Dec 12, 2017

A robust and powerful two-step testing procedure for local ancestry adjusted allelic association analysis in admixed populations

Genetic Epidemiology
Qing DuanYun Li

Abstract

Genetic association studies in admixed populations allow us to gain deeper understanding of the genetic architecture of human diseases and traits. However, population stratification, complicated linkage disequilibrium (LD) patterns, and the complex interplay of allelic and ancestry effects on phenotypic traits pose challenges in such analyses. These issues may lead to detecting spurious associations and/or result in reduced statistical power. Fortunately, if handled appropriately, these same challenges provide unique opportunities for gene mapping. To address these challenges and to take these opportunities, we propose a robust and powerful two-step testing procedure Local Ancestry Adjusted Allelic (LAAA) association. In the first step, LAAA robustly captures associations due to allelic effect, ancestry effect, and interaction effect, allowing detection of effect heterogeneity across ancestral populations. In the second step, LAAA identifies the source of association, namely allelic, ancestry, or the combination. By jointly modeling allele, local ancestry, and ancestry-specific allelic effects, LAAA is highly powerful in capturing the presence of interaction between ancestry and allele effect. We evaluated the validity and stat...Continue Reading

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Citations

Mentioned in this Paper

Genome-Wide Association Study
In Silico
Study
Patterns
Stratification
Candidate Disease Gene
Dysequilibrium Syndrome
Genetic Association Studies
Patient Care
Participant

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