期刊
MOLECULAR PSYCHIATRY
卷 18, 期 12, 页码 1302-1307出版社
SPRINGERNATURE
DOI: 10.1038/mp.2012.142
关键词
bipolar disorder; genome-wide significant association; immunoChip; PGC-BD; rs3818253; rs7296288
资金
- Wellcome Trust [078901, 068545/Z/0, 076113/C/04/Z]
- Stanley Medical Research Institute via the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard
- Wellcome Trust under WTCCC
- Medical Research Council [G0000934]
- UK Blood Services collection of Common Controls (UKBS-CC collection)
- NIHR programme [RP-PG-0310-1002]
- Medical Research Council [G0000934, G0801418B] Funding Source: researchfish
- MRC [G0000934] Funding Source: UKRI
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 x 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 x 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 x 10(-9), odds ratio (OR) = 0.9), an intergenic polymorphism on chromosome 12 located between RHEBL1 and DHH. Second, rs3818253 (P = 3.88 x 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.
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