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Evidence for cis ‐acting regulation of ANK3 and CACNA1C gene expression
Author(s) -
Quinn Emma M,
Hill Matthew,
Anney Richard,
Gill Michael,
Corvin Aiden P,
Morris Derek W
Publication year - 2010
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/j.1399-5618.2010.00817.x
Subject(s) - single nucleotide polymorphism , international hapmap project , genome wide association study , genetics , biology , expression quantitative trait loci , allele , genetic variation , gene , genetic association , snp , genotype
Quinn EM, Hill M, Anney R, Gill M, Corvin AP, Morris DW. Evidence for cis ‐acting regulation of ANK3 and CACNA1C gene expression.
Bipolar Disord 2010: 12: 440–445. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Genome‐wide association studies (GWAS) have identified Ankyrin‐G (ANK3) and the α‐1C subunit of the L‐type voltage‐gated calcium channel (CACNA1C) as susceptibility genes for bipolar disorder. Available biological information on these genes suggests a potential molecular mechanism involving ion channel dysfunction. The associated single nucleotide polymorphisms (SNPs) at ANK3 (rs10994336) and CACNA1C (rs1006737) are both intronic with no obvious impact on gene function. We investigated whether, instead of affecting protein function, these risk variants might impact on gene regulation affecting expression. Methods: We have done this by testing for allelic expression imbalance (AEI) to identify cis ‐acting regulatory polymorphisms. Results: We identified evidence of cis ‐acting variation at both loci in HapMap Caucasian Europeans from Utah (CEU) lymphoblastoid cell lines. There was considerable evidence of AEI at ANK3 with more than half of all heterozygous samples (21 out of 34) for marker SNP rs3750800 showing AEI and a small number of samples showing near monoallelic expression. The AEI at either gene could not be attributed to the GWAS‐associated SNPs. Conclusions: These data indicate that there is genetic variation local to both genes affecting their expression, but that this variation is not responsible for increasing risk of bipolar disorder.