Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample

Green, Elaine Karen, Hamshere, Marian L. ORCID: https://orcid.org/0000-0002-8990-0958, Forty, Elizabeth, Gordon-Smith, K., Fraser, Christine, Russell, Elen Elizabeth, Grozeva, Detelina Valentinova ORCID: https://orcid.org/0000-0003-3239-8415, Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Moran, J. L., Purcell, S., Sklar, P., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Jones, L. ORCID: https://orcid.org/0000-0001-5821-5889, Jones, Ian Richard ORCID: https://orcid.org/0000-0001-5821-5889 and Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610 2013. Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample. Molecular Psychiatry 18 (12) , pp. 1302-1307. 10.1038/mp.2012.142

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Abstract

We have conducted a genotyping study using a custom Illumina Infinium HD genotyping array, the ImmunoChip, in a new UK sample of 1218 bipolar disorder (BD) cases and 2913 controls that have not been used in any studies previously reported independently or in meta-analyses. The ImmunoChip was designed before the publication of the Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder Working Group (PGC-BD) meta-analysis data. As such 3106 single-nucleotide polymorphisms (SNPs) with a P-value <1 × 10−3 from the BD meta-analysis by Ferreira et al. were genotyped. We report support for two of the three most strongly associated chromosomal regions in the Ferreira study, CACNA1C (rs1006737, P=4.09 × 10−4) and 15q14 (rs2172835, P=0.043) but not ANK3 (rs10994336, P=0.912). We have combined our ImmunoChip data (569 quasi-independent SNPs from the 3016 SNPs genotyped) with the recently published PGC-BD meta-analysis data, using either the PGC-BD combined discovery and replication data where available or just the discovery data where the SNP was not typed in a replication sample in PGC-BD. Our data provide support for two regions, at ODZ4 and CACNA1C, with prior evidence for genome-wide significant (GWS) association in PGC-BD meta-analysis. In addition, the combined analysis shows two novel GWS associations. First, rs7296288 (P=8.97 × 10−9, odds ratio (OR)=0.9), an intergenic polymorphism on chromosome 12 located between RHEBL1 and DHH. Second, rs3818253 (P=3.88 × 10−8, OR=1.16), an intronic SNP on chromosome 20q11.2 in the gene TRPC4AP, which lies in a high linkage disequilibrium region along with the genes GSS and MYH7B.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Neuroscience and Mental Health Research Institute (NMHRI) Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	bipolar disorder; genome-wide significant association; immunoChip; PGC-BD; rs3818253; rs7296288
Additional Information:	Online publication date: 16 October 2012.
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	1359-4184
Last Modified:	09 Nov 2022 07:52
URI:	https://orca.cardiff.ac.uk/id/eprint/41473

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