Genome-wide association study of copy number variation identified gremlin1 as a candidate gene for lean body mass

J Hum Genet. 2012 Jan;57(1):33-7. doi: 10.1038/jhg.2011.125. Epub 2011 Nov 3.

Abstract

Lean body mass (LBM) is a heritable trait predicting a series of health problems, such as osteoporotic fracture and sarcopenia. We aim to identify sequence variants associated with LBM by a genome-wide association study (GWAS) of copy number variants (CNVs). We genotyped genome-wide CNVs of 1627 individuals of the Chinese population with Affymetrix SNP6.0 genotyping platform, which comprised of 9 40 000 copy number probes. We then performed a GWAS of CNVs with lean mass at seven sites: left and right arms, left and right legs, total of limb, trunk and whole body. We identified a CNV that is associated with LBM variation at the genome-wide significance level (CNV2073, Bonferroni corrected P-value 0.002 at right arm). CNV2073 locates at chromosome 15q13.3, which has been implicated as a candidate region for LBM by our previous linkage studies. The nearest gene, gremlin1, has a key role in the regulation of skeletal muscle formation and repair. Our results suggest that the gremlin1 gene is a potentially important gene for LBM variation. Our findings also show the utility and efficacy of CNV as genetic markers in association studies.

Publication types

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

MeSH terms

  • Adult
  • Body Weight / genetics*
  • DNA Copy Number Variations / genetics*
  • Female
  • Genetic Association Studies*
  • Genome-Wide Association Study*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Thinness / genetics*

Substances

  • GREM1 protein, human
  • Intercellular Signaling Peptides and Proteins