Biostatistics/SAGE Seminar: Pattern Mining of Epistatic Interactions in Genome-Wide Case-Control Association Studies

Presented by: University of Calgary
Category: Other Event
Price: $0
Date: December 9, 2016 – December 9, 2016
Address: 2500 University Drive NW, Calgary, Alberta T2N 1N4
Website: http://www.ucalgary.ca/

Dr. Qingrun Zhang of the Department of Biochemistry and Molecular Biology at the University of Calgary is giving the fall 2016 SAGE/Biostatistics Seminar entitled Pattern Mining of Epistatic Interactions in Genome-Wide Case-Control Association Studies. Summary of the talk: Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson’s chi-square test for the 2 x n contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term “glycosaminoglycan biosynthetic process” was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple evidences.

Location:

Mathematical Sciences 427

More information at http://www.ucalgary.ca/events/calendar/biostatisticssage-seminar-pattern-mining-epistatic-interactions-genome-wide-case-control


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2500 University Drive NW, Calgary, Alberta T2N 1N4
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