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Mol Psychiatry DOI:10.1038/sj.mp.4002151

Whole-genome association study of bipolar disorder.

Publication TypeJournal Article
Year of Publication2008
AuthorsSklar, P, Smoller, JW, Fan, J, Ferreira, MAR, Perlis, RH, Chambert, K, Nimgaonkar, VL, McQueen, MB, Faraone, SV, Kirby, A, de Bakker, PIW, Ogdie, MN, Thase, ME, Sachs, GS, Todd-Brown, K, Gabriel, SB, Sougnez, C, Gates, C, Blumenstiel, B, DeFelice, M, Ardlie, KG, Franklin, J, Muir, WJ, McGhee, KA, MacIntyre, DJ, McLean, A, VanBeck, M, McQuillin, A, Bass, NJ, Robinson, M, Lawrence, J, Anjorin, A, Curtis, D, Scolnick, EM, Daly, MJ, Blackwood, DH, Gurling, HM, Purcell, SM
JournalMol Psychiatry
Volume13
Issue6
Pages558-69
Date Published2008 Jun
ISSN1476-5578
KeywordsAntigens, Neoplasm, Bipolar Disorder, Chromosome Mapping, DNA, Gene Frequency, Genetic Markers, Genome, Human, Genotype, Humans, Medical History Taking, Membrane Glycoproteins, Myosin Heavy Chains, Myosin Type V, Patient Selection, Polymorphism, Single Nucleotide, Receptor, Epidermal Growth Factor, Reference Values, Tetraspanins
Abstract

We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

DOI10.1038/sj.mp.4002151
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/18317468?dopt=Abstract

Alternate JournalMol. Psychiatry
PubMed ID18317468
PubMed Central IDPMC3777816
Grant ListR01 MH061675 / MH / NIMH NIH HHS / United States
MH061675 / MH / NIMH NIH HHS / United States
R01 MH059556 / MH / NIMH NIH HHS / United States
MH60870 / MH / NIMH NIH HHS / United States
MH59586 / MH / NIMH NIH HHS / United States
RC2 MH089905 / MH / NIMH NIH HHS / United States
R01 MH059535 / MH / NIMH NIH HHS / United States
R01 MH59545 / MH / NIMH NIH HHS / United States
R01 HD060726 / HD / NICHD NIH HHS / United States
MH059571 / MH / NIMH NIH HHS / United States
R01 MH059567 / MH / NIMH NIH HHS / United States
R01 MH59533 / MH / NIMH NIH HHS / United States
R01 MH059545 / MH / NIMH NIH HHS / United States
MH067257 / MH / NIMH NIH HHS / United States
R01 MH062137 / MH / NIMH NIH HHS / United States
R01 MH059548 / MH / NIMH NIH HHS / United States
R01 MH067257 / MH / NIMH NIH HHS / United States
R01 MH060870 / MH / NIMH NIH HHS / United States
MH062137 / MH / NIMH NIH HHS / United States
R01 MH059534 / MH / NIMH NIH HHS / United States
R01 MH059571 / MH / NIMH NIH HHS / United States
R01 MH059565 / MH / NIMH NIH HHS / United States
/ / Intramural NIH HHS / United States
R01 MH59535 / MH / NIMH NIH HHS / United States
R01 MH59553 / MH / NIMH NIH HHS / United States
MH63420 / MH / NIMH NIH HHS / United States
R01 MH60068 / MH / NIMH NIH HHS / United States
R01 MH059587 / MH / NIMH NIH HHS / United States
R01 MH059533 / MH / NIMH NIH HHS / United States
R01 MH067288 / MH / NIMH NIH HHS / United States
MH059565 / MH / NIMH NIH HHS / United States
R01 MH059586 / MH / NIMH NIH HHS / United States
G0500791 / / Medical Research Council / United Kingdom
MH059588 / MH / NIMH NIH HHS / United States
G9623693N / / Medical Research Council / United Kingdom
Z01 MH002810 / MH / NIMH NIH HHS / United States
R01 MH059566 / MH / NIMH NIH HHS / United States
R01 MH063420 / MH / NIMH NIH HHS / United States
R01 MH059588 / MH / NIMH NIH HHS / United States
R01 MH59567 / MH / NIMH NIH HHS / United States
N01MH80001 / MH / NIMH NIH HHS / United States
R01 MH059553 / MH / NIMH NIH HHS / United States
MH59566 / MH / NIMH NIH HHS / United States
MH067288 / MH / NIMH NIH HHS / United States
/ / Wellcome Trust / United Kingdom
R01 MH063445 / MH / NIMH NIH HHS / United States
MH063445 / MH / NIMH NIH HHS / United States
066717 / / Wellcome Trust / United Kingdom
U01 MH060879 / MH / NIMH NIH HHS / United States
R01 MH060879 / MH / NIMH NIH HHS / United States
MH59587 / MH / NIMH NIH HHS / United States
R01 MH060068 / MH / NIMH NIH HHS / United States