Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Original publication

DOI

10.1038/ng.686

Type

Journal article

Journal

Nature genetics

Publication Date

11/2010

Volume

42

Pages

937 - 948

Addresses

Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.

Keywords

MAGIC, Procardis Consortium, Humans, Obesity, Genetic Predisposition to Disease, Body Weight, Body Mass Index, Body Size, Body Height, Chromosome Mapping, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Genome-Wide Association Study