BackgroundCurrent 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.ResultsWe 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (10.1186/s12863-017-0570-y) contains supplementary material, which is available to authorized users.

Background: Current professional society guidelines recommend genetic carrier screening be

often utilizing the standard ACOG prenatal genetic history form. This information was then compared to that discovered in the pre-GC intake form and through in-person GC. Missed genetic information was defined as information that was discovered on the pre-GC form or in-person GC that was not present on the initial genetic screening document from the obstetric provider. Missing genetic information that that lead to a change in clinical care, either through additional serum testing, imaging or invasive testing was considered significant. Statistical significance was assessed using Chi-squared testing with p<0.05 identifying significance. RESULTS: 299 patients underwent GC. 57.5% of patients were referred from private providers, 28.1% from academic faculty practice & 14.4% from a federally funded clinic. Missed genetic information was discovered in 171/299 (57.2%) of patients in the GC process. Of these 171 patients, 28.7% were revealed in the pre-GC form and 52.6% in the in-person GC. Of the 171 patients who had new genetic information discovered, 73 (42.7%) were significant. There was no statistical difference in race or referring office setting in the occurrence of new information found. The pre-GC intake form was found to be more likely than the in-person GC to find clinically significant missed genetic history (OR¼1.55; p¼0.037). CONCLUSION: In our population, genetic history obtained in the general obstetrician's office, regardless of practice type, missed over half of patient's genetic information with approximately 40% leading to a change in clinical care. Developing a genetic intake form similar to our pre-GC form may decrease missed genetic information in the general obstetrician's office.

We successfully validated our platform with two biorepositories, demonstrating high sensitivity and specificity. The 1000 Genomes Project samples provided both positive and negative validation for mutations in genes not available through other biorepositories, expanding the depth of validated variants. We recommend including samples from the 1000 Genomes Project in the validation of future multiplex testing platforms.Genet Med advance online publication 30 July 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.101.

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