.A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Hindy, G., Rasheed, A., Faul, J.D., Zhao, W., Weir, D.R., Turman, C., Huang, H., Graff, M, Mahajan, A., Brown, M.R., Zhang, W., Yu, K., Schmidt, E.M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J.H., Matsuda, F., Jang, H.M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J.J., Willemsen, G., Wood, A.R., Ji, Y., Gao, Z, Haworth, S., Mitchell, R.E., Chai, J.F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., McDaid, A.F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Galesloot, T.E., Kiemeney, B., Graaf, J. de, Lores de Motta, L., Pauper, M., Hollander, A.I. den, Sun, Y.V., Willer, C.J., Graham, S.E., Clarke, S.L., Wu, K.H., Kanoni, S., Zajac, G.J.M., Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T.W., Locke, A.E., Marouli, E., Hwang, M.Y., Han, S., Narita, A., Choudhury, A., Bentley, A.R., Ekoru, K., Verma, A., Trivedi, B., Martin, H.C., Hunt, K.A., Hui, Q., Klarin, D., Zhu, X, Thorleifsson, G., Helgadottir, A., Gudbjartsson, D.F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B.M., Rasheed, H., Ruotsalainen, S.E., Havulinna, A.S., Veturi, Y., Feng, Q., Rosenthal, E.A., Lingren, T., Pacheco, J.A., Pendergrass, S.A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J.E., Campbell, A., Lin, K., Millwood, I.Y., Hindy, G., Rasheed, A., Faul, J.D., Zhao, W., Weir, D.R., Turman, C., Huang, H., Graff, M, Mahajan, A., Brown, M.R., Zhang, W., Yu, K., Schmidt, E.M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J.H., Matsuda, F., Jang, H.M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J.J., Willemsen, G., Wood, A.R., Ji, Y., Gao, Z, Haworth, S., Mitchell, R.E., Chai, J.F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H.R., Ramirez, J., Bork-Jensen, J., Kårhus, L.L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., McDaid, A.F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Galesloot, T.E., Kiemeney, B., Graaf, J. de, Lores de Motta, L., Pauper, M., Hollander, A.I. den, Sun, Y.V., and Willer, C.J.
- Abstract
Item does not contain fulltext, Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use(1). Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels(2), heart disease remains the leading cause of death worldwide(3). Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS(4-23) have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns(24). Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine(25), we anticipate that increased diversity of participants will lead to more accurate and equitable(26) application of polygenic scores in clinical practice.
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- 2021
45. The power of genetic diversity in genome-wide association studies of lipids
- Author
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Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), Willer, C. J. (Cristen J.), Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), and Willer, C. J. (Cristen J.)
- Abstract
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4‐23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.
- Published
- 2021
46. The trans-ancestral genomic architecture of glycemic traits
- Author
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Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), Barroso, I. (Ines), Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), and Barroso, I. (Ines)
- Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
- Published
- 2021
47. The trans-ancestral genomic architecture of glycemic traits
- Author
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Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), Tremoli E., Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), and Tremoli E.
- Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
- Published
- 2021
48. On the Use of the Transient Hot-Strip Method for Measuring the Thermal Conductivity of High-Conducting Thin Bars
- Author
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Gustavsson, M., Wang, H., Trejo, R. M., Lara-Curzio, E., Dinwiddie, R. B., and Gustafsson, S. E.
- Published
- 2006
- Full Text
- View/download PDF
49. Quality control and conduct of genome-wide association meta-analyses
- Author
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Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, 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WH, Palmer CN, Palmer LJ, Palotie A, Paré G, Parker AN, Paternoster L, Pawitan Y, Pechlivanis S, Peden JF, Pedersen NL, Pedersen O, Pellikka N, Peltonen L, Penninx B, Perola M, Perry JR, Person T, Peters A, Peters MJ, Pichler I, Pietiläinen KH, Platou CG, Polasek O, Pouta A, Power C, Pramstaller PP, Preuss M, Price JF, Prokopenko I, Province MA, Psaty BM, Purcell S, Pütter C, Qi L, Quertermous T, Radhakrishnan A, Raitakari O, Randall JC, Rauramaa R, Rayner NW, Rehnberg E, Rendon A, Ridderstråle M, Ridker PM, Ripatti S, Rissanen A, Rivadeneira F, Rivolta C, Robertson NR, Rose LM, Rudan I, Saaristo TE, Sager H, Salomaa V, Samani NJ, Sambrook JG, Sanders AR, Sandholt C, Sanna S, Saramies J, Schadt EE, Scherag A, Schipf S, Schlessinger D, Schreiber S, Schunkert H, Schwarz PE, Scott LJ, Shi J, Shin SY, Shuldiner AR, Shungin D, Signorini S, Silander K, Sinisalo J, Skrobek B, Smit JH, Smith AV, Smith GD, Snieder H, Soranzo N, Sørensen TI, Sovio U, Spector TD, Speliotes EK, Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, Zgaga L, Zhao JH, 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- Subjects
Quality Control ,Netherlands Twin Register (NTR) ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,media_common.quotation_subject ,quality control, GWAMAS ,Control (management) ,Medizin ,Genome-wide association study ,Biology ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Software ,SDG 17 - Partnerships for the Goals ,Meta-Analysis as Topic ,Comparable size ,Quality (business) ,030304 developmental biology ,media_common ,Protocol (science) ,0303 health sciences ,business.industry ,Software package ,Data science ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Genome-Wide Association Study/methods ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,quality control ,genome-wide association meta-analyses ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Item does not contain fulltext Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
- Published
- 2014
- Full Text
- View/download PDF
50. Genetic diversity in the rare orchid Gymnadenia odoratissima and a comparison with the more common congener, G. conopsea
- Author
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Gustafsson, S. and Sjögren-Gulve, P.
- Published
- 2002
- Full Text
- View/download PDF
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