Type

Journal Article

Authors

Bing Su
Margaret J. Wright
Nicholas G. Martin
Barbara Franke
D P Hibar
Alejandro Arias Vásquez
S. E. Medland
J. L. Stein
F. Bellivier
A Heinz
and 38 others

Subjects

Psychiatry

Topics
genetic markers natural selection bipolar disorder association genes society risk factors gene expression gene expression regulation single nucleotide polymorphisms major depressive disorder mdd neuroscience prefrontal cortex psychology odds ratio intermediate phenotype creb1

Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. (2014)

Abstract 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 × 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 × 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.
Collections Ireland -> National College Ireland -> Status = Published
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion
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Ireland -> National College of Ireland -> Type = Article
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion: Psychology
Ireland -> Trinity College Dublin -> Psychiatry
Ireland -> Trinity College Dublin -> School of Medicine
Ireland -> National College of Ireland -> Status = Published
Ireland -> National College of Ireland -> Subject = B Philosophy. Psychology. Religion
Ireland -> Trinity College Dublin -> Psychiatry (Scholarly Publications)
Ireland -> National College of Ireland -> Subject = B Philosophy. Psychology. Religion: Psychology
Ireland -> National College Ireland -> Type = Article
Ireland -> Trinity College Dublin -> RSS Feeds

Full list of authors on original publication

Bing Su, Margaret J. Wright, Nicholas G. Martin, Barbara Franke, D P Hibar, Alejandro Arias Vásquez, S. E. Medland, J. L. Stein, F. Bellivier, A Heinz and 38 others

Experts in our system

1
Barbara Franke
Trinity College Dublin
Total Publications: 12
 
2
Andreas Heinz
Trinity College Dublin
Total Publications: 55