title: Family-based SNP association study on 8q24 in bipolar disorder.
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 x 10(-5)). However, there was consistent evidence at our threshold for the suggestive level (P < 7.00 x 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 x 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.
authors.affiliation: Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA. pzandi@jhsph.edu
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zandi
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zöllner
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Avramopoulos
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Willour
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhaohui S
authors.initials: ZS
authors.lastname: Qin
authors.forename: Margit
authors.initials: M
authors.lastname: Burmeister
authors.forename: Kuangyi
authors.initials: K
authors.lastname: Miao
authors.forename: Shyam
authors.initials: S
authors.lastname: Gopalakrishnan
authors.forename: Richard
authors.initials: R
authors.lastname: McEachin
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.forename: J Raymond
authors.initials: JR
authors.lastname: Depaulo
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
mesh_terms: D001714:Bipolar Disorder / Q000145:classification / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*