全基因组关联分析显示基因ANXA8和C10orf11为影响肌少症的候选基因

为了寻找与瘦体重(lean body mass,LBM)相关的单核苷酸多态性(single nucleotide polymorphism, SNP)位点及易感基因,在1 000个不相关的白人中采用Affymetix 500K芯片扫描了500 000个SNPs,并进行全基因组关联分析(genome-wide association study,GWAS),显著结果在1 625个中国人样本和2 283个欧洲白人样本中进行验证,并将验证结果与研究结果进行荟萃分析。研究发现SNPsrs7905603,rs9416083,rs4409772,rs2894310与LBM关联,其中rs7905603位于基因ANXA8,其他3个SNPs位于基因C10orf11。荟萃分析得到的合并p值分别为2.08×10-5,7.44×10~(-6),6.73×10~(-6),6.76×10~(-6)。ANXA8和C10orf11基因是影响LBM变异的候选基因,这对肌少症的认识提供了新的理论依据。

Genome-wide association analysis identifying that genes ANXA8 and C10orf11 are candidate genes for sarcopenia

Sarcopenia is a complex polygenic disease characterized by decreased muscle mass, muscle strength and muscle function. Genetic factors play a crucial role in muscle. However, most of the genetic factors have not been identified. Lean body mass (LBM), mainly composed of skeletal muscle, is an important factor in the diagnosis of sarcopenia, and it is a complex trait influenced by environmental and genetic factors. To find single nucleotide polymorphisms (SNPs) loci and susceptibility genes associated with LBM, the Affymetrix 500K chip for genotyping was used to scan 500 000 SNPs in 1 000 American Caucasian samples. Genome-wide association study (GWAS) was used to replicate the significant results in 1 625 Chinese samples and 2 283 European white samples, and a meta-analysis of the validation results and GWAS results was performed. The SNPs rs7905603,rs9416083, rs4409772, and rs2894310 were found to be associated with LBM, SNP rs7905603 was located in ANXA8 gene, and the other three SNPs were located in C10orf11 gene. The combined p-values of meta-analysis were 2.08×10^-5, 7.44×10^-6, 6.73×10^-6, and 6.76×10^-6, respectively. Our results suggest that ANXA8 and C10orf11 genes are important genes affecting LBM variation, which provides a new theoretical basis for the understanding of sarcopenia.