Association analysis of the chromosome 4p15-p16 candidate region for bipolar disorder and schizophrenia.

Several independent linkage studies have identified chromosome 4p15-p16 as a putative region of susceptibility for bipolar disorder (BP), schizophrenia (SCZ) and related phenotypes. Previously, we identified two subregions (B and D) of the 4p15-p16 region that are shared by three of four 4p-linked families examined. Here, we describe a large-scale association analysis of regions B and D (3.8 and 4.5 Mb, respectively). We selected 408 haplotype-tagging single nucleotide polymorphisms (SNPs) on a block-by-block basis from the International HapMap project and tested them in 368 BP, 386 SCZ and 458 control individuals. Nominal significance thresholds were determined using principal component analysis as implemented in the program SNPSpD. In region B, overlapping SNPs and haplotypes met the region-wide threshold (PBP and/or SCZ (region-wide threshold, PP(gp)KIAA0746 and PPARGC1A, mapped nearby. There were also nine other clusters within regions B and D with nominally significant haplotypes, but only at the individual haplotype level. KIAA0746, PPARGC1A, GPR125, CCKAR and DKFZp761B107 overlapped with these regions. This study has identified significant associations between BP and SCZ within the chromosome 4p linkage region, resulting in candidate regions worthy of further investigation.

Citation

A Christoforou, S Le Hellard, P A Thomson, S W Morris, A Tenesa, B S Pickard, N R Wray, W J Muir, D H Blackwood, D J Porteous, K L Evans. Association analysis of the chromosome 4p15-p16 candidate region for bipolar disorder and schizophrenia. Molecular psychiatry. 2007 Nov;12(11):1011-25

Mesh Tags

PMID: 17457313

search → result