Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Hum Mol Genet. 2014 Oct 15;23(20):5492-504. doi: 10.1093/hmg/ddu248. Epub 2014 May 26.

Abstract

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / genetics*
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Asian Continental Ancestry Group / genetics*
  • Blood Proteins / genetics*
  • Body Mass Index
  • Cardiac Myosins / genetics*
  • Far East
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glycoproteins / genetics*
  • Humans
  • KCNQ1 Potassium Channel / genetics*
  • Male
  • Myosin Light Chains / genetics*
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Proteinase Inhibitory Proteins, Secretory / genetics*

Substances

  • Blood Proteins
  • Glycoproteins
  • ITIH4 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Myosin Light Chains
  • Proteinase Inhibitory Proteins, Secretory
  • myosin light chain 2
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial
  • 5'-Nucleotidase
  • NT5C2 protein, human
  • Cardiac Myosins

Grant support