Family-based SNP association study on 8q24 in bipolar disorder Please cite this article as follows: Zandi PP, Zoellner S, Avramopoulos D, Willour VL, Chen Y, Qin ZS, Burmeister M, Miao K, Gopalakrishnan S, McEachin R, Potash JB, DePaulo JR Jr., McInnis MG. 2007. Family-Based SNP Association Study on 8q24 in Bipolar Disorder. Am J Med Genet Part B 147B:612–618.

Abstract

Previous linkage studies have identified chromosome 8q24 as a promising positional candidate region to search for bipolar disorder (BP) susceptibility genes. We, therefore, sought to identify BP susceptibility genes on chromosome 8q24 using a family-based association study of a dense panel of SNPs selected to tag the known common variation across the region of interest. A total of 1,458 SNPs across 16 Mb of 8q24 were examined in 3,512 subjects, 1,954 of whom were affected with BP, from 737 multiplex families. Single-locus tests were carried out with FBAT and Geno-PDT, and multi-locus test were carried out with HBAT and multi-locus Geno-PDT. None of the SNPs were associated with BP in the single-locus tests at a level that exceeded our threshold for study-wide significance ( P < 3.00 × 10 −5 ). However, there was consistent evidence at our threshold for the suggestive level ( P < 7.00 × 10 −4 ) from both the single locus and multi-locus tests of associations with SNPs in the genes ADCY8, ST3GAL1, and NSE2. Multi-locus analyses suggested joint effects between ADCY8 and ST3GAL1 ( P = 3.00 × 10 −4 ), with at least one copy of the “high risk” allele required at both genes for association with BP, consistent with a jointly dominant–dominant model of action. These findings with ADCY8 and ST3GAL1 warrant further investigation in order to confirm the observed associations and their functional significance for BP susceptibility. © 2007 Wiley-Liss, Inc.