Pleiotropic genomic variants at 17q21.31 associated with bone mineral density and body fat mass: a bivariate genome-wide association analysis

Eur J Hum Genet. 2021 Apr;29(4):553-563. doi: 10.1038/s41431-020-00727-3. Epub 2020 Sep 22.

Abstract

Osteoporosis and obesity are two severe complex diseases threatening public health worldwide. Both diseases are under strong genetic determinants as well as genetically correlated. Aiming to identify pleiotropic genes underlying obesity and osteoporosis, we performed a bivariate genome-wide association (GWA) meta-analysis of hip bone mineral density (BMD) and total body fat mass (TBFM) in 12,981 participants from seven samples, and followed by in silico replication in the UK biobank (UKB) cohort sample (N = 217,822). Combining the results from discovery meta-analysis and replication sample, we identified one novel locus, 17q21.31 (lead SNP rs12150327, NC_000017.11:g.44956910G > A, discovery bivariate P = 4.83 × 10-9, replication P = 5.75 × 10-5) at the genome-wide significance level (ɑ = 5.0 × 10-8), which may have pleiotropic effects to both hip BMD and TBFM. Functional annotations highlighted several candidate genes, including KIF18B, C1QL1, and PRPF19 that may exert pleiotropic effects to the development of both body mass and bone mass. Our findings can improve our understanding of the etiology of osteoporosis and obesity, as well as shed light on potential new therapies.

Publication types

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

MeSH terms

  • Aged
  • Bone Density / genetics
  • Chromosomes, Human, Pair 17 / genetics*
  • Complement C1q / genetics
  • DNA Repair Enzymes / genetics
  • Female
  • Genetic Pleiotropy*
  • Humans
  • Kinesins / genetics
  • Middle Aged
  • Nuclear Proteins / genetics
  • Obesity / genetics*
  • Osteoporosis / genetics*
  • Polymorphism, Single Nucleotide*
  • RNA Splicing Factors / genetics

Substances

  • C1QL1 protein, human
  • Nuclear Proteins
  • RNA Splicing Factors
  • Complement C1q
  • KIF18B protein, human
  • Kinesins
  • DNA Repair Enzymes
  • PRPF19 protein, human