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

Christoforou, A., Le Hellard, S., Thomson, P. A., Morris, S. W., Tenesa, A., Pickard, B. S., Wray, N. R., Muir, W. J., Blackwood, D. H., Porteous, D. J. and Evans, K. L. (2007) Association analysis of the chromosome 4p15-p16 candidate region for bipolar disorder and schizophrenia. Molecular Psychiatry, 12 11: 1011-1025. doi:10.1038/

Author Christoforou, A.
Le Hellard, S.
Thomson, P. A.
Morris, S. W.
Tenesa, A.
Pickard, B. S.
Wray, N. R.
Muir, W. J.
Blackwood, D. H.
Porteous, D. J.
Evans, K. L.
Title Association analysis of the chromosome 4p15-p16 candidate region for bipolar disorder and schizophrenia
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
Publication date 2007
Sub-type Article (original research)
DOI 10.1038/
Open Access Status
Volume 12
Issue 11
Start page 1011
End page 1025
Total pages 15
Language eng
Subject 1312 Molecular Biology
2738 Psychiatry and Mental health
Abstract 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 (P≤0.0005) at the global and individual haplotype test level and clustered in two regions. In region D, no individual SNPs were nominally significant, but multiple global and individual haplotypes were associated with BP and/or SCZ (region-wide threshold, P≤0.0003). These overlapping haplotypes fell into two regions. Within each of these four clusters, at least one globally significant haplotype withstood permutation testing (Pgp≤0.05). Five predicted genes were found within these associated regions, while Known/RefSeq genes, including 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.
Keyword Association study
Bipolar disorder
Chromosome 4p
Haplotype analysis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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