Genome wide association study: searching for genes underlying body mass index 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=5.45×10⁻⁷-7.26×10⁻⁶, 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).


CONCLUSIONS
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.
Department of Epidemiology and Biostatistics, School of Public Health, Central South University, Changsha 410078, Hunan, China.
Fang
F
Yang
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China.
Xiang Ding
XD
Chen
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China.
Li Jun
LJ
Tan
Department of Endocrinology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, China.
Jie
J
Shen
Department of Pediatrics, University of Missouri Kansas City School of Medicine, Division of Gastroenterology, Children's Mercy Hospital, Kansas City, Missouri 64108, USA.
Ding You
DY
Li
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China.
Fang
F
Zhang
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China.
Bao Yong
BY
Sha
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China; Systematic Biomedicine Research Center, University of Shanghai for Science and Technology, Shanghai 200093, China; Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA.
Hong Wen
HW
Deng
D000368:Aged; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
C529271:EIF2AK4 protein, human; D017346:Protein Serine-Threonine Kinases
Body mass index; EIF2AK4; Genome wide association; Replication