Fig. 1

CPMC process for risk reporting. A, Candidate genetic variant/health condition associations are identified by searches of public databases such as PubMed, HuGENet,¹⁹ and the National Human Genome Research Institute GWAS catalog.²⁰ The minimum inclusion criteria for candidate genetic variants is a documented association with the disease in a moderately sized study (defined as having 500 or more subjects) with replication in one or more cohorts of the same race, either replicated within a single peer-reviewed publication or published in a separate study. For each health condition, SNPs are prioritized according to the greatest amount of supportive evidence (according to the variant selection hierarchy). SNPs with multiple independent published reports and preferably additional supportive meta-analysis are preferentially chosen. If more than one equally well-supported risk variant is available for a given health condition, the SNP with the largest OR for disease is selected. If the OR estimates do not differ for more than one genetic variant, then an arbitrary selection of the risk variant is made. Currently, only genetic variants contained on the Affymetrix 6.0 platform have been considered for inclusion in the CPMC. Additional variants not included on this platform will be considered in the future. B, Proposed genetic variant/health condition associations are assessed by the independent advisory board, the ICOB. Only genetic variant associations considered valid and health conditions deemed to be potentially actionable are approved for CPMC risk reporting. C, Publications used for risk reporting are selected based on the strength of the study design and an assessment of study quality. D, RR values are either reported directly from the selected paper (cohort studies) or estimated from the reported OR (case-control studies). When the OR overestimates the estimated RR by 10% or less, the OR is reported as an estimate of RR.