OBJECTIVES: 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. CONCLUSION: PDLIM5 may have a minor effect on susceptibility to BP in Caucasians. The findings in Japanese need further confirmation in larger independent samples.
OBJECTIVES: 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. CONCLUSION:PDLIM5 may have a minor effect on susceptibility to BP in Caucasians. The findings in Japanese need further confirmation in larger independent samples.
Authors: B J Mowry; K R Ewen; D J Nancarrow; D P Lennon; D A Nertney; H L Jones; M S O'Brien; C E Thornley; M K Walters; R R Crowe; J M Silverman; J Endicott; L Sharpe; N K Hayward; M M Gladis; S J Foote; D F Levinson Journal: Am J Med Genet Date: 2000-12-04
Authors: Christopher S Carlson; Michael A Eberle; Mark J Rieder; Qian Yi; Leonid Kruglyak; Deborah A Nickerson Journal: Am J Hum Genet Date: 2003-12-15 Impact factor: 11.025
Authors: Stefano Romeo; Len A Pennacchio; Yunxin Fu; Eric Boerwinkle; Anne Tybjaerg-Hansen; Helen H Hobbs; Jonathan C Cohen Journal: Nat Genet Date: 2007-02-25 Impact factor: 38.330