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

TitleLinkage 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
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Volume153B
Issue1
Pagination29-37
Date Published2010 Jan 5
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.

Alternate JournalAm. J. Med. Genet. B Neuropsychiatr. Genet.