A two-stage association study suggests BRAP as a susceptibility gene for schizophrenia.
Schizophrenia (SZ) is a neurodevelopmental disorder in which altered immune function typically plays an important role in mediating the effect of environmental insults and regulation of inflammation. The breast cancer suppressor protein associated protein (BRAP) is suggested to exert vital effects in neurodevelopment by modulating the mitogen-activated protein kinase cascade and inflammation signaling. To explore the possible role of BRAP in SZ, we conducted a two-stage study to examine the association of BRAP polymorphisms with SZ in the Han Chinese population. In stage one, we screened SNPs in BRAP from our GWAS data, which detected three associated SNPs, with rs3782886 being the most significant one (P  =  2.31E-6, OR  =  0.67). In stage two, we validated these three SNPs in an independently collected population including 1957 patients and 1509 controls, supporting the association of rs3782886 with SZ (P  =  1.43E-6, OR  =  0.73). Furthermore, cis-eQTL analysis indicates that rs3782886 genotypes are associated with mRNA levels of aldehyde dehydrogenase 2 family (ALDH2) (P  =  0.0039) and myosin regulatory light chain 2 (MYL2) (P < 1.0E-4). Our data suggest that the BRAP gene may confer vulnerability for SZ in Han Chinese population, adding further evidence for the involvement of developmental and/or neuroinflammatory cascades in the illness.
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China ; Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Fuquan
F
Zhang
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Chenxing
C
Liu
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
Yong
Y
Xu
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Guoyang
G
Qi
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Guozhen
G
Yuan
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Zaohuo
Z
Cheng
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Jidong
J
Wang
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Guoqiang
G
Wang
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Zhiqiang
Z
Wang
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Wei
W
Zhu
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Zhenhe
Z
Zhou
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Xingfu
X
Zhao
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Lin
L
Tian
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Chunhui
C
Jin
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Janmin
J
Yuan
Wuxi Mental Health Center of Nanjing Medical University, Wuxi, Jiangsu Province, China.
Guofu
G
Zhang
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Yaguang
Y
Chen
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Lifang
L
Wang
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Tianlan
T
Lu
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Hao
H
Yan
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Yanyan
Y
Ruan
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China.
Weihua
W
Yue
Key Laboratory of Mental Health, Ministry of Health, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China ; Peking-Tsinghua Center for Life Sciences, Beijing, China ; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Dai
D
Zhang
D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
C466107:MRLC2 protein, human; D018994:Myosin Light Chains; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases