Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening

Abstract Background Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance. Results We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity. Conclusion Our analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks

Additional file 3: Figure S1. of Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening

Plot of the first and second principal components obtained by Principal Component Analysis on 44 geographic groups (described in Additional file 2: Table S1) and 1142 AIMs. Each geographic group is shown as a point and is colored according to the continental group to which it belongs. The plot illustrates that the AIMs separate most continental groups well, but the Middle Eastern and Central Asian groups do not form distinct clusters. (PNG 49 kb

Additional file 2: of Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening

Supplementary tables. (XLSX 39181 kb