Genetic-ancestry analysis on >93,000 individuals undergoing expanded carrier screening reveals limitations of ethnicity-based medical guidelines

Kristjan E. Kaseniit, Imran S. Haque, James D. Goldberg, Lee P. Shulman, Dale Muzzey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose Despite strong association between genetic ancestry and carrier status, current carrier-screening guidelines recommend testing for a limited set of conditions based on a patient’s self-reported ethnicity, which conflates genetic and cultural factors. Materials and Methods For 93,419 individuals undergoing a 96-gene expanded carrier screen (ECS), correspondence was assessed among carrier status, self-reported ethnicity, and a dual-component genetic ancestry (e.g., 75% African/25% European) calculated from sequencing data. Results Self-reported ethnicity was an imperfect indicator of genetic ancestry, with 9% of individuals having >50% genetic ancestry from a lineage inconsistent with self-reported ethnicity. Self-reported ethnicity-based carrier-screening guidelines are incomplete, as several conditions not included in guidelines had similarly strong correlation between carrier rate and genetic ancestry as conditions included in screening guidelines. Limitations of self-reported ethnicity led to missed carriers in at-risk populations: for 10 ECS conditions, patients with intermediate genetic ancestry backgrounds—who did not self-report the associated ethnicity—had significantly elevated carrier risk. Finally, for seven of the 16 conditions included in current screening guidelines, most carriers were not from the population the guideline aimed to serve. Conclusion To provide equitable reproductive care, guidelines should discontinue the use of ethnicity as a basis for determining which patients are appropriate for carrier screening and instead recommend pan-ethnic ECS.

Original languageEnglish (US)
JournalUnknown Journal
StatePublished - Dec 27 2019


  • Carrier screening
  • Ethnicity
  • Genetic ancestry
  • Medical guidelines
  • Recessive disease

ASJC Scopus subject areas

  • Medicine(all)

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