Identifying rarer genetic variants for common complex diseases: diseased versus neutral discovery panels.

Annals of Human Genetics
Karen CurtinNicola J Camp

Abstract

The power of genetic association studies to identify disease susceptibility alleles fundamentally relies on the variants studied. The standard approach is to determine a set of tagging-SNPs (tSNPs) that capture the majority of genomic variation in regions of interest by exploiting local correlation structures. Typically, tSNPs are selected from neutral discovery panels - collections of individuals comprehensively genotyped across a region. We investigated the implications of discovery panel design on tSNP performance in association studies using realistically-simulated sequence data. We found that discovery panels of 24 sequenced 'neutral' individuals (similar to NIEHS or HapMap ENCODE data) were sufficient to select well-powered tSNPs to identify common susceptibility alleles. For less common alleles (0.01-0.05 frequency) we found neutral panels of this size inadequate, particularly if low-frequency variants were removed prior to tSNP selection; superior tSNPs were found using panels of diseased individuals. Only large neutral panels (200 individuals) matched diseased panel performance in selecting well-powered tSNPs to detect both common and rarer alleles. The 1000 Genomes Project initiative may provide larger neutral panels ...Continue Reading

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Citations

Aug 20, 2009·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Karen CurtinUNKNOWN Colorectal Cancer Study Group
Jan 1, 2009·Pharmacogenomics and Personalized Medicine·Wolfgang Hueber, William H Robinson
Jun 1, 2014·Genes·Christopher Ryan King, Dan L Nicolae
Nov 14, 2019·International Journal of Molecular Sciences·Antonio Simone LaganàDan C Martin

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