Identification of pleiotropic loci underlying hip bone mineral density and trunk lean mass

J Hum Genet. 2021 Mar;66(3):251-260. doi: 10.1038/s10038-020-00835-4. Epub 2020 Sep 14.

Abstract

Bone mineral density (BMD) and lean body mass (LBM) not only have a considerable heritability each, but also are genetically correlated. However, common genetic determinants shared by both traits are largely unknown. In the present study, we performed a bivariate genome-wide association study (GWAS) meta-analysis of hip BMD and trunk lean mass (TLM) in 11,335 subjects from 6 samples, and performed replication in estimated heel BMD and TLM in 215,234 UK Biobank (UKB) participants. We identified 2 loci that nearly attained the genome-wide significance (GWS, p < 5.0 × 10-8) level in the discovery GWAS meta-analysis and that were successfully replicated in the UKB sample: 11p15.2 (lead SNP rs12800228, discovery p = 2.88 × 10-7, replication p = 1.95 × 10-4) and 18q21.32 (rs489693, discovery p = 1.67 × 10-7, replication p = 1.17 × 10-3). The above 2 pleiotropic loci may play a pleiotropic role for hip BMD and TLM development. So our findings provide useful insights that further enhance our understanding of genetic interplay between BMD and LBM.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Body Composition / genetics*
  • Bone Density / genetics*
  • Cohort Studies
  • Ethnicity / genetics
  • Female
  • Femur / chemistry*
  • Genetic Heterogeneity
  • Genetic Pleiotropy*
  • Genome-Wide Association Study*
  • Genotyping Techniques
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Annotation
  • Observational Studies as Topic / statistics & numerical data
  • Osteoporosis / genetics
  • Polymorphism, Single Nucleotide
  • Racial Groups / genetics
  • Torso / anatomy & histology*