TY  - JOUR
PY  - 2016//
TI  - Identification of SLC25A37 as a major depressive disorder risk gene
JO  - Journal of psychiatric research
A1  - Huo, Yong-Xia
A1  - Huang, Liang
A1  - Zhang, Deng-Feng
A1  - Yao, Yong-Gang
A1  - Fang, Yi-Ru
A1  - Zhang, Chen
A1  - Luo, Xiong-Jian
SP  - 168
EP  - 175
VL  - 83
IS  - 
N2  - 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.<br><br>Copyright © 2016 Elsevier Ltd. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 0022-3956
UR  - http://dx.doi.org/10.1016/j.jpsychires.2016.09.011
ID  - ref1
ER  -