机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of theChinese Academy of Sciences and Yunnan Province, Kunming Institute ofZoology, Kunming, Yunnan, China[2]Kunming College of Life Science,University of Chinese Academy of Sciences, Kunming, Yunnan, China[3]Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang,China[4]Shanghai Mental Health Center, Shanghai Jiao Tong University Schoolof Medicine, Shanghai, China[5]Jinhua Second Hospital, Jinhua, Zhejiang, China[6]Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou,Zhejiang, China[7]Hangzhou Seventh People’s Hospital, Hangzhou, Zhejiang,China[8]Department of Psychiatry, the First Affiliated Hospital of KunmingMedical University, Kunming, Yunnan, China[9]Wuhan Institute forNeuroscience and Neuroengineering, South-Central University for Nationalities,Wuhan, Hubei, China[10]Chinese Brain Bank Center, Wuhan, Hubei, China[11]CASCenter for Excellence in Brain Science and Intelligence Technology, ChineseAcademy of Sciences, Shanghai, China
Genetic analyses of psychiatric illnesses, such as bipolar disorder (BPD), have revealed essential information regarding the underlying pathological mechanisms. While such studies in populations of European ancestry have achieved prominent success, understanding the genetic risk factors of these illnesses (especially BPD) in Chinese population remains an urgent task. Given the lack of genome-wide association study (GWAS) of BPD in Chinese population from Mainland China, replicating the previously reported GWAS hits in distinct populations will provide valuable information for future GWAS analysis in Han Chinese. In the present study, we have recruited 1146 BPD cases and 1956 controls from Mainland China for genetic analyses, as well as 65 Han Chinese brain amygdala tissues for mRNA expression analyses. Using this clinical sample, one of the largest Han Chinese BPD samples till now, we have conducted replication analyses of 21 single nucleotide polymorphisms (SNPs) extracted from previous GWAS of distinct populations. Among the 21 tested SNPs, 16 showed the same direction of allelic effects in our samples compared with previous studies; 6 SNPs achieved nominal significance (p < 0.05) at one-tailed test, and 2 additional SNPs showed marginal significance (p < 0.10). Aside from replicating previously reported BPD risk SNPs, we herein also report several intriguing findings: (1) the SNP rs174576 was associated with BPD in our Chinese sample and in the overall global meta-analysis, and was significantly correlated with FADS1 mRNA in diverse public RNA-seq datasets as well as our in house collected Chinese amygdala samples; (2) two (partially) independent SNPs in MAD1L1 were both significantly associated with BPD in our Chinese sample, which was also supported by haplotype analysis; (3) a rare SNP rs78089757 in 10q26.13 region was a genome-wide significant variant for BPD in East Asians, and this SNP was near monomorphic in Europeans. In sum, these results confirmed several significant BPD risk genes. We hope this Chinese BPD case-control sample and the current brain amygdala tissues (with continuous increasing sample size in the near future) will provide helpful resources in elucidating the genetic and molecular basis of BPD in this major world population.
基金：
Strategic Priority Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [XDB13000000]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81722019, 31701133, 31701088, 81471358, 81771450]; medical and health science and technology project in Zhejiang [2018KY721]; Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20152530]; Shanghai Municipal Commission of Health and Family Planning Foundation, Key Developing Disciplines [2015ZB0405]; Yunnan Provincial Science and Technology Department-Kunming Medical University Joint Applied Basic Research Project [2015FB031]; Health Science and Technology Plan projects in Yunnan Province [2017NS028]; West China Psychiatric Association; Chinese Academy of Sciences Western Light Program; Youth Innovation Promotion Association, CAS; CAS Pioneer Hundred Talents Program; 1000 Young Talents ProgramChinese Academy of Sciences
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of theChinese Academy of Sciences and Yunnan Province, Kunming Institute ofZoology, Kunming, Yunnan, China[2]Kunming College of Life Science,University of Chinese Academy of Sciences, Kunming, Yunnan, China
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of theChinese Academy of Sciences and Yunnan Province, Kunming Institute ofZoology, Kunming, Yunnan, China[11]CASCenter for Excellence in Brain Science and Intelligence Technology, ChineseAcademy of Sciences, Shanghai, China
推荐引用方式(GB/T 7714)：
Zhao Lijuan,Chang Hong,Zhou Dong-Sheng,et al.Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population[J].TRANSLATIONAL PSYCHIATRY.2018,8:doi:10.1038/s41398-018-0337-x.
APA：
Zhao, Lijuan,Chang, Hong,Zhou, Dong-Sheng,Cai, Jun,Fan, Weixing...&Li, Ming.(2018).Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population.TRANSLATIONAL PSYCHIATRY,8,
MLA：
Zhao, Lijuan,et al."Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population".TRANSLATIONAL PSYCHIATRY 8.(2018)
医学