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Activity Number: 306
Type: Contributed
Date/Time: Tuesday, August 2, 2016 : 8:30 AM to 10:20 AM
Sponsor: Biopharmaceutical Section
Abstract #321191 View Presentation
Title: Finding the 'Missing Heritability' in Combined Phase 2 and Subset Phase 3 Analyses
Author(s): Knut Wittkowski* and Benedetta Bigio
Companies: Rockefeller University and Rockefeller University
Keywords: non-parametric ; genetics ; GWAS ; Autism ; phase 2 ; phase 3
Abstract:

The clinical advances hoped for from genome-wide association studies (GWAS) have not yet materialized. Enlarging sample sizes to 10.000s limits the questions that can be addressed without guarding against non-functional SNPs differing between non-randomized populations. Combining a novel computational biostatistics approach with decision strategies fine-tuned to GWAS, we can now identify collections of related gene in groups of 100s of subjects only by (a) accounting for linkage disequilibrium (LD), varying dominance, and compound heterozygosity within a moving SNP window and (b) replacing the conventional fixed 7.5 level with a study-specific cut-off for GW significance that accounts for differences in MAF, the non-randomized nature of GWAS, and for tests in overlapping diplotypes being related. The approach was validated by confirming the known targets of epilepsy drugs in 185 childhood cases. Comparing non-verbal vs verbal cases in the two independent stages of the Autism Genome project suggested a drug to prevent permanent disruption of language development. Combined phase 2 data and subset phase 3 data can now be used to identify likely non-responders for subsequent studies.


Authors who are presenting talks have a * after their name.

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