title: A Genome-Wide Association Study Uncovers a Genetic Locus Associated with Thoracic-to-Hip Ratio in Koreans.
abstract: The thoracic-to-hip circumference ratio (THR) is an anthropometric marker recently described as a predictor of type 2 diabetes. In this study, we performed a genome-wide association study (GWAS) followed by confirmatory analyses to identify genetic markers associated with THR. A total of 7,240 Korean subjects (4,988 for the discovery stage and 2,252 for the confirmatory analyses) were recruited for this study, and genome-wide single nucleotide polymorphism (SNP) genotyping of the initial 4,988 individuals was performed using Affymetrix Human SNP array 5.0. Linear regression analysis was then performed to adjust for the effects of age, sex, and current diabetes medication status on the THR of the study subjects. In the initial discovery stage, there was a statistically nominal association between minor alleles of SNP markers on chromosomes 4, 8, 10, and 12, and THR changes (p < 5.0 × 10-6). The subsequent confirmatory analyses of these markers, however, only detected a significant association between two SNPs in the HECTD4 gene and decreased THRs. Notably, this association was detected in male (rs11066280: p = 1.14 × 10-2; rs2074356: p = 1.10 × 10-2), but not in female subjects. Meanwhile, the combined results from the two analyses (initial and confirmatory) indicated that minor alleles of these two intronic variants exhibited a significant genome-wide association with decreased THR in the male subjects (n = 3,155; rs11066280: effect size = -0.008624, p = 6.19 × 10-9; rs2074356: effect size = -0.008762, p = 1.89 × 10-8). Furthermore, minor alleles of these two SNPs exhibited protective effects on patients' risks for developing type 2 diabetes. In conclusion, we have identified two genetic variations in HECTD4 that are associated with THR, particularly in men.
authors.affiliation: Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon 34054, Republic of Korea.
authors.forename: Seongwon
authors.initials: S
authors.lastname: Cha
authors.affiliation: Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon 34054, Republic of Korea.
authors.forename: Ah Yeon
authors.initials: AY
authors.lastname: Park
authors.affiliation: Department of Biology and Research Institute of Basic Sciences, College of Natural Sciences, Sungshin Women's University, Seoul, 01133, Republic of Korea.
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kang
mesh_terms: D000368:Aged; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D055106:Genome-Wide Association Study; D006615:Hip / Q000033:anatomy & histology* / Q000254:growth & development; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012737:Sex Factors; D013909:Thorax / Q000033:anatomy & histology* / Q000254:growth & development; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases