title: The Relation Between Inflation in Type-I and Type-II Error Rate and Population Divergence in Genome-Wide Association Analysis of Multi-Ethnic Populations.
abstract: Population divergence impacts the degree of population stratification in Genome Wide Association Studies. We aim to: (i) investigate type-I error rate as a function of population divergence (FST) in multi-ethnic (admixed) populations; (ii) evaluate the statistical power and effect size estimates; and (iii) investigate the impact of population stratification on the results of gene-based analyses. Quantitative phenotypes were simulated. Type-I error rate was investigated for Single Nucleotide Polymorphisms (SNPs) with varying levels of FSTbetween the ancestral European and African populations. Type-II error rate was investigated for a SNP characterized by a high value of FST. In all tests, genomic MDS components were included to correct for population stratification. Type-I and type-II error rate was adequately controlled in a population that included two distinct ethnic populations but not in admixed samples. Statistical power was reduced in the admixed samples. Gene-based tests showed no residual inflation in type-I error rate.
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. e.m.derks@amc.uva.nl.|QIMR Berghofer, Translational Neurogenomics group, Brisbane, Australia. e.m.derks@amc.uva.nl.
authors.forename: E M
authors.initials: EM
authors.lastname: Derks
authors.affiliation: Department of Clinical Epidemiology and Bio-Statistics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. eric.gamazon@vanderbilt.edu.|Department of Clinical Epidemiology and Bio-Statistics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. eric.gamazon@vanderbilt.edu.|Division of Genetic Medicine, Department of Medicine, Vanderbilt University, 2215 Garland Avenue, Nashville, TN, USA. eric.gamazon@vanderbilt.edu.
authors.forename: E R
authors.initials: ER
authors.lastname: Gamazon
mesh_terms: D005828:Genetics, Population / Q000379:methods*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D020641:Polymorphism, Single Nucleotide
keywords: Admixture; FST; GWAS; Genome Wide Association; Population divergence; Population stratification; Principal components