title: Identification of SLC25A37 as a major depressive disorder risk gene.
abstract: 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 × 10-3and 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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Yong-Xia
authors.initials: YX
authors.lastname: Huo
authors.affiliation: First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi-Ru
authors.initials: YR
authors.lastname: Fang
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zhangchen645@gmail.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China. Electronic address: luoxiongjian@mail.kiz.ac.cn.
authors.forename: Xiong-Jian
authors.initials: XJ
authors.lastname: Luo
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D027682:Cation Transport Proteins / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D005838:Genotype; D024101:Mitochondrial Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk
chemical_list: D027682:Cation Transport Proteins; D024101:Mitochondrial Proteins; C561492:Slc25a37 protein, human
keywords: Expression; Expression quantitative trait loci (eQTL); Genetic association; Integrative analysis; Major depressive disorder (MDD); SLC25A37