Family-based SNP association study on 8q24 in bipolar disorder.
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.
Zandi
Peter P
PP
Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA. pzandi@jhsph.edu
Zöllner
Sebastian
S
Avramopoulos
Dimitrios
D
Willour
Virginia L
VL
Chen
Yi
Y
Qin
Zhaohui S
ZS
Burmeister
Margit
M
Miao
Kuangyi
K
Gopalakrishnan
Shyam
S
McEachin
Richard
R
Potash
James B
JB
Depaulo
J Raymond
JR
McInnis
Melvin G
MG
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*