Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility

CORC > 昆明动物研究所 > 昆明动物研究所 > 遗传资源与进化国家重点实验室 > 比较基因组学

	Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility
	Li M 1,2,3; Luo XJ 3; Su B[*]1; Nothen, MM 18,19,20; Rietschel M 4,5; Lewis CM 6; Mattheisen M 7,8
刊名	MOLECULAR PSYCHIATRY
	2014
卷号	19 期号:4 页码:452-461
关键词	association bipolar disorder CREB1 gene expression intermediate phenotype natural selection
通讯作者	sub@mail.kiz.ac.cn
英文摘要	Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P = 6.32 x 10(-5), odds ratio (OR) = 1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P < 0.005) and the prefrontal cortex (P < 1.0 x 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.
收录类别	SCI
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/10804]
专题	昆明动物研究所_比较基因组学昆明动物研究所_遗传资源与进化国家重点实验室昆明动物研究所_转化基因组
作者单位	1.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R Chin 3.Univ Rochester, Flaum Eye Inst, Rochester, NY USA 4.Hop H Mondor A Chenevier, AP HP, Creteil, France 5.Univ Paris Est, Fac Med, Creteil, France 6.Gothenburg Univ, Sahlgrenska Acad, Sect Psychiat & Neurochem, Gothenburg, Sweden 7.Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden 8.Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Imaging Genet Ctr,Lab Neuro Imaging, Los Angeles, CA 90095 USA 9.Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany 10.Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany
推荐引用方式 GB/T 7714	Li M,Luo XJ,Su B[*],et al. Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility[J]. MOLECULAR PSYCHIATRY,2014,19(4):452-461.
APA	Li M.,Luo XJ.,Su B[*].,Nothen, MM.,Rietschel M.,...&Mattheisen M.(2014).Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.MOLECULAR PSYCHIATRY,19(4),452-461.
MLA	Li M,et al."Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility".MOLECULAR PSYCHIATRY 19.4(2014):452-461.