Chunk #21 — Limitations and misunderstandings of clinical, translational, and research applications of PRS — Pleiotropy, confounding, and causal inference
While causal inference with genetic data can be highly valuable, a notable caveat relates to collider bias. This describes the phenomenon in which conditioning on a common effect of exposure and outcome results in an over- or under-identification of genetic risk factors influencing disease outcome (42; 47; 48). A logical example arises from the fact that sex and autosomal variants both influence height but are intrinsically unrelated, as no autosomal variants determine sex. However, autosomal loci are spuriously associated with sex when modeled with SNPs and height covariates (i.e.: sex ~ SNP + height) (49).
