Genome Wide Association Study: Searching for Genes Underlying Body Mass Index in the Chinese  

作　　者：YANG Fang CHEN Xiang Ding TAN Li Jun SHEN Jie LI Ding You ZHANG Fang SHA Bao Yong DENG Hong Wen 

机构地区：[1]Department of Epidemiology and Biostatistics, School of Public Health, Central South University [2]Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University [3]Department of Endocrinology, The Third Affiliated Hospital of Southern Medical University [4]Department of Pediatrics,University of Missouri Kansas City School of Medicine, Division of Gastroenterology, Children's Mercy Hospital [5]Systematic Biomedicine Research Center, University of Shanghai for Science and Technology [6]Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University

出　　处：《Biomedical and Environmental Sciences》2014年第5期360-370,共11页生物医学与环境科学（英文版）

基　　金：supported by grants from Natural Science Foundation of China(30600364,30470534,30771222,30731160618,30230210,and 81101655);the grant from the China Postdoctoral Science Foundation(2011M501282)

摘　　要：Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate （FDR） correction （P=5.45×10-7-7.26×106, FDR q=0.033-0.048）. Two adjacent SNPs （rs4432245 ＆ rs711906） in the eukaryotic translation initiation factor 2 alpha kinase 4 （EIF2AK4） gene were significantly associated with BMI （P=6.38×10-6＆ 4.39×106, FDR q=0.048）. In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene （P=0.03 ＆ 0.01, respectively）. Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ＇ethnic specific＇ in the Chinese.Objective Obesity is becoming a worldwide health problem. The genome wide association （GWA） study particularly for body mass index （BMI） has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed. Methods Affymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281 533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software. Results Eight SNPs were significantly associated with BMI variation after false discovery rate （FDR） correction （P=5.45×10-7-7.26×106, FDR q=0.033-0.048）. Two adjacent SNPs （rs4432245 ＆ rs711906） in the eukaryotic translation initiation factor 2 alpha kinase 4 （EIF2AK4） gene were significantly associated with BMI （P=6.38×10-6＆ 4.39×106, FDR q=0.048）. In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene （P=0.03 ＆ 0.01, respectively）. Conclusion Our study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be ＇ethnic specific＇ in the Chinese.

关 键 词：Body mass index Genome wide association EIF2AK4 REPLICATION 

分 类 号：R440[医药卫生—诊断学]