Identification of SLC25A37 as a major depressive disorder risk gene

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• 作者：Yong-Xia Huo^a ; ¹ ; Liang Huang^b ; ¹ ; Deng-Feng Zhang^a ; Yong-Gang Yao^a ; Yi-Ru Fang^c ; Chen Zhang^c ; ^{zhangchen645@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Xiong-Jian Luo^a ; ^{luoxiongjian@mail.kiz.ac.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Major depressive disorder (MDD) ; SLC25A37 ; Genetic association ; Expression quantitative trait loci (eQTL) ; Integrative analysis ; Expression
• 刊名：Journal of Psychiatric Research
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：168-175
• 全文大小：614 K

文摘

Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders, but the genetic etiology remains largely unknown. We performed a meta-analysis (14,543 MDD cases and 14,856 controls) through combining the GWAS data from the Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium and the CONVERGE consortium and identified seven SNPs (four of them located in the downstream of SCL25A37) that showed suggestive associations (P < 5.0 × 10⁻⁷) with MDD. Systematic integration (Sherlock integrative analysis) of brain eQTL and GWAS meta-analysis identified SCL25A37 as a novel MDD risk gene (P = 2.22 × 10⁻⁶). A cis SNP (rs6983724, ∼28 kb downstream of SCL25A37) showed significant association with SCL25A37 expression (P = 1.19 × 10⁻⁹) and suggestive association with MDD (P = 1.65 × 10⁻⁷). We validated the significant association between rs6983724 and SCL25A37 expression in independent expression datasets. Finally, we found that SCL25A37 is significantly down-regulated in hippocampus and blood of MDD patients (P = 3.49 × 10⁻³ and P = 2.66 × 10⁻¹³, respectively). Our findings implicate that the SCL25A37 is a MDD susceptibility gene whose expression may influence MDD risk. The consistent down-regulation of SCL25A37 in MDD patients in three independent samples suggest that SCL25A37 may be used as a potential biomarker for MDD diagnosis. Further functional characterization of SCL25A37 may provide a potential target for future therapeutics and diagnostics.