Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study - PubMed (original) (raw)

. 2013 Feb;132(2):189-99.

doi: 10.1007/s00439-012-1236-5. Epub 2012 Oct 30.

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

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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

Yan-Fang Guo et al. Hum Genet. 2013 Feb.

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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Figures

Fig. 1

Fig. 1

Distribution of p values across the genome in bivariate association analyses in Chinese sample. The p values are plotted according to its physical position on successive chromosomes. The dashed lines represent association signals with p = 1.00E-05. ALM appendicular lean mass, HBS hip bone size, ABS appendicular bone size.

Fig. 2

Fig. 2

Haplotype blocks for the two groups of consecutive SNPs located on chromosome 4 and 11. The LD pattern (D′) and haplotype frequency for each block were analyzed and plotted using the Haploview program.

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