Linkage Disequilibrium Mapping of the Chromosome 6q21-22.31 Bipolar I Disorder Susceptibility Locus

Jinbo Fan, Iuliana Ionita-Laza, Matthew B. McQueen, Bernie Devlin, Shaun Purcell, Stephen V. Faraone, Michael H. Allen, Charles L. Bowden, Joseph R. Calabrese, Mark D. Fossey, Edward S. Friedman, Laszlo Gyulai, Peter Hauser, Terence B. Ketter, Lauren B. Marangell, David J. Miklowitz, Andrew A. Nierenberg, Jayendra K. Patel, Gary S. Sachs, Michael E. ThaseFrancine B. Molay, Michael A. Escamilla, Vishwajit L. Nimgaonkar, Pamela Sklar, Nan M. Laird, Jordan W. Smoller

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case-control sample (N=530 cases, 534 controls) and family-based sample (N=256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P=6.72×10 -5) was observed in the case-control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N=622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16, a carnitine transporter, implicating this gene as a novel candidate for BPI risk. Further studies in largersamples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number1
DOIs
StatePublished - Jan 1 2010

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Keywords

  • 6q
  • Association
  • Bipolar disorder
  • Genetic
  • SLC22A16

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Fan, J., Ionita-Laza, I., McQueen, M. B., Devlin, B., Purcell, S., Faraone, S. V., Allen, M. H., Bowden, C. L., Calabrese, J. R., Fossey, M. D., Friedman, E. S., Gyulai, L., Hauser, P., Ketter, T. B., Marangell, L. B., Miklowitz, D. J., Nierenberg, A. A., Patel, J. K., Sachs, G. S., ... Smoller, J. W. (2010). Linkage Disequilibrium Mapping of the Chromosome 6q21-22.31 Bipolar I Disorder Susceptibility Locus. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 153(1), 29-37. https://doi.org/10.1002/ajmg.b.30942