Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.

我们开展了一项全国性研究，针对美国国家骨髓捐赠计划（National Marrow Donor Program）的大型队列（样本量n=1752），对比了自我身份认同与遗传祖先分类结果。本研究旨在明确各类自我身份认同指标与遗传祖先的关联模式，以优化非亲缘骨髓移植的匹配算法。研究对比了多维度的自我身份认同指标（包括种族/族裔与地理祖先）与基于祖先信息标记（Ancestry Informative Markers, AIMs）及移植匹配必需的人类白细胞抗原（Human Leukocyte Antigen, HLA）基因的分类结果。近20%的受访者报告的种族/族裔与地理祖先信息存在不一致。尽管祖先信息标记与人类白细胞抗原结果间存在高度一致性，但所有自我身份认同指标均未与遗传祖先结果完全对应。部分场景下，受访者报告的地理祖先与未通过种族/族裔识别体现的遗传祖先结果一致；但在另一些场景中，地理祖先报告与遗传检测结果几乎无关联，且该差异存在显著的性别区分。不过，当受访者提供其祖父母的祖先信息时，我们观察到可明确划分遗传祖先的个体亚群，这类亚群的人类白细胞抗原频率存在显著差异，这对骨髓移植匹配具有重要参考价值。尽管我们提倡采用定制化问卷以提升祖先信息采集的准确性，但采集捐赠者祖父母的祖先信息，将有助于为更多患者找到匹配的供体，尤其是混血祖先个体。