PDLIM5 and susceptibility to bipolar disorder: a family-based association study and meta-analysis.
OBJECTIVE
The postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain and LIM (Lin-11, Isl-1, and Mec-3) domain 5 (PDLIM5) gene has been analyzed as a candidate gene for both schizophrenia and bipolar disorder (BP) in Japanese samples. We performed a family-based association study to test the hypothesis that variants in PDLIM5 increase susceptibility to BP in European-Americans and a meta-analysis to clarify whether there is a single marker consistently contributing to risk for BP.


METHODS
Five single nucleotide polymorphisms in the PDLIM5 gene were genotyped in 290 European-American BP families. Programs Sibling-Transmission/Disequilibrium Test (sib_tdt) and PDTPHASE were used for allelic and haplotypic association, respectively. We carried out a meta-analysis combing our family-based data and case-control data from two Japanese sample sets and from two genome-wide association (GWA) studies.


RESULTS
Our association analysis showed no single nucleotide polymorphism associated with BP. A rare haplotype consisted of rs10008257 and rs2433320 had nominal association (P=0.045), which failed to survive correction for multiple tests. The meta-analysis identified a significant allelic association at rs2433320 in all combined samples (excluding overlapped samples in GWA: overall odds ratio=0.897, 95% confidence interval: 0.838-0.961, adjusted P=0.012) and in all Caucasian samples (excluding overlapped samples in GWA: overall odds ratio=0.905, 95% confidence interval: 0.843-0.971, adjusted P=0.032), but not in the Japanese samples.


CONCLUSIONS
PDLIM5 may have a minor effect on susceptibility to BP in Caucasians. The findings in Japanese need further confirmation in larger independent samples.
Shi
Jiajun
J
Department of Psychiatry, The University of Chicago, Chicago, Illinois 60637, USA.
Badner
Judith A
JA
Liu
Chunyu
C
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D016001:Confidence Intervals; D005190:Family; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D060588:LIM Domain Proteins; D015810:Linkage Disequilibrium / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C512485:PDLIM5 protein, human