Figure 2.

Enrichment for cases or controls produces spurious associations. We applied our analytical formula to compute the effect size estimate of a SNP (G) on a continuous risk factor (X) in the abovementioned liability scale model setting with the true genetic effect on the risk factor ($\gamma$) being zero. Enrichment for cases or controls produces spurious evidence of association between disease risk alleles and a risk factor correlated with the disease (equivalent to 2.5 OR per SD) in (A) a scenario where a risk allele (MAF 30%) increases risk with an effect equivalent to an OR of 1.4 (similar to the TCF7L2 type 2 diabetes scenario 10) in two models: unadjusted for disease status (solid curve) and adjusted for disease status (dashed curve). (Dash-)dotted lines represent 95% confidence interval (CI) around the effect estimate assuming a population of 100 000 individuals. (B) displays the same curves, but for a SNP with a rare protective allele (MAF 2%) that reduces risk of disease with an effect equivalent to an OR of 0.5 (similar to the CCND2 type 2 diabetes scenario 9). Vertical dashed line at 0.05 indicates the true general population disease prevalence.