Finding the Sources of Missing Heritability within Rare Variants Through Simulation.

Finding the Sources of Missing Heritability within Rare Variants Through Simulation. Bioinform Biol Insights. 2017;11:1177932217735096 Authors: Bandyopadhyay B, Chanda V, Wang Y Abstract Thousands of genome-wide association studies (GWAS) have been conducted to identify the genetic variants associated with complex disorders. However, only a small proportion of phenotypic variances can be explained by the reported variants. Moreover, many GWAS failed to identify genetic variants associated with disorders displaying hereditary features. The "missing heritability" problem can be partly explained by rare variants. We simulated a causality scenario that gestational ages, a quantitative trait that can distinguish preterm (<37 weeks) and term births, were significantly correlated with the rare variant aggregations at 1000 single-nucleotide polymorphism loci. These 1000 simulated causal rare variants were embedded into randomly selected subsets of 9642 promoter regions from the 1000 Genomes Project genotypic data according to different proportions of causal rare variants within the embedded promoters. Through analysis of the correlations between rare variant aggregations and gestational ages, we found that the embedded promoters as a whole showed weaker genetic association when the proportion of causal rare variants decreased, and no individual embedded promoters showed genetic association when the proportion of causal rare variants was...
Source: Bioinformatics and Biology Insights - Category: Bioinformatics Authors: Tags: Bioinform Biol Insights Source Type: research