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

• Published in: Journal of human genetics Vol. 66; no. 3; pp. 251 - 260
• Main Authors: Feng, Gui-Juan, Wei, Xin-Tong, Zhang, Hong, Yang, Xiao-Lin, Shen, Hui, Tian, Qing, Deng, Hong-Wen, Zhang, Lei, Pei, Yu-Fang
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.03.2021
• Subjects: Adult; Aged; Body Composition - genetics; Body mass; Bone density; Bone Density - genetics; Bone mass; Bone mineral density; Cohort Studies; Ethnicity - genetics; Female; Femur - chemistry; Genetic Heterogeneity; Genetic Pleiotropy; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotyping Techniques; Heritability; Hip; Humans; Lean body mass; Male; Middle Aged; Molecular Sequence Annotation; Observational Studies as Topic - statistics & numerical data; Osteoporosis - genetics; Polymorphism, Single Nucleotide; Racial Groups - genetics; Replication; Single-nucleotide polymorphism; Torso - anatomy & histology
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-020-00835-4

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 ) 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 , replication p = 1.95 × 10 ) and 18q21.32 (rs489693, discovery p = 1.67 × 10 , replication p = 1.17 × 10 ). 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.