Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance

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	Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance
	Li M[*]1,2; Luo XJ 3; Landen M 4,5; Bergen SE 4,6; Hultman CM 4; Li XY[1]3; Zhang W 3; Yao YG 3; Zhang C 7,8; Liu JW 1,9
刊名	BRITISH JOURNAL OF PSYCHIATRY
	2015
卷号	208 期号:2 页码:128-137
通讯作者	limingkiz@gmail.com ; sub@mail.kiz.ac.cn
英文摘要	BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10^-5). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10^-8). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
收录类别	SCI
资助信息	This work was supported by grants from the National 973 project of China (2011CBA00401), the National Natural Science Foundation of China (U1202225, 31130051, 31071101 and 31221003), the German Federal Ministry of Education and Research, the National Genome Research Network, Germany, the Integrated Genome Research Network MooDS, Germany (grant 01GS08144 to S.C. and M.M.N., grant 01GS08147 to M.R. and T.G.S.), the 111 Project (B07008) of the Ministry of Education of China, the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020000), the National Authority for Scientific Research, Bucharest, Romania (UEFISCDI – PN-II-89/2012) and Personal Genetics SRL, Bucharest, Romania.
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9447]
专题	昆明动物研究所_比较基因组学昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_遗传资源与进化国家重点实验室昆明动物研究所_重大疾病机理的遗传学昆明动物研究所_神经系统疾病昆明动物研究所_转化基因组
作者单位	1.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Yunnan, Peoples R China 2.Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA 3.Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China 4.Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden 5.Gothenburg Univ, Sect Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden 6.Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA 7.Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Schizophrenia Program, Shanghai 200030, Peoples R China 8.Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China 9.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming, Yunnan, Peoples R China 10.Aarhus Univ, Dept Biomed, Aarhus C, Denmark
推荐引用方式 GB/T 7714	Li M[*],Luo XJ,Landen M,et al. Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance[J]. BRITISH JOURNAL OF PSYCHIATRY,2015,208(2):128-137.
APA	Li M[].,Luo XJ.,Landen M.,Bergen SE.,Hultman CM.,...&Su B[].(2015).Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.BRITISH JOURNAL OF PSYCHIATRY,208(2),128-137.
MLA	Li M[*],et al."Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance".BRITISH JOURNAL OF PSYCHIATRY 208.2(2015):128-137.