Association study of Wnt signaling pathway genes in bipolar disorder

Abstract

Context: The Wnt signaling pathways promote cell growth and are best known for their role in embryogenesis and cancer. Several lines of evidence suggest that these pathways might also be involved in bipolar disorder. Objective: To test for an association between candidate genes in the Wnt signaling pathways and disease susceptibility in a family-based bipolar disorder study. Design: Two hundred twenty-seven tagging single-nucleotide polymorphisms (SNPs) from 34 genes were successfully genotyped. Initial results led us to focus on the gene PPARD, in which we genotyped an additional 13 SNPs for follow-up. Setting: Nine academic medical centers in the United States. Participants: Five hundred fifty-four offspring with bipolar disorder and their parents from 317 families. Main Outcome Measures: Family-based association using FBAT and HBAT (http://www.biostat.harvard.edu/∼fbat/default.html; Harvard School of Public Health, Boston, Massachusetts). Exploratory analyses testing for interactions of PPARD SNPs with clinical covariates and with other Wnt genes were conducted with GENASSOC (Stata Corp, College Station, Texas). Results: In the initial analysis, the most significantly associated SNP was rs2267665 in PPARD (nominal P