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Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study |
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| Authors: | Yan-Fang Guo Li-Shu Zhang Yong-Jun Liu Hong-Gang Hu Jian Li Qing Tian Ping Yu Feng Zhang Tie-Lin Yang Yan Guo Xiang-Lei Peng Meng Dai Wei Chen Hong-Wen Deng |
| Institution: | 1. School of Basic Medical Science, Institute of Bioinformatics, Southern Medical University, Guangzhou, 510515, People’s Republic of China 2. School of Science, College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, People’s Republic of China 3. Department of Biostatistics, School of Public Health and Tropical Medicine, Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, 70112, USA 4. The Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China 5. Department of Epidemiology, School of Public Health and Tropical Medicine, Center for Cardiovascular Health, Tulane University, New Orleans, LA, 70112, USA 6. Center of System Biomedical Sciences, Shanghai University of Science and Technology, Shanghai, 200093, People’s Republic of China |
| Abstract: | Bone and muscle, two major tissue types of musculoskeletal system, have strong genetic determination. Abnormality in bone and/or muscle may cause musculoskeletal diseases such as osteoporosis and sarcopenia. Bone size phenotypes (BSPs), such as hip bone size (HBS), appendicular bone size (ABS), are genetically correlated with body lean mass (mainly muscle mass). However, the specific genes shared by these phenotypes are largely unknown. In this study, we aimed to identify the specific genes with pleiotropic effects on BSPs and appendicular lean mass (ALM). We performed a bivariate genome-wide association study (GWAS) by analyzing ~690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) followed by a replication study in 2,286 unrelated US Caucasians (558 males and 1,728 females). We identified 14 interesting single nucleotide polymorphisms (SNPs) that may contribute to variation of both BSPs and ALM, with p values <10?6 in discovery stage. Among them, the association of three SNPs (rs2507838, rs7116722, and rs11826261) in/near GLYAT (glycine-N-acyltransferase) gene was replicated in US Caucasians, with p values ranging from 1.89 × 10?3 to 3.71 × 10?4 for ALM–ABS, from 5.14 × 10?3 to 1.11 × 10?2 for ALM–HBS, respectively. Meta-analyses yielded stronger association signals for rs2507838, rs7116722, and rs11826261, with pooled p values of 1.68 × 10?8, 7.94 × 10?8, 6.80 × 10?8 for ALB–ABS and 1.22 × 10?4, 9.85 × 10?5, 3.96 × 10?4 for ALM–HBS, respectively. Haplotype allele ATA based on these three SNPs was also associated with ALM–HBS and ALM–ABS in both discovery and replication samples. Interestingly, GLYAT was previously found to be essential to glucose metabolism and energy metabolism, suggesting the gene’s dual role in both bone development and muscle growth. Our findings, together with the prior biological evidence, suggest the importance of GLYAT gene in co-regulation of bone phenotypes and body lean mass. |
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