Interpreting polygenic score effects in sibling analysis

• DOI: 10.1371/journal.pone.0282212
• Publication Date: 2024-02-15T18:28:07Z
• Authors: Jason Fletcher; Yuchang Wu; Tianchang Li; Qiongshi Lu
• Keywords: Nature versus nurture; Genetic Analysis; Additive genetic effects

Researchers often claim that sibling analysis can be used to separate causal genetic effects from the assortment of biases contaminate most downstream studies (e.g. polygenic score predictors). Indeed, typical results show large (>50%) attenuations in associations between scores and phenotypes compared non-sibling analysis, consistent with researchers’ expectations about bias reduction. This paper explores these by using family (quad) data simulations include indirect effect processes evaluates ability uncover direct scores. We find general, fail effects; indeed, models have both upward downward are difficult sign data. When nurture exist, creates “measurement error” attenuates phenotypes. As correlation changes, this increase or decrease. Our findings suggest interpreting aimed at uncovering should treated caution.