Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity (original) (raw)

Nature Genetics volume 41, pages 18–24 (2009)Cite this article

Abstract

Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 × 10−7. This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.

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Acknowledgements

The authors would like to thank all of the study participants and clinical collaborators for their cooperation. We would also like to acknowledge the staff at the Clinical Research Centre (Iceland) and the deCODE Genetics biological materials and genotyping facilities for their work. The research performed at deCODE Genetics was part funded through the European Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413. deCODE Genetics would like to thank the GIANT Consortium for their cooperation and in particular J.N. Hirschhorn, M.I. McCarthy, C.M. Lindgren, J.C. Randall and S. Li for providing genome wide association results for the BMI and weight analysis. The US data collection was supported by grants HL072518 and HL087698 from the National Institutes of Health, the Johns Hopkins General Clinical Research Center, the National Center for Research Resources (M01-RR000052), and the National Institutes of Health. The Danish study was supported by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP) and the Danish Health Research Council.

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Author notes

  1. Gudmar Thorleifsson and G Bragi Walters: These authors contributed equally to this work.

Authors and Affiliations

  1. deCODE Genetics, Reykjavik, 101, Iceland
    Gudmar Thorleifsson, G Bragi Walters, Daniel F Gudbjartsson, Valgerdur Steinthorsdottir, Patrick Sulem, Anna Helgadottir, Unnur Styrkarsdottir, Solveig Gretarsdottir, Steinunn Thorlacius, Ingileif Jonsdottir, Thorbjorg Jonsdottir, Frosti Jonsson, Thorunn Rafnar, Jeffrey Gulcher, Augustine Kong, Unnur Thorsteinsdottir & Kari Stefansson
  2. Faculty of Medicine, University of Iceland, Reykjavík, 101, Iceland
    Ingileif Jonsdottir, Thorvaldur Jonsson, Unnur Thorsteinsdottir & Kari Stefansson
  3. Icelandic Cancer Registry, Reykjavik, 105, Iceland
    Elinborg J Olafsdottir, Gudridur H Olafsdottir & Laufey Tryggvadottir
  4. Department of Surgery, University Hospital, Reykjavik, 101, Iceland
    Thorvaldur Jonsson
  5. Steno Diabetes Center, Copenhagen, DK-2820, Denmark
    Knut Borch-Johnsen, Torben Hansen, Gitte Andersen & Oluf Pedersen
  6. Faculty of Health Science, University of Aarhus, Aarhus, DK-8000, Denmark
    Knut Borch-Johnsen & Oluf Pedersen
  7. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, DK-2600, Denmark
    Torben Jorgensen
  8. Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
    Torben Jorgensen & Oluf Pedersen
  9. The Department of General Medical Practice, University of Aarhus, Aarhus, DK-8000, Denmark
    Torsten Lauritzen
  10. Comprehensive Cancer Centre East, Nijmegen, 6500 HB, The Netherlands
    Katja K Aben & Lambertus A Kiemeney
  11. Radboud University Nijmegen Medical Center Department of Epidemiology & Biostatistics, Nijmegen, 6500 HB, The Netherlands
    André LM Verbeek, Nel Roeleveld, Ellen Kampman & Lambertus A Kiemeney
  12. The Johns Hopkins Sibling and Family Heart Study, The Johns Hopkins University School of Medicine, Baltimore, 21287, Maryland, USA
    Lisa R Yanek, Lewis C Becker & Diane M Becker
  13. Radboud University Nijmegen Department of Urology, Nijmegen, 6500 HB, The Netherlands
    Lambertus A Kiemeney

Authors

  1. Gudmar Thorleifsson
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  2. G Bragi Walters
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  3. Daniel F Gudbjartsson
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  4. Valgerdur Steinthorsdottir
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  5. Patrick Sulem
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  6. Anna Helgadottir
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  7. Unnur Styrkarsdottir
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  8. Solveig Gretarsdottir
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  9. Steinunn Thorlacius
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  10. Ingileif Jonsdottir
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  11. Thorbjorg Jonsdottir
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  12. Elinborg J Olafsdottir
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  13. Gudridur H Olafsdottir
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  14. Thorvaldur Jonsson
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  15. Frosti Jonsson
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  16. Knut Borch-Johnsen
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  17. Torben Hansen
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  18. Gitte Andersen
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  19. Torben Jorgensen
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  20. Torsten Lauritzen
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  21. Katja K Aben
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  22. André LM Verbeek
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  23. Nel Roeleveld
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  24. Ellen Kampman
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  25. Lisa R Yanek
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  26. Lewis C Becker
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  27. Laufey Tryggvadottir
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  28. Thorunn Rafnar
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  29. Diane M Becker
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  30. Jeffrey Gulcher
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  31. Lambertus A Kiemeney
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  32. Oluf Pedersen
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  33. Augustine Kong
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  34. Unnur Thorsteinsdottir
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  35. Kari Stefansson
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Contributions

G.T., G.B.W., U.T. and K.S. wrote the first draft of the paper. G.B.W., V.S., A.H., U.S., S.G., S.T., I.J., E.J.O., G.H.O., T. Jonsson, L.T. and T.R. participated in the collection of the Icelandic data. K.B.-J., T.H., G.A., T. Jorgensen, T.L. and O.P. recruited and phenotyped the Danish study samples. K.K.A., A.L.M.V., N.R., E.K. and L.A.K. collected the Dutch data. D.M.B., L.R.Y. and L.C.B. collected the US data. G.T., G.B.W., D.F.G. and P.S. analyzed the data. G.B.W., T. Jonsdottir and F.J. carried out the genotyping. G.T., G.B.W., J.G., A.K., U.T. and K.S. planned and supervised the work. All authors contributed to the final version of the paper.

Corresponding authors

Correspondence toGudmar Thorleifsson or Kari Stefansson.

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Some of the authors are employed by deCODE Genetics and own stock or stock options in the company.

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Thorleifsson, G., Walters, G., Gudbjartsson, D. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.Nat Genet 41, 18–24 (2009). https://doi.org/10.1038/ng.274

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