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Family-based SNP Association Study on 8q24 in Bipolar Disorder
Journal article   Peer reviewed

Family-based SNP Association Study on 8q24 in Bipolar Disorder

Peter P Zandi, Sebastian Zoellner, Dimitrios Avramopoulos, Virginia L Willour, Yi Chen, Zhaohui S Qin, Margit Burmeister, Kuangyi Miao, Shyam Gopalakrishnan, Richard McEachin, …
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.147B(5), pp.612-618
07/05/2008
DOI: 10.1002/ajmg.b.30651
PMCID: PMC2700285
PMID: 18163389
url
https://hdl.handle.net/2027.42/60231View
Open Access

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.

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