Determining Ethnic Disparities Inherent to Tier 3 Vs. Tier 4 Carrier Screening
Vaishali Mehta, Emily B. Rosenfeld, Julia Geltch, Elena AshkinadzeABSTRACT
Objective
To evaluate ethnic disparities in carrier status ascertainment between Tier 3 (conditions with carrier frequency ≥ 1/200) and Tier 4 panels (conditions with carrier frequencies < 1/200), and to assess the utility of Tier 4‐only screening in an ethnically diverse cohort.
Methods
This IRB‐approved retrospective chart review included adults undergoing carrier screening panel between January 2020 and April 2024, with self‐reported ethnicities mapped to regions based on the United Nations Geoscheme, a system to group countries into regions used for analysis. We calculated the prevalence and number needed to screen (NNS) for Tier 4‐only variants across geographic regions and ancestral subgroups.
Results
Among 2000 patients, 65.7% carried at least one Tier 4‐only variant across the cohort, with most ancestral subgroups showing ≥ 60% prevalence. NNS to detect one Tier 4‐only carrier ranged from 1.0 to 2.2, with the greatest efficiency in Africa, Southeast Asia, and Eastern Europe. Carrier couples were identified across multiple regions, with NNS ranging from 7.3 to 58.1.
Conclusions
Tier 3 panels rely on carrier frequency thresholds largely derived from European populations and fail to identify carriers in underrepresented ethnic groups. Tier 4 panels provide greater carrier ascertainment across diverse populations and yield lower NNS. Our data support universal Tier 4 carrier screening.