Common variants in FAN1, located in 15q13.3, confer risk for schizophrenia and bipolar disorder in Han Chinese.

Prog Neuropsychopharmacol Biol Psychiatry

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) and the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai 200030, PR China; Shanghai Key laboratory of Sleep Disordered Breathing, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; Affiliated Hospital of Qingdao University, Biomedical Sciences Institute of Qingdao University, (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, Shandong 266003, PR China; Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200030, PR China; Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai 200030, PR China; Shanghai Changning Mental Health Center, Shanghai 200030, PR China; Department of Psychiatry, First Teaching Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, PR China. Electronic address:

Published: December 2020

Multiple genetic risk factors have been associated with psychiatric disorders which provides the genetic insight to these disorders; however, the etiology of these disorders is still elusive. 15q13.3 was previously associated with schizophrenia, bipolar and other neurodevelopmental disorders. Whereas, the FAN1 which encodes the Fanconi anemia associated nuclease 1 was suggested to be causal gene for 15q13.3 related psychiatric disorders. This study aimed to investigate the association of FAN1 with three major psychiatric disorders. Herein, we conducted a case-control study with the Chinese Han population. Three single nucleotide polymorphisms (SNPs) of FAN1 were genotyped in 1248 schizophrenia cases, 1344 bipolar disorder cases, 1056 major depressive disorder cases and 1248 normal controls. We found that SNPs rs7171212 was associated with bipolar (p = 0.023, p = 0.022, OR = 0.658) and schizophrenia (p = 0.021, p = 0.019, OR = 0.645). Whereas, rs4779796 was associated with schizophrenia (p = 0.001, adjusted p = 0.003, OR = 1.089). In addition, rs7171212 (adjusted p = 0.018, adjusted p = 0.018, OR = 0.652) and rs4779796 (adjusted p = 0.024, OR = 1.12) showed significantly associated with combined cases of schizophrenia and bipolar disorder. Further, meta-analysis was performed with the case-control data and dataset extracted from previously reported genome-wide association study to validate the promising SNPs. Our results provide the new evidence that FAN1 may be a common susceptibility gene for schizophrenia and bipolar disorder in Han Chinese. These novel findings need further validation with larger sample size and functional characterization to understand the underlying pathogenic mechanism behind FAN1 in the prevalence of schizophrenia and bipolar disorders.

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http://dx.doi.org/10.1016/j.pnpbp.2020.109973DOI Listing

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