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

Gudmar Thorleifsson; G. Bragi Walters; Daniel F. Gudbjartsson; Valgerdur Steinthorsdottir; Patrick Sulem; Anna Helgadottir; Unnur Styrkarsdottir; Solveig Gretarsdottir; Steinunn Thorlacius; Ingileif Jonsdottir; Thorbjorg Jonsdottir; Elinborg J. Olafsdottir; Gudridur H. Olafsdottir; Thorvaldur Jonsson; Frosti Jonsson; Knut Borch-Johnsen; Torben Hansen; Gitte Andersen; Torben Jorgensen; Torsten Lauritzen; Katja K. Aben; André L.M. Verbeek; Nel Roeleveld; Ellen Kampman; Lisa R. Yanek; Lewis C. Becker; Laufey Tryggvadottir; Thorunn Rafnar; Diane M. Becker; Jeffrey Gulcher; Lambertus A. Kiemeney; Oluf Pedersen; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson

doi:10.1038/ng.274

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

Gudmar Thorleifsson^*
, G. Bragi Walters
, Daniel F. Gudbjartsson
, Valgerdur Steinthorsdottir
, Patrick Sulem
, Anna Helgadottir
, Unnur Styrkarsdottir
, Solveig Gretarsdottir
, Steinunn Thorlacius
, Ingileif Jonsdottir
, Thorbjorg Jonsdottir
, Elinborg J. Olafsdottir
, Gudridur H. Olafsdottir
, Thorvaldur Jonsson
, Frosti Jonsson
, Knut Borch-Johnsen
, Torben Hansen
, Gitte Andersen
, Torben Jorgensen
, Torsten Lauritzen

Katja K. Aben, André L.M. Verbeek, Nel Roeleveld, Ellen Kampman, Lisa R. Yanek, Lewis C. Becker, Laufey Tryggvadottir, Thorunn Rafnar, Diane M. Becker, Jeffrey Gulcher, Lambertus A. Kiemeney, Oluf Pedersen, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

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.

Original language	English
Pages (from-to)	18-24
Number of pages	7
Journal	Nature Genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1038/ng.274
Publication status	Published - 1 Jan 2009

Funding

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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Thorleifsson, G., Walters, G. B., Gudbjartsson, D. F., Steinthorsdottir, V., Sulem, P., Helgadottir, A., Styrkarsdottir, U., Gretarsdottir, S., Thorlacius, S., Jonsdottir, I., Jonsdottir, T., Olafsdottir, E. J., Olafsdottir, G. H., Jonsson, T., Jonsson, F., Borch-Johnsen, K., Hansen, T., Andersen, G., Jorgensen, T., ... Stefansson, K. (2009). Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nature Genetics, 41(1), 18-24. https://doi.org/10.1038/ng.274

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title = "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity",

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.",

author = "Gudmar Thorleifsson and Walters, \{G. Bragi\} and Gudbjartsson, \{Daniel F.\} and Valgerdur Steinthorsdottir and Patrick Sulem and Anna Helgadottir and Unnur Styrkarsdottir and Solveig Gretarsdottir and Steinunn Thorlacius and Ingileif Jonsdottir and Thorbjorg Jonsdottir and Olafsdottir, \{Elinborg J.\} and Olafsdottir, \{Gudridur H.\} and Thorvaldur Jonsson and Frosti Jonsson and Knut Borch-Johnsen and Torben Hansen and Gitte Andersen and Torben Jorgensen and Torsten Lauritzen and Aben, \{Katja K.\} and Verbeek, \{Andr{\'e} L.M.\} and Nel Roeleveld and Ellen Kampman and Yanek, \{Lisa R.\} and Becker, \{Lewis C.\} and Laufey Tryggvadottir and Thorunn Rafnar and Becker, \{Diane M.\} and Jeffrey Gulcher and Kiemeney, \{Lambertus A.\} and Oluf Pedersen and Augustine Kong and Unnur Thorsteinsdottir and Kari Stefansson",

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Thorleifsson, G, Walters, GB, Gudbjartsson, DF, Steinthorsdottir, V, Sulem, P, Helgadottir, A, Styrkarsdottir, U, Gretarsdottir, S, Thorlacius, S, Jonsdottir, I, Jonsdottir, T, Olafsdottir, EJ, Olafsdottir, GH, Jonsson, T, Jonsson, F, Borch-Johnsen, K, Hansen, T, Andersen, G, Jorgensen, T, Lauritzen, T, Aben, KK, Verbeek, ALM, Roeleveld, N, Kampman, E, Yanek, LR, Becker, LC, Tryggvadottir, L, Rafnar, T, Becker, DM, Gulcher, J, Kiemeney, LA, Pedersen, O, Kong, A, Thorsteinsdottir, U & Stefansson, K 2009, 'Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity', Nature Genetics, vol. 41, no. 1, pp. 18-24. https://doi.org/10.1038/ng.274

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AU - Thorleifsson, Gudmar

AU - Walters, G. Bragi

AU - Gudbjartsson, Daniel F.

AU - Steinthorsdottir, Valgerdur

AU - Sulem, Patrick

AU - Helgadottir, Anna

AU - Styrkarsdottir, Unnur

AU - Gretarsdottir, Solveig

AU - Thorlacius, Steinunn

AU - Jonsdottir, Ingileif

AU - Jonsdottir, Thorbjorg

AU - Olafsdottir, Elinborg J.

AU - Olafsdottir, Gudridur H.

AU - Jonsson, Thorvaldur

AU - Jonsson, Frosti

AU - Borch-Johnsen, Knut

AU - Hansen, Torben

AU - Andersen, Gitte

AU - Jorgensen, Torben

AU - Lauritzen, Torsten

AU - Aben, Katja K.

AU - Verbeek, André L.M.

AU - Roeleveld, Nel

AU - Kampman, Ellen

AU - Yanek, Lisa R.

AU - Becker, Lewis C.

AU - Tryggvadottir, Laufey

AU - Rafnar, Thorunn

AU - Becker, Diane M.

AU - Gulcher, Jeffrey

AU - Kiemeney, Lambertus A.

AU - Pedersen, Oluf

AU - Kong, Augustine

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

PY - 2009/1/1

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N2 - 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.

AB - 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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Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity

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