A unifying framework for rare variant association testing in family-based designs, including higher criticism approaches, SKATs, and burden tests.

ABSTRACT: Analysis of rare variants in family-based studies remains a challenge. Transmission-based approaches provide robustness against population stratification, but the evaluation of the significance of test statistics based on asymptotic theory can be imprecise. In addition, power will depend heavily on the choice of the test statistic and on the underlying genetic architecture of the locus, which will be generally unknown. In our proposed framework, we utilize the FBAT haplotype algorithm to obtain the conditional offspring genotype distribution under the null hypothesis given the sufficient statistic. Based on this conditional offspring genotype distribution, the significance of virtually any association test statistic can be evaluated based on simulations or exact computations, without the n

SUBMITTER: Hecker J 

PROVIDER: S-EPMC8016468 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature