Genome wide association study: searching for genes underlying body mass index in the Chinese.

Fang Yang; Xiang Ding Chen; Li Jun Tan; Jie Shen; Ding You LI; Fang Zhang; Bao Yong Sha; Hong Wen Deng

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Genome wide association study: searching for genes underlying body mass index in the Chinese.

Author: Fang YANG ¹ ; Xiang Ding CHEN ² ; Li Jun TAN ² ; Jie SHEN ³ ; Ding You LI ⁴ ; Fang ZHANG ² ; Bao Yong SHA ² ; Hong Wen DENG ⁵ ;
Author Information

1. Department of Epidemiology and Biostatistics, School of Public Health, Central South University, Changsha 410078, Hunan, China.
2. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China.
3. Department of Endocrinology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, China.
4. Department of Pediatrics, University of Missouri Kansas City School of Medicine, Division of Gastroenterology, Children's Mercy Hospital, Kansas City, Missouri 64108, USA.
5. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China
Publication Type:Journal Article
Keywords: Body mass index; EIF2AK4; Genome wide association; Replication
MeSH: Aged; Asian Continental Ancestry Group; genetics; Body Mass Index; China; epidemiology; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Middle Aged; Obesity; ethnology; genetics; Polymorphism, Single Nucleotide; Protein-Serine-Threonine Kinases; genetics
From: Biomedical and Environmental Sciences 2014;27(5):360-370
CountryChina
Language:English
Abstract:
OBJECTIVEObesity 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.
METHODSAffymetrix 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.
RESULTSEight SNPs were significantly associated with BMI variation after false discovery rate (FDR) correction (P=5.45×10⁻⁷-7.26×10⁻⁶, 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 & 4.39×10⁻⁶, 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).
CONCLUSIONOur 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.