Article abstract
Nature Genetics 41, 18 - 24 (2008)
Published online: 14 December 2008 | doi:10.1038/ng.274
Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity
Gudmar Thorleifsson1,14, G Bragi Walters1,14, 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
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.
- deCODE Genetics, 101 Reykjavik, Iceland.
- Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland.
- Icelandic Cancer Registry, 105 Reykjavik, Iceland.
- Department of Surgery, University Hospital, 101 Reykjavik, Iceland.
- Steno Diabetes Center, DK-2820 Copenhagen, Denmark.
- Faculty of Health Science, University of Aarhus, DK-8000 Aarhus, Denmark.
- Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
- Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
- The Department of General Medical Practice, University of Aarhus, DK-8000 Aarhus, Denmark.
- Comprehensive Cancer Centre East, 6500 HB Nijmegen, The Netherlands.
- Radboud University Nijmegen Medical Center Department of Epidemiology & Biostatistics, 6500 HB Nijmegen, The Netherlands.
- The Johns Hopkins Sibling and Family Heart Study, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
- Radboud University Nijmegen Department of Urology, 6500 HB Nijmegen, The Netherlands.
- These authors contributed equally to this work.
Correspondence to: Gudmar Thorleifsson1,14 e-mail: thorleif@decode.is
Correspondence to: Kari Stefansson1,2 e-mail: kstefans@decode.is
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