Genome-wide association study of bipolar disorder in European American and African American individuals

E. N. Smith, C. S. Bloss, J. A. Badner, T. Barrett, P. L. Belmonte, W. Berrettini, W. Byerley, W. Coryell, D. Craig, H. J. Edenberg, E. Eskin, T. Foroud, E. Gershon, T. A. Greenwood, M. Hipolito, D. L. Koller, W. B. Lawson, C. Liu, F. Lohoff, M. G. McInnisF. J. McMahon, D. B. Mirel, S. S. Murray, C. Nievergelt, J. Nurnberger, E. A. Nwulia, J. Paschall, J. B. Potash, J. Rice, T. G. Schulze, W. Scheftner, C. Panganiban, N. Zaitlen, P. P. Zandi, S. Zöllner, N. J. Schork, J. R. Kelsoe

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Abstract

To identify bipolar disorder (BD) genetic susceptibility factors, we conducted two genome-wide association (GWA) studies: one involving a sample of individuals of European ancestry (EA; n1001 cases; n1033 controls), and one involving a sample of individuals of African ancestry (AA; n345 cases; n670 controls). For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence for association included rs5907577 in an intergenic region at Xq27.1 (P1.6 × 10 6) and rs10193871 in NAP5 at 2q21.2 (P9.8 × 10 6). For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P1.5 × 10 6) and rs2769605 in NTRK2 at 9q21.33 (P4.5 × 10 5). We also investigated whether we could provide support for three regions previously associated with BD, and we showed that the ANK3 region replicates in our sample, along with some support for C15Orf53; other evidence implicates BD candidate genes such as SLITRK2. We also tested the hypothesis that BD susceptibility variants exhibit genetic background-dependent effects. SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P1.4 × 10 6), rs4657247 in RGS5 at 1q23.3 (P4.1 × 10 6), and rs7078071 in BTBD16 at 10q26.13 (P4.5 × 10 6). This study is the first to conduct GWA of BD in individuals of AA and suggests that genetic variations that contribute to BD may vary as a function of ancestry.

Original languageEnglish (US)
Pages (from-to)755-763
Number of pages9
JournalMolecular Psychiatry
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2009

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Keywords

  • Allelic heterogeneity
  • ANK3
  • Bipolar Genome Study
  • GAIN
  • Genetic background

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Smith, E. N., Bloss, C. S., Badner, J. A., Barrett, T., Belmonte, P. L., Berrettini, W., Byerley, W., Coryell, W., Craig, D., Edenberg, H. J., Eskin, E., Foroud, T., Gershon, E., Greenwood, T. A., Hipolito, M., Koller, D. L., Lawson, W. B., Liu, C., Lohoff, F., ... Kelsoe, J. R. (2009). Genome-wide association study of bipolar disorder in European American and African American individuals. Molecular Psychiatry, 14(8), 755-763. https://doi.org/10.1038/mp.2009.43