Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

To investigate the genetic architecture of severe obesity, we performed a genome-wide association study of 775 cases and 3197 unascertained controls at approximately 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.

Original publication

DOI

10.1093/hmg/ddp292

Type

Journal article

Journal

Human molecular genetics

Publication Date

09/2009

Volume

18

Pages

3502 - 3507

Addresses

Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.

Keywords

GIANT Consortium, Humans, Obesity, Genetic Markers, Body Mass Index, Risk Factors, Cohort Studies, Phenotype, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Middle Aged, Female, Male