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

We previously reported genomewide significant evidence for linkage between chromosome 6q and bipolar I disorder BPI by performing a metaanalysis of original genotype data from 11 genome scan linkage studies. We now present followup 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 familybased 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 SLC22A16and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNPwise and genebased 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. © 2009 WileyLiss, Inc.