Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity (original) (raw)
- Article
- Published: 14 December 2008
- G Bragi Walters1 na1,
- Daniel F Gudbjartsson1,
- Valgerdur Steinthorsdottir1,
- Patrick Sulem1,
- Anna Helgadottir1,
- Unnur Styrkarsdottir1,
- Solveig Gretarsdottir1,
- Steinunn Thorlacius1,
- Ingileif Jonsdottir1,2,
- Thorbjorg Jonsdottir1,
- Elinborg J Olafsdottir3,
- Gudridur H Olafsdottir3,
- Thorvaldur Jonsson2,4,
- Frosti Jonsson1,
- Knut Borch-Johnsen5,6,
- Torben Hansen5,
- Gitte Andersen5,
- Torben Jorgensen7,8,
- Torsten Lauritzen9,
- Katja K Aben10,
- André LM Verbeek11,
- Nel Roeleveld11,
- Ellen Kampman11,
- Lisa R Yanek12,
- Lewis C Becker12,
- Laufey Tryggvadottir3,
- Thorunn Rafnar1,
- Diane M Becker12,
- Jeffrey Gulcher1,
- Lambertus A Kiemeney10,11,13,
- Oluf Pedersen5,6,8,
- Augustine Kong1,
- Unnur Thorsteinsdottir1,2 &
- …
- Kari Stefansson1,2
Nature Genetics volume 41, pages 18–24 (2009)Cite this article
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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
- Gudmar Thorleifsson and G Bragi Walters: These authors contributed equally to this work.
Authors and Affiliations
- 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 - Faculty of Medicine, University of Iceland, Reykjavík, 101, Iceland
Ingileif Jonsdottir, Thorvaldur Jonsson, Unnur Thorsteinsdottir & Kari Stefansson - Icelandic Cancer Registry, Reykjavik, 105, Iceland
Elinborg J Olafsdottir, Gudridur H Olafsdottir & Laufey Tryggvadottir - Department of Surgery, University Hospital, Reykjavik, 101, Iceland
Thorvaldur Jonsson - Steno Diabetes Center, Copenhagen, DK-2820, Denmark
Knut Borch-Johnsen, Torben Hansen, Gitte Andersen & Oluf Pedersen - Faculty of Health Science, University of Aarhus, Aarhus, DK-8000, Denmark
Knut Borch-Johnsen & Oluf Pedersen - Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, DK-2600, Denmark
Torben Jorgensen - Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
Torben Jorgensen & Oluf Pedersen - The Department of General Medical Practice, University of Aarhus, Aarhus, DK-8000, Denmark
Torsten Lauritzen - Comprehensive Cancer Centre East, Nijmegen, 6500 HB, The Netherlands
Katja K Aben & Lambertus A Kiemeney - Radboud University Nijmegen Medical Center Department of Epidemiology & Biostatistics, Nijmegen, 6500 HB, The Netherlands
André LM Verbeek, Nel Roeleveld, Ellen Kampman & Lambertus A Kiemeney - 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 - Radboud University Nijmegen Department of Urology, Nijmegen, 6500 HB, The Netherlands
Lambertus A Kiemeney
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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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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
- Received: 07 July 2008
- Accepted: 08 October 2008
- Published: 14 December 2008
- Issue Date: January 2009
- DOI: https://doi.org/10.1038/ng.274