Modeling Heterogeneity in the Genetic Architecture of Ethnically Diverse Groups Using Random Effect Interaction Models

Genetics
Yogasudha C VeturiBrigitte Kühnel

Abstract

In humans, most genome-wide association studies have been conducted using data from Caucasians and many of the reported findings have not replicated in other populations. This lack of replication may be due to statistical issues (small sample sizes or confounding) or perhaps more fundamentally to differences in the genetic architecture of traits between ethnically diverse subpopulations. What aspects of the genetic architecture of traits vary between subpopulations and how can this be quantified? We consider studying effect heterogeneity using Bayesian random effect interaction models. The proposed methodology can be applied using shrinkage and variable selection methods, and produces useful information about effect heterogeneity in the form of whole-genome summaries (e.g., the proportions of variance of a complex trait explained by a set of SNPs and the average correlation of effects) as well as SNP-specific attributes. Using simulations, we show that the proposed methodology yields (nearly) unbiased estimates when the sample size is not too small relative to the number of SNPs used. Subsequently, we used the methodology for the analyses of four complex human traits (standing height, high-density lipoprotein, low-density lipop...Continue Reading

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Citations

Mar 22, 2020·Genetics·Scott A FunkhouserGustavo de Los Campos
Jan 14, 2020·The Journal of Clinical Investigation·Eugene MelamudGarret A FitzGerald
Sep 4, 2020·G3 : Genes - Genomes - Genetics·Bárbara D Bitarello, Iain Mathieson
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Jul 29, 2021·Translational Vision Science & Technology·Carla LancaSeang-Mei Saw
Aug 1, 2021·American Journal of Human Genetics·Iain Mathieson

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