Jian Xuemin, Chen Jianhua, Li Zhiqiang, Fahira Aamir, Shao Weihuan, Zhou Juan, Wang Ke, Wen Yanqin, Zhang Jinmai, Yang Qiangzhen, Pan Dun, Wang Zhuo, Shi Yongyong
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.
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 Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Dec 20;103:109973. doi: 10.1016/j.pnpbp.2020.109973. Epub 2020 May 22.
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.
多种遗传风险因素与精神疾病相关，这为这些疾病提供了遗传学见解；然而，这些疾病的病因仍然难以捉摸。15q13.3先前与精神分裂症、双相情感障碍和其他神经发育障碍有关。而编码范可尼贫血相关核酸酶1的FAN1被认为是与15q13.3相关的精神疾病的致病基因。本研究旨在调查FAN1与三种主要精神疾病的关联。在此，我们对中国汉族人群进行了一项病例对照研究。在1248例精神分裂症患者、1344例双相情感障碍患者、1056例重度抑郁症患者和1248例正常对照中对FAN1的三个单核苷酸多态性（SNP）进行了基因分型。我们发现SNP rs7171212与双相情感障碍（p = 0.023，p = 0.022，OR = 0.658）和精神分裂症（p = 0.021，p = 0.019，OR = 0.645）相关。而rs4779796与精神分裂症相关（p = 0.001，校正p = 0.003，OR = 1.089）。此外，rs7171212（校正p = 0.018，校正p = 0.018，OR = 0.652）和rs4779796（校正p = 0.024，OR = 1.12）与精神分裂症和双相情感障碍的合并病例显著相关。进一步，对病例对照数据和从先前报道的全基因组关联研究中提取的数据集进行了荟萃分析，以验证这些有前景的SNP。我们的结果提供了新的证据，表明FAN1可能是汉族人群中精神分裂症和双相情感障碍的常见易感基因。这些新发现需要通过更大样本量和功能表征进行进一步验证，以了解FAN1在精神分裂症和双相情感障碍患病率中潜在的致病机制。
