Inferring rare disease risk variants based on exact probabilities of sharing by multiple affected relatives.

ABSTRACT:

Motivation

Family-based designs are regaining popularity for genomic sequencing studies because they provide a way to test cosegregation with disease of variants that are too rare in the population to be tested individually in a conventional case-control study.

Results

Where only a few affected subjects per family are sequenced, the probability that any variant would be shared by all affected relatives-given it occurred in any one family member-provides evidence against the null hypothesis of a complete absence of linkage and association. A P-value can be obtained as the sum of the probabilities of sharing events as (or more) extreme in one or more families. We generalize an existing closed-form expression for exact sharing probabilities to more than two relatives per family

SUBMITTER: Bureau A 

PROVIDER: S-EPMC4103601 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature