Purpose

Carrier status associates strongly with genetic ancestry, yet current carrier screening guidelines recommend testing for a limited set of conditions based on a patient’s self-reported ethnicity. Ethnicity, which can reflect both genetic ancestry and cultural factors (e.g., religion), may be imperfectly known or communicated by patients. We sought to quantitatively assess the efficacy and equity with which ethnicity-based carrier screening captures recessive disease risk.

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. 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 7 of the 16 conditions included in current screening guidelines, most carriers were not from the population the guideline aimed to serve.

Conclusion

Substantial and disproportionate risk for recessive disease is not detected when carrier screening is based on ethnicity, leading to inequitable reproductive care.

中文翻译：

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对超过 93,000 名接受扩大携带者筛查的个体的遗传血统分析揭示了基于种族的医学指南的局限性。

目的

携带者状态与遗传血统密切相关，但目前的携带者筛查指南建议根据患者自我报告的种族对一组有限的条件进行测试。种族，可以反映遗传血统和文化因素（例如，宗教），患者可能不完全了解或交流。我们试图定量评估基于种族的携带者筛查捕捉隐性疾病风险的有效性和公平性。

方法

对于接受 96 基因扩展携带者筛查 (ECS) 的 93,419 名个体，评估了携带者状态、自我报告的种族和根据测序数据计算的双组分遗传血统（例如，75% 非洲人/25% 欧洲人）之间的对应关系。

结果

自我报告的种族是遗传血统的不完美指标，有 9% 的个体具有 >50% 的遗传血统，其血统与自我报告的种族不一致。自我报告种族的局限性导致高危人群中遗漏携带者：对于 10 种 ECS 疾病，具有中等遗传血统背景的患者（未自我报告相关种族）的携带者风险显着升高。最后，对于当前筛查指南中包含的 16 种疾病中的 7 种，大多数携带者并非来自指南旨在服务的人群。

结论

当基于种族进行携带者筛查时，未检测到隐性疾病的显着和不成比例的风险，从而导致不公平的生殖保健。