Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai 200093, China.
Sci China Life Sci. 2012 Jun;55(6):516-20. doi: 10.1007/s11427-012-4327-6. Epub 2012 Jun 29.
Lean body mass (LBM) and age at menarche (AAM) are two important complex traits for human health. The aim of this study was to identify pleiotropic genes for both traits using a powerful bivariate genome-wide association study (GWAS). Two studies, a discovery study and a replication study, were performed. In the discovery study, 909622 single nucleotide polymorphisms (SNPs) were genotyped in 801 unrelated female Han Chinese subjects using the Affymetrix human genome-wide SNP array 6.0 platform. Then, a bivariate GWAS was performed to identify the SNPs that may be important for LBM and AAM. In the replication study, significant findings from the discovery study were validated in 1692 unrelated Caucasian female subjects. One SNP rs3027009 that was bivariately associated with left arm lean mass and AAM in the discovery samples (P=7.26×10(-6)) and in the replication samples (P=0.005) was identified. The SNP is located at the upstream of DARC (Duffy antigen receptor for chemokines) gene, suggesting that DARC may play an important role in regulating the metabolisms of both LBM and AAM.
瘦体重(LBM)和初潮年龄(AAM)是影响人类健康的两个重要复杂特征。本研究旨在通过强大的双变量全基因组关联研究(GWAS)鉴定这两个特征的多效基因。本研究进行了两项研究,一项是发现研究,另一项是复制研究。在发现研究中,使用 Affymetrix 人类全基因组 SNP 芯片 6.0 平台,对 801 名无血缘关系的汉族女性进行了 909622 个单核苷酸多态性(SNP)的基因分型。然后,进行了双变量 GWAS,以鉴定可能对 LBM 和 AAM 重要的 SNP。在复制研究中,对来自发现研究的显著发现,在 1692 名无血缘关系的白种女性受试者中进行了验证。在发现样本(P=7.26×10(-6))和复制样本(P=0.005)中,一个 SNP rs3027009 与左臂瘦体重和 AAM 存在双变量关联,该 SNP 位于趋化因子受体(DARC)基因的上游,提示 DARC 可能在调节 LBM 和 AAM 的代谢中发挥重要作用。