Implication of European-derived Adiposity Loci in African Americans

Int J Obes (Lond). 2012 Mar;36(3):465-73. doi: 10.1038/ijo.2011.131. Epub 2011 Jul 12.

Abstract

Objective: Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans.

Methods: A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results.

Results: Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005<P<0.05, and had effect sizes between 0.04 and 0.06 s.d. units (or 0.30 to 0.44 g m(-2)) of BMI for each copy of the BMI-increasing allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P=0.005, 0.020 and 0.019, respectively).

Conclusion: We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adiposity / genetics
  • African Americans / genetics*
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Weight / genetics*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • European Continental Ancestry Group / genetics*
  • Female
  • GPI-Linked Proteins / genetics
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Obesity / epidemiology
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Proteins / genetics
  • Receptor, Melanocortin, Type 4 / genetics
  • Transcription Factors

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules, Neuronal
  • GPI-Linked Proteins
  • MC4R protein, human
  • Membrane Proteins
  • NEGR1 protein, human
  • Proteins
  • Receptor, Melanocortin, Type 4
  • SH2B1 protein, human
  • TMEM18 protein, human
  • Transcription Factors
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human