Title: Improving power of genetic association studies by extreme phenotype sampling: a review and some new results,
Abstract: Extreme phenotype sampling is a selective genotyping design for genetic
association studies where only individuals with extreme values of a continuous
trait are genotyped for a set of genetic variants. Under financial or other
limitations, this design is assumed to improve the power to detect associations
between genetic variants and the trait, compared to randomly selecting the same
number of individuals for genotyping. Here we present extensions of likelihood
models that can be used for inference when the data are sampled according to
the extreme phenotype sampling design. Computational methods for parameter
estimation and hypothesis testing are provided. We consider methods for common
variant genetic effects and gene-environment interaction effects in linear
regression models with a normally distributed trait. We use simulated and real
data to show that extreme phenotype sampling can be powerful compared to random
sampling, but that this does not hold for all extreme sampling methods and
situations.