Ascertainment bias in the estimation of sibling genetic risk parameters

Abstract

The sibling recurrence risk, sibling relative risk, and locus-specific sibling relative risk are fundamental quantities in genetic epidemiologic research and are often estimated without accounting for the sampling scheme. For data generated under some genetic models, bias of estimates may be large if the sampling method is incorrectly modeled. In this paper, we explore the relationship between ascertainment of sibships and estimation and interpretation of genetic risk parameters. In particular, we observe that, although traditional definitions of these population parameters are consistent with each other, implied assumptions about ascertainment and the nature of ascertainment correction differ. In the absence of ascertainment correction, unbiased estimation of sibling recurrence risk and overall sibling relative risk requires single ascertainment, while unbiased estimation of locus-specific sibling relative risk requires complete ascertainment.