A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2

Figure 1

Performance of the case-control likelihood ratio method and odds ratio analysis in providing at least strong ACMG/AMP evidence in favor of pathogenicity () using simulated datasets. Power equals the probability of reaching at least strong pathogenic ACMG/AMP evidence. Genotype data simulations were carried out for causal variants conferring disease relative risk between 2 and 10. We performed 10,000 simulations for each case scenario. Results represent simulated case-control data for 20,000 (a–c), 30,000 (d–f), or 50,000 (g–i) breast cancer cases and controls and minor allele frequency of 0.00003 (a, d, g), 0.00005 (b, e, h), or 0.0001 (c, f, i). ccLR: case-control likelihood ratio; MAF: minor allele frequency; : sample size.

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