Common body mass index-associated variants confer risk of extreme obesity (original) (raw)

Journal Article

Chris Cotsapas ,

1

Center for Human Genetic Research

and

2

Gastrointestinal Unit

,

Massachusetts General Hospital

,

Boston, MA

,

USA

,

3

Department of Medicine

,

Harvard Medical School

,

Boston, MA

,

USA

,

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Elizabeth K. Speliotes ,

3

Department of Medicine

,

Harvard Medical School

,

Boston, MA

,

USA

,

4

Medical and Population Genetics Program

and

5

Metabolism Initiative

,

Broad Institute of MIT and Harvard

,

Cambridge, MA

,

USA

,

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Ida J. Hatoum ,

5

Metabolism Initiative

,

Broad Institute of MIT and Harvard

,

Cambridge, MA

,

USA

,

6

MGH Weight Center

,

Massachusetts General Hospital and Harvard Medical School

,

Boston, MA

,

USA

,

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Danielle M. Greenawalt ,

7

Genetics Rosetta Inpharmatics LLC

,

a wholly owned subsidiary of Merck & Co., Inc.

,

Seattle, WA 98109

,

USA

,

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Radu Dobrin ,

7

Genetics Rosetta Inpharmatics LLC

,

a wholly owned subsidiary of Merck & Co., Inc.

,

Seattle, WA 98109

,

USA

,

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Pek Y. Lum ,

7

Genetics Rosetta Inpharmatics LLC

,

a wholly owned subsidiary of Merck & Co., Inc.

,

Seattle, WA 98109

,

USA

,

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Christine Suver ,

7

Genetics Rosetta Inpharmatics LLC

,

a wholly owned subsidiary of Merck & Co., Inc.

,

Seattle, WA 98109

,

USA

,

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Eugene Chudin ,

7

Genetics Rosetta Inpharmatics LLC

,

a wholly owned subsidiary of Merck & Co., Inc.

,

Seattle, WA 98109

,

USA

,

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Daniel Kemp ,

8

Department of Metabolic Disorders

,

Merck Research Laboratories

,

Rahway, NJ 07065

,

USA

and

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Marc Reitman ,

8

Department of Metabolic Disorders

,

Merck Research Laboratories

,

Rahway, NJ 07065

,

USA

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Received:

23 February 2009

Revision received:

10 June 2009

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Chris Cotsapas, Elizabeth K. Speliotes, Ida J. Hatoum, Danielle M. Greenawalt, Radu Dobrin, Pek Y. Lum, Christine Suver, Eugene Chudin, Daniel Kemp, Marc Reitman, Benjamin F. Voight, Benjamin M. Neale, Eric E. Schadt, Joel N. Hirschhorn, Lee M. Kaplan, Mark J. Daly, the GIANT Consortium, Common body mass index-associated variants confer risk of extreme obesity, Human Molecular Genetics, Volume 18, Issue 18, 15 September 2009, Pages 3502–3507, https://doi.org/10.1093/hmg/ddp292
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Abstract

To investigate the genetic architecture of severe obesity, we performed a genome-wide association study of 775 cases and 3197 unascertained controls at ∼550 000 markers across the autosomal genome. We found convincing association to the previously described locus including the FTO gene. We also found evidence of association at a further six of 12 other loci previously reported to influence body mass index (BMI) in the general population and one of three associations to severe childhood and adult obesity and that cases have a higher proportion of risk-conferring alleles than controls. We found no evidence of homozygosity at any locus due to identity-by-descent associating with phenotype which would be indicative of rare, penetrant alleles, nor was there excess genome-wide homozygosity in cases relative to controls. Our results suggest that variants influencing BMI also contribute to severe obesity, a condition at the extreme of the phenotypic spectrum rather than a distinct condition.

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Topic:

• alleles
• obesity
• phenotype
• body mass index procedure
• adult
• child
• genome
• homozygote
• obesity, morbid
• genetics
• genome-wide association study
• fto gene

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