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Am J Med Genet B Neuropsychiatr Genet DOI:10.1002/ajmg.b.30942

Linkage disequilibrium mapping of the chromosome 6q21-22.31 bipolar I disorder susceptibility locus.

Publication TypeJournal Article
Year of Publication2010
AuthorsFan, J, Ionita-Laza, I, McQueen, MB, Devlin, B, Purcell, S, Faraone, SV, Allen, MH, Bowden, CL, Calabrese, JR, Fossey, MD, Friedman, ES, Gyulai, L, Hauser, P, Ketter, TB, Marangell, LB, Miklowitz, DJ, Nierenberg, AA, Patel, JK, Sachs, GS, Thase, ME, Molay, FB, Escamilla, MA, Nimgaonkar, VL, Sklar, P, Laird, NM, Smoller, JW
JournalAm J Med Genet B Neuropsychiatr Genet
Volume153B
Issue1
Pages29-37
Date Published2010 Jan 05
ISSN1552-485X
KeywordsBipolar Disorder, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 6, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide
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 x 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 larger samples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder.

URLhttp://dx.doi.org/10.1002/ajmg.b.30942
DOI10.1002/ajmg.b.30942
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/19308960?dopt=Abstract

Alternate JournalAm. J. Med. Genet. B Neuropsychiatr. Genet.
PubMed ID19308960
PubMed Central IDPMC4067321
Grant ListR01 MH061675 / MH / NIMH NIH HHS / United States
MH061675 / MH / NIMH NIH HHS / United States
R01 MH059556 / MH / NIMH NIH HHS / United States
U01, MH060879 / MH / NIMH NIH HHS / United States
MH60870 / MH / NIMH NIH HHS / United States
MH59586 / MH / NIMH NIH HHS / United States
R01MH59553 / 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
R01 MH059567 / MH / NIMH NIH HHS / United States
R01 MH059545 / MH / NIMH NIH HHS / United States
R01MH59533 / 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
R01 MH059534 / MH / NIMH NIH HHS / United States
R01 MH059571 / MH / NIMH NIH HHS / United States
R01 MH059565 / MH / NIMH NIH HHS / United States
MH63420 / 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
MH059588 / MH / NIMH NIH HHS / United States
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
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
R01 MH063445 / MH / NIMH NIH HHS / United States
MH063445 / 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