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Abstract
We conducted a cross-trait meta-analysis of genome-wide association study on schizophrenia (SCZ) (n = 65,967), bipolar disorder (BD) (n = 41,653), autism spectrum disorder (ASD) (n = 46,350), attention deficit hyperactivity disorder (ADHD) (n = 55,374), and depression (DEP) (n = 688,809). After the meta-analysis, the number of genomic loci increased from 14 to 19 in ADHD, from 3 to 10 in ASD, from 45 to 57 in DEP, from 8 to 54 in BD, and from 64 to 87 in SCZ. We observed significant enrichment of overlapping genes among different disorders and identified a panel of cross-disorder genes. A total of seven genes were found being commonly associated with four out of five psychiatric conditions, namely GABBR1, GLT8D1, HIST1H1B, HIST1H2BN, HIST1H4L, KCNB1, and DCC. The SORCS3 gene was highlighted due to the fact that it was involved in all the five conditions of study. Analysis of correlations unveiled the existence of two clusters of related psychiatric conditions, SCZ and BD that were separate from the other three traits, and formed another group. Our results may provide a new insight for genetic basis of the five psychiatric disorders.
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1 West China Hospital of Sichuan University, Mental Health Center and Psychiatric Laboratory, State Key Laboratory of Biotherapy, Chengdu, China (GRID:grid.412901.f) (ISNI:0000 0004 1770 1022); West China Hospital of Sichuan University, West China Brain Research Center, Chengdu, China (GRID:grid.412901.f) (ISNI:0000 0004 1770 1022)
2 First Clinical Medical College/First Hospital of Shanxi Medical University, Department of Psychiatry, Taiyuan, China (GRID:grid.263452.4) (ISNI:0000 0004 1798 4018)
3 George Mason University (GMU), School of Systems Biology, Fairfax, USA (GRID:grid.22448.38) (ISNI:0000 0004 1936 8032); Research Centre for Medical Genetics, Moscow, Russia (GRID:grid.415876.9)
4 Massachusetts General Hospital, Analytic and Translational Genetics Unit, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Broad Institute of Harvard and MIT, Stanley Center for Psychiatric Research, Cambridge, USA (GRID:grid.66859.34)
5 Shanghai Jiaotong University, Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
6 Southwest Jiaotong University, School of Life Science and Engineering, Chengdu, China (GRID:grid.263901.f) (ISNI:0000 0004 1791 7667)
7 West China Hospital of Sichuan University, The Center of Gerontology and Geriatrics, Chengdu, China (GRID:grid.412901.f) (ISNI:0000 0004 1770 1022)
8 Affiliated to Nanjing Medical University, Department of Geriatric Psychiatry, Nanjing Brain Hospital, Nanjing, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)
9 Fudan University, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443)
10 The Affiliated Brain Hospital of Nanjing Medical University, Department of Psychiatry, Nanjing, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)
11 Shanghai Jiaotong University, Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293); Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)