Using family members to augment genetic case-control studies of a life-threatening disease.

ABSTRACT: Survival bias is difficult to detect and adjust for in case-control genetic association studies but can invalidate findings when only surviving cases are studied and survival is associated with the genetic variants under study. Here, we propose a design where one genotypes genetically informative family members (such as offspring, parents, and spouses) of deceased cases and incorporates that surrogate genetic information into a retrospective maximum likelihood analysis. We show that inclusion of genotype data from first-degree relatives permits unbiased estimation of genotype association parameters. We derive closed-form maximum likelihood estimates for association parameters under the widely used log-additive and dominant association models. Our proposed design not only permits a valid an

SUBMITTER: Chen L 

PROVIDER: S-EPMC4899219 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature