Search

Bone mineral density (BMD) and whole‐body lean mass (WBLM) are two important phenotypes of osteoporosis and sarcopenia. Previous studies have shown that BMD and lean mass were phenotypically and genetically correlated. To identify the novel common genetic factors shared between BMD and WBLM, we performed the conditional false discovery rate (cFDR) analysis using summary data of the genome‐wide association study of femoral neck BMD (n = 53,236) and WBLM (n = 38,292) from the Genetic Factors for Osteoporosis Consortium (GEFOS). We identified eight pleiotropic Single Nucleotide Polymorphism (SNPs) (PLCL1 rs11684176 and rs2880389, JAZF1 rs198, ADAMTSL3 rs10906982, RFTN2/MARS2 rs7340470, SH3GL3 rs1896797, ST7L rs10776755, ANKRD44/SF3B1 rs11888760) significantly associated with femoral neck BMD and WBLM (ccFDR < 0.05). Bayesian fine‐mapping analysis showed that rs11888760, rs198, and rs1896797 were the possible functional variants in the ANKRD44/SF3B1, JAZF1i, and SH3GL3 loci, respectively. Functional annotation suggested that rs11888760 was likely to comprise a DNA regulatory element and linked to the expression of RFTN2 and PLCL1. PLCL1 showed differential expression in laryngeal posterior cricoarytenoid muscle between rats of 6 months and 30 months of age. Our findings, together with PLCL1's potential functional relevance to bone and skeletal muscle function, suggested that rs11888760 was the possible pleiotropic functional variants appearing to coregulate both bone and muscle metabolism through regulating the expression of PLCL1. The findings enhanced our knowledge of genetic associations between BMD and lean mass and provide a rationale for subsequent functional studies of the implicated genes in the pathophysiology of diseases, such as osteoporosis and sarcopenia. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies suggested that long noncoding RNAs (lncRNAs) were widely transcribed in the genome, but their potential roles in the genetic complexity of human disorders required further exploration. The purpose of the present study was to explore genetic polymorphisms of lncRNAs associated with bone mineral density (BMD) and its potential value. Based on the lncRNASNP database, 55,906 lncSNPs were selected to conduct a genome‐wide association study meta‐analysis among 11,140 individuals of seven independent studies for BMDs at femoral neck (FN), lumbar spine, and total hip (HIP). Promising results were replicated in Genetic Factors for Osteoporosis Consortium (GEFOS Sequencing, n = 32,965). We found two lncRNA loci that were significantly associated with BMD. MEF2C antisense RNA 1 (MEF2C‐AS1) located at 5q14.3 was significantly associated with FN‐BMD after Bonferroni correction, and the strongest association signal was detected at rs6894139 (P = 3.03 × 10−9). LOC100506136 rs6465531 located at 7q21.3 showed significant association with HIP‐BMD (P = 7.43 × 10−7). MEF2C‐AS1 rs6894139 was replicated in GEFOS Sequencing with P‐value of 1.43 × 10−23. Our results illustrated the important role of polymorphisms in lncRNAs in determining variations of BMD and provided justification and evidence for subsequent functional studies. [ABSTRACT FROM AUTHOR]