Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density

Frontiers in Immunology

Hong-Wen Deng¹  Kuan-Jui Su¹  Chun-Ping Zeng²  Yu-Qian Song³  Shi-Di Hu³  Cheng Peng⁴  Hui-Ling Lou⁴  Wen-Xi Li⁴  Qiao-Cong Chen⁴  Hui-Hui Yuan⁴  Feng Liu⁴  Xu Lin⁵  Jie Shen⁵ 

[1] Center for Bioinformatics and Genomics, Department of Global Biostatistics and Data Science, Tulane University, New Orleans, LA, United States;Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China;Department of Geriatrics, National Key Clinical Specialty, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China;Shunde Hospital of Southern Medical University (The First People’s Hospital of Shunde), Foshan City, China;

关键词: appendicular lean mass;    bone mineral density;    pleiotropy;    genome wide association study;    novel SNPs;   

DOI  :  10.3389/fimmu.2021.643894

来源: DOAJ

【 摘 要 】

Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein–protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.

【 授权许可】

Unknown