title: Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study.
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.
authors.affiliation: School of Basic Medical Science, Institute of Bioinformatics, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Zhang
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Xiang-Lei
authors.initials: XL
authors.lastname: Peng
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000378:metabolism*; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism*; D009929:Organ Size; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000217:Acyltransferases; C020680:glycine acyltransferase