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Chunk #62 — Materials and Methods — Identifying confounders on gene association scores

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Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits.
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The potential confounding effects of six gene properties on the most significant SNP p-value, for all genes g were examined using 1,000 DGI study permutations, described below. The gene features tested include: (1) Physical gene size for gene g, dg, defined as the distance in kilobase (kb) units between the most extreme transcript start and end sites of all isoforms of a given gene (including introns), plus an added distance. For the extended boundaries of −110kb/+40kb used for the mitochondrial and lipid analyses, 150 kb were added, and for the ±50 kb boundaries used for method development purposes, 100 kb were added; (2) Number of genotyped and imputed (if available) SNPs per kb for each gene g, ng; (3) Estimated number of independent SNPs (that are in approximate linkage equilibrium with each other) per kb for each gene g, ug. This was calculated using the –indep option in PLINK that prunes SNPs based on the variance inflation factor, VIF (http://pngu.mgh.harvard.edu/~purcell/plink/summary.shtml#prune; default parameters were used). The genotypes of the CEU population from HapMap version 19 were used, since the GWA samples