Gene Expression and Genetic Variation Data Implicate PCLO in Bipolar Disorder

被引：49

作者：

Choi, Kwang H. ^{[1
,2
]}

Higgs, Brandon W. ^{[4
]}

Wendland, Jens R. ^{[3
]}

Song, Jonathan ^{[2
]}

McMahon, Francis J. ^{[3
]}

Webster, Maree J. ^{[2
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA

[2] Uniformed Serv Univ Hlth Sci, Stanley Lab Brain Res, Bethesda, MD 20814 USA

[3] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[4] Elashoff Consulting, Redwood City, CA USA

来源：

BIOLOGICAL PSYCHIATRY | 2011年 / 69卷 / 04期

关键词：

Allelic expression; expression quantitative trait loci (eQTL); genetic variants; functional genomics; risk factors; GENOME-WIDE ASSOCIATION; FALSE DISCOVERY RATE; METAANALYSIS; SNPS; DEPRESSION; SUPPORTS; LINKAGE; LOCUS;

D O I：

10.1016/j.biopsych.2010.09.042

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Background: Genetic variation may contribute to differential gene expression in the brain of individuals with psychiatric disorders. To test this hypothesis, we identified genes that were differentially expressed in individuals with bipolar disorder, along with nearby single nucleotide polymorphisms (SNPs) that were associated with expression of the same genes. We then tested these SNPs for association with bipolar disorder in large case-control samples. Methods: We used the Stanley Genomics Database to extract gene expression and SNP microarray data from individuals with bipolar disorder (n = 40) and unaffected controls (n = 43). We identified 367 genes that were differentially expressed in the prefrontal cortex of cases vs. controls (fold change > 1.3 and FDR q-value < .05) and 45 nearby SNPs that were associated with expression of those same genes (FDR q-value < .05). We tested these SNPs for association with bipolar disorder in a meta-analysis of genome-wide association studies (GWAS) including 4,936 cases and 6,654 healthy controls. Results: We identified 45 SNPs that were associated with expression of differentially expressed genes, including HBS1L (15 SNPs), HLA-DPB1 (15 SNPs), AMFR (8 SNPs), PCLO (2 SNPs) and WDR41 (2 SNPs). Of these, one SNP (rs13438494), in an intron of the piccolo (PCLO) gene, was significantly associated with bipolar disorder (FDR adjusted p < .05) in the meta-analysis of GWAS. Conclusions: These results support the previous findings implicating PCLO in mood disorders and demonstrate the utility of combining gene expression and genetic variation data to improve our understanding of the genetic contribution to bipolar disorder.

引用

页码：353 / 359

页数：7

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