Evidence for cis-acting regulation of ANK3 and CACNA1C gene expression

Bipolar Disorders
Emma M QuinnDerek W Morris

Abstract

Genome-wide association studies (GWAS) have identified Ankyrin-G (ANK3) and the alpha-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. We have done this by testing for allelic expression imbalance (AEI) to identify cis-acting regulatory polymorphisms. 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. These data indicate that there is genetic variation local to both genes affecting their ex...Continue Reading

References

Nov 5, 2002·Nature Reviews. Genetics·Pak ShamMichael Owen
May 3, 2003·Human Genetics·Nicholas J BrayMichael C O'Donovan
May 14, 2003·Archives of General Psychiatry·Peter McGuffinAlastair Cardno
Jun 13, 2003·American Journal of Human Genetics·Nicholas J BrayMichael C O'Donovan
Oct 7, 2004·The American Journal of Psychiatry·Tuula KieseppäJouko Lönnqvist
Sep 18, 2007·Nature Genetics·Anna L DixonWilliam O C Cookson
Nov 17, 2007·Science·Alexander GimelbrantAndrew Chess
Mar 13, 2008·Schizophrenia Bulletin·Nicholas J Bray
Apr 10, 2008·Nature Reviews. Genetics·Mark I McCarthyJoel N Hirschhorn
Aug 20, 2008·Nature Genetics·Manuel A R FerreiraUNKNOWN Wellcome Trust Case Control Consortium
Oct 15, 2008·Human Molecular Genetics·Alexandra C Nica, Emmanouil T Dermitzakis
Jan 16, 2009·Trends in Genetics : TIG·Nick Craddock, Pamela Sklar
Aug 1, 2009·Science·Antigone S DimasStylianos E Antonarakis

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Citations

Aug 26, 2011·Journal of Human Genetics·Tadafumi KatoKazuya Iwamoto
Aug 23, 2011·PloS One·Glenn A DoyleWade H Berrettini
Jun 28, 2011·BMC Psychiatry·Alejandro GellaMicha Gawlik
Jan 13, 2016·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Liang HuangMing Li
Jun 19, 2012·Progress in Neurobiology·Shambhu BhatTodd D Gould
Jan 31, 2013·Bipolar Disorders·Haiming ChenMelvin G McInnis
Oct 6, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Martin TesliOle A Andreassen
Jul 22, 2014·Bipolar Disorders·Zachary KaminskyJames B Potash
Feb 26, 2015·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Giuseppe DelvecchioSophia Frangou
Dec 24, 2013·Progress in Neuro-psychopharmacology & Biological Psychiatry·Chen ZhangYiru Fang
Apr 7, 2015·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Takuji UemuraJerry J Warsh
May 16, 2015·Neuroscience and Biobehavioral Reviews·Xiao OuBenjamin I Goldstein
Jun 7, 2015·European Archives of Psychiatry and Clinical Neuroscience·T M LancasterX Caseras
Dec 26, 2012·Trends in Molecular Medicine·Alasdair MacKenzieScott Davidson
Oct 27, 2017·Psychiatric Genetics·Yang Roby
Sep 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Shanshan ZhuChristopher A Ross
Sep 16, 2020·Interdisciplinary Sciences, Computational Life Sciences·Li QuHuaiqiu Zhu

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