A Cautionary Note on the Effects of Population Stratification Under an Extreme Phenotype Sampling Design.

ABSTRACT: Extreme phenotype sampling (EPS) is a popular study design used to reduce genotyping or sequencing costs. Assuming continuous phenotype data are available on a large cohort, EPS involves genotyping or sequencing only those individuals with extreme phenotypic values. Although this design has been shown to have high power to detect genetic effects even at smaller sample sizes, little attention has been paid to the effects of confounding variables, and in particular population stratification. Using extensive simulations, we demonstrate that the false positive rate under the EPS design is greatly inflated relative to a random sample of equal size or a "case-control"-like design where the cases are from one phenotypic extreme and the controls randomly sampled. The inflated false positive rate i

SUBMITTER: Panarella M 

PROVIDER: S-EPMC6509877 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature