title: Linkage disequilibrium mapping of the chromosome 6q21-22.31 bipolar I disorder susceptibility locus.
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.
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Fan
authors.forename: Iuliana
authors.initials: I
authors.lastname: Ionita-Laza
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McQueen
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Michael H
authors.initials: MH
authors.lastname: Allen
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bowden
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fossey
authors.forename: Edward S
authors.initials: ES
authors.lastname: Friedman
authors.forename: Laszlo
authors.initials: L
authors.lastname: Gyulai
authors.forename: Peter
authors.initials: P
authors.lastname: Hauser
authors.forename: Terence B
authors.initials: TB
authors.lastname: Ketter
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Marangell
authors.forename: David J
authors.initials: DJ
authors.lastname: Miklowitz
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.forename: Jayendra K
authors.initials: JK
authors.lastname: Patel
authors.forename: Gary S
authors.initials: GS
authors.lastname: Sachs
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Francine B
authors.initials: FB
authors.lastname: Molay
authors.forename: Michael A
authors.initials: MA
authors.lastname: Escamilla
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide