Impact of Population Stratification on Family-Based Association in an Admixed Population.

T B Mersha,L J Martin,V Pilipenko,L Ding,L Kottyan,H He,X Zhang,B G Kurowski,D W Fardo,E S Alexander

doi:10.1155/2015/501617

Abstract

Population substructure is a well-known confounder in population-based case-control genetic studies, but its impact in family-based studies is unclear. We performed population substructure analysis using extended families of admixed population to evaluate power and Type I error in an association study framework. Our analysis shows that power was improved by 1.5% after principal components adjustment. Type I error was also reduced by 2.2% after adjusting for family substratification. The presence of population substructure was underscored by discriminant analysis, in which over 92% of individuals were correctly assigned to their actual family using only 100 principal components. This study demonstrates the importance of adjusting for population substructure in family-based studies of admixed populations.

Highlights

Complex diseases result from the interplay of multiple genetic and environmental factors
Our analysis shows that power was improved by 1.5% after principal components adjustment
Type I error was reduced by 2.2% after adjusting for family substratification

Summary

Introduction

Complex diseases result from the interplay of multiple genetic and environmental factors. Population-based designs sample individuals who are unrelated, as in casecontrol studies. Case-control design is based on allele or genotype frequencies comparison of unrelated affected and unaffected individuals in the population [1]. Case-control designs have practical advantages over family-based designs in sample recruitment and collecting DNA from unrelated cases and controls, family-based association studies have received much attention in the literature because of their robustness to population stratification and higher power to detect very rare variants with small effects compared to case-control studies. Most population stratifications occur when there are multiple races or ethnicities in case-control study design, significant population stratification can be identified even within an apparently homogeneous North American population of European ancestry [5]. Recent study found that individuals, who are identified as white, have about 3.5% nonEuropean ancestry [6]

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