The YWHAE gene confers risk to major depressive disorder in the male group of Chinese Han population

Schizophrenia and major depressive disorder are two major psychiatric illnesses that may share specific genetic risk factors to a certain extent. Increasing evidence suggests that the two disorders might be more closely related than previously considered. To investigate whether YWHAE gene plays a significant role in major depressive disorder in Han Chinese population, we recruited 1135 unrelated major depressive disorder patients (485 males, 650 females) and 989 unrelated controls (296 males, 693 females) of Chinese Han origin. Eleven common SNPs were genotyped using TaqMan® technology. In male-group, the allele and genotype frequencies of rs34041110 differed significantly between patients and control (P_allele=0.036486, OR[95%CI]: 1.249442(1.013988-1.539571); P_genotype=0.045301). Also in this group, allele and genotype frequencies of rs1532976 differed significantly (P_allele=0.013242, OR[95%CI]: 1.302007(1.056501-1.604563); genotype: P=0.039152). Haplotype-analyses showed that, in male-group, positive association with major depressive disorder was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ²=20.397, P=6.38E-06, OR[95%CI]: 7.442 [2.691-20.583]), its C-A-C-G haplotype (χ²=19.122, P=1.24E-05, OR and 95%CI: 0.402 [0.264-0.612]), its C-C-T-G haplotype (χ²=9.766, P=0.001785, OR[95%CI]: 5.654 [1.664-19.211]). In female-group, positive association was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ²=78.628, P=7.94E-19, OR[95%CI]: 50.043 [11.087-225.876]), its A-C-T-G haplotype (χ²=38.806, P=4.83E-10, OR[95%CI]: 0.053 [0.015-0.192]), the C-A-C-G haplotype (χ²=18.930, P=1.37E-05, OR[95%CI]: 0.526 [0.392-0.705]), and the C-C-T-G haplotype (χ²=38.668, P=5.18E-10, OR[95%CI]: 6.130 [3.207-11.716]). Our findings support YWHAE being a risk gene for Major Depressive Disorder in the Han Chinese population.