Author:
Li Ming,Luo Xiong-jian,Landén Mikael,Bergen Sarah E.,Hultman Christina M.,Li Xiao,Zhang Wen,Yao Yong-Gang,Zhang Chen,Liu Jiewei,Mattheisen Manuel,Cichon Sven,Mühleisen Thomas W.,Degenhardt Franziska A.,Nöthen Markus M.,Schulze Thomas G.,Grigoroiu-Serbanescu Maria,Li Hao,Fuller Chris K.,Chen Chunhui,Dong Qi,Chen Chuansheng,Jamain Stéphane,Leboyer Marion,Bellivier Frank,Etain Bruno,Kahn Jean-Pierre,Henry Chantal,Preisig Martin,Kutalik Zoltán,Castelao Enrique,Wright Adam,Mitchell Philip B.,Fullerton Janice M.,Schofield Peter R.,Montgomery Grant W.,Medland Sarah E.,Gordon Scott D.,Martin Nicholas G.,Rietschel Marcella,Liu Chunyu,Kleinman Joel E.,Hyde Thomas M.,Weinberger Daniel R.,Su Bing, ,
Abstract
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.
Publisher
Royal College of Psychiatrists
Subject
Psychiatry and Mental health