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Original Research

Polymorphisms and Haplotypes in the YWHAE Gene Increase Susceptibility to Bipolar Disorder in Chinese Han Population

Jie Liu, PhD; Zhi-Qiang Li, PhD; Jun-Yan Li, PhD; Tao Li, PhD; Ti Wang, PhD; You Li, PhD; Yi-Feng Xu, PhD; Guo-Yin Feng, BS; Yong-Yong Shi, PhD; and Lin He, PhD

Published: October 15, 2012

Article Abstract

Background: Schizophrenia and bipolar disorder are 2 major psychiatric illnesses sharing some specific genetic risk factors. Increasing evidence suggests the 2 illnesses might be more closely related than previously considered.

Objective: To test this hypothesis, we investigated the allele and genotype frequencies of 11 single nucleotide polymorphisms (SNPs) and the haplotypes in these SNPs of the YWHAE gene.

Method: 1,982 patients were interviewed by 2 independent, experienced psychiatrists. Bipolar disorder diagnoses were made in strict accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria using the Structured Clinical Interview for DSM-IV Axis I Disorders. In 2011, we conducted this genetic association analysis between 11 SNPs in YWHAE and bipolar disorder, involving a male group and a female group.

Results: In the analysis of allele and genotype frequencies, the SNP rs1873827 increased susceptibility to bipolar disorder in the male group. The haplotype analysis of CAC in rs3752826, rs2131431, and rs1873827 in the male group (χ2=25.744, P=3.97E-07, OR=0.478 [95% CI, 0.358-0.639]) and of ACT and CAC in rs3752826, rs2131431, and rs1873827 in the female group (for ACT, χ2=30.365, P=3.67E-08, OR=0.040 [95% CI, 0.007-0.218]; for CAC, χ2=16.874, P=4.04E-05, OR=0.597 [95% CI, 0.466-0.765]) showed they are protective factors for bipolar disorder. However, the haplotype analysis of CAT in the male group (χ2=19.874, P=8.39E-06, OR=2.314 [95% CI, 1.587-3.374]) and of AAC and CAT in the female group (for AAC, χ2=38.561, P=5.47E-10, OR=7.104 [95% CI, 3.471-14.540]; for CAT, χ2=25.497, P=4.52E-07, OR=2.076 [95% CI, 1.556-2.770]) showed they are risk factors for bipolar disorder.

Conclusions: Considering the size of our sample, the results suggest that YWHAE does play a major role in bipolar disorder in the Han Chinese population.

J Clin Psychiatry 2012;73(10):e1276-e1282

Submitted: April 3, 2012; accepted June 25, 2012 (doi:10.4088/JCP.12m07824).

Corresponding author: Lin He, PhD, Bio-X Institutes, Shanghai Jiao Tong University, The Central Little White House, 1954 Huashan Rd, Shanghai 200030, P.R.China (

Volume: 73

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