Genetic ancestry analysis on >93,000 individuals undergoing expanded carrier screening reveals limitations of ethnicity-based medical guidelines.
Genetic ancestry analysis on >93,000 individuals undergoing expanded carrier screening reveals limitations of ethnicity-based medical guidelines.
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DOI：
10.1038/s41436-020-0869-3
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Muzzey D
中科院分区：
文献类型：
--
作者：
Kaseniit KE;Haque IS;Goldberg JD;Shulman LP;Muzzey D
携带者状态与遗传血统密切相关，但当前的携带者筛查指南建议根据患者自我报告的种族对有限的一组疾病进行检测。种族可以反映遗传血统和文化因素（例如宗教），但患者可能并不完全了解或传达。我们试图定量评估基于种族的携带者筛查捕获隐性疾病风险的有效性和公平性。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成分遗传血统（例如 75% 非洲/25% 欧洲）之间的对应性。自我报告的种族并不能完美地反映遗传血统，9% 的人拥有超过 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了携带者：对于 10 种 ECS 情况，具有中间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 种情况中的 7 种，大多数携带者并非来自该指南旨在服务的人群。当基于种族进行携带者筛查时，无法检测到显着且不成比例的隐性疾病风险，从而导致不公平的生殖保健。
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. 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. 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. Substantial and disproportionate risk for recessive disease is not detected when carrier screening is based on ethnicity, leading to inequitable reproductive care.
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