TY - JOUR
T1 - Family-based SNP association study on 8q24 in bipolar disorder
AU - Zandi, Peter P.
AU - Zöllner, Sebastian
AU - Avramopoulos, Dimitrios
AU - Willour, Virginia L.
AU - Chen, Yi
AU - Qin, Zhaohui S.
AU - Burmeister, Margit
AU - Miao, Kuangyi
AU - Gopalakrishnan, Shyam
AU - McEachin, Richard
AU - Potash, James B.
AU - DePaulo, J. Raymond
AU - McInnis, Melvin G.
PY - 2008/7/5
Y1 - 2008/7/5
N2 - 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.
AB - 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.
KW - Bipolar disorder
KW - Chromosome 8q24
KW - Dominant-dominant model
KW - Genetic association
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U2 - 10.1002/ajmg.b.30651
DO - 10.1002/ajmg.b.30651
M3 - Article
C2 - 18163389
AN - SCOPUS:46949096351
SN - 1552-4841
VL - 147
SP - 612
EP - 618
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 5
ER -