Fig. 1

Statistical power (i.e., the probability of detecting an association when it truly exists) to detect association between a genetic variant and infection susceptibility at the genome-wide significance level (5e−8) [18]. A 1:1 case-control study design was used for all parameter settings. Reported effect sizes are on the odds ratio (OR) scale, parameterized as log-additive for each additional protective allele. a Assuming perfect test accuracy and baseline infection susceptibility at 80% based on recent estimates [15], there is low statistical power to detect true associations when there is either low population-level exposure to SARS-CoV-2 or moderate genetic (protective) effect sizes (OR = 0.7). Detecting rare variants (MAF = 0.01) remains challenging even with a much larger protective effect size (OR = 0.2). b Reducing sensitivity for testing SARS-CoV-2 infection not only reduces statistical power but also negates gains that result from increasing population exposure. c Assuming 20% population exposure rate seen in the hardest-hit regions, baseline infection susceptibility, in the absence of the contributing protective genetic allele, can also severely impact power. Higher infection susceptibility (i.e., higher infectivity) can diminish any chance of detecting true signals with currently available sample sizes. Lower population exposure will further dampen statistical power as seen in a. MAF, minor allele frequency