The Relation Between Inflation in Type-I and Type-II Error Rate and Population Divergence in Genome-Wide Association Analysis of Multi-Ethnic Populations.

Derks EM, Zwinderman AH, Gamazon ER
Behav Genet. 2017 47 (3): 360-368

PMID: 28185111 · PMCID: PMC5403879 · DOI:10.1007/s10519-017-9837-3

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 (F) 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 F between the ancestral European and African populations. Type-II error rate was investigated for a SNP characterized by a high value of F. 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.

MeSH Terms (4)

Genetics, Population Genome-Wide Association Study Humans Polymorphism, Single Nucleotide

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