Linkage disequilibrium mapping of the chromosome 6q21-22.31 bipolar I disorder susceptibility locus.
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.
Fan
Jinbo
J
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
Ionita-Laza
Iuliana
I
McQueen
Matthew B
MB
Devlin
Bernie
B
Purcell
Shaun
S
Faraone
Stephen V
SV
Allen
Michael H
MH
Bowden
Charles L
CL
Calabrese
Joseph R
JR
Fossey
Mark D
MD
Friedman
Edward S
ES
Gyulai
Laszlo
L
Hauser
Peter
P
Ketter
Terence B
TB
Marangell
Lauren B
LB
Miklowitz
David J
DJ
Nierenberg
Andrew A
AA
Patel
Jayendra K
JK
Sachs
Gary S
GS
Thase
Michael E
ME
Molay
Francine B
FB
Escamilla
Michael A
MA
Nimgaonkar
Vishwajit L
VL
Sklar
Pamela
P
Laird
Nan M
NM
Smoller
Jordan W
JW
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