23andMe, Sunnyvale, CA.
National Human Genome Research Institute, Social and Behavioral Research Branch, National Institutes of Health, Bethesda, MD.
Blood Adv. 2024 Nov 12;8(21):5710-5718. doi: 10.1182/bloodadvances.2024014252.
Sickle cell trait (SCT) is a risk factor for venous thromboembolism (VTE). Prior studies investigating the association between SCT and VTE have been performed nearly exclusively in Black populations. However, race-based research can contribute to systemic racism in medicine. We leveraged data from the 23andMe research cohort (4 184 082 participants) to calculate the ancestry-independent risk of VTE associated with SCT as well as comparative risk estimates for heterozygous factor V Leiden (FVL). Odds ratios (ORs) were calculated using a meta-analysis of 3 genetic ancestry groups (European [n = 3 183 142], Latine [n = 597 539], and African [n = 202 281]) and a secondary full-cohort analysis including 2 additional groups (East Asian [n = 159 863] and South Asian [n = 41 257]). Among the full cohort, 94 323 participants (2.25%) reported a history of VTE. On meta-analysis, individuals with SCT had a 1.45-fold (confidence interval [CI], 1.32-1.60) increased risk of VTE compared with SCT noncarriers, which was similar to the full-cohort estimate. The risk of pulmonary embolism (PE) in SCT (OR, 1.95; CI, 1.72-2.20) was higher than that of isolated deep venous thrombosis (DVT; OR, 1.04; CI, 0.90-1.21). FVL carriers had 3.30-fold (CI, 3.24-3.37) increased risk of VTE compared with FVL noncarriers, with a higher risk of isolated DVT (OR, 3.59; CI, 3.51-3.68) than PE (OR, 2.72; CI, 2.64-2.81). In this large, diverse cohort, the risk of VTE was increased among individuals with SCT compared with those without, independent of race or genetic ancestry. The risk of VTE with SCT was lower than that observed in FVL; however, the pattern of VTE in SCT was PE predominant, which is the opposite to that observed in FVL.
镰状细胞特征（SCT）是静脉血栓栓塞症（VTE）的一个风险因素。先前研究 SCT 与 VTE 之间关联的研究几乎都是在黑人人群中进行的。然而，基于种族的研究可能会导致医学中的系统性种族主义。我们利用 23andMe 研究队列（4184082 名参与者）的数据来计算与 SCT 相关的 VTE 的无种族相关性风险，以及杂合子因子 V 莱顿（FVL）的相对风险估计值。使用 3 个遗传祖先群体（欧洲[ n = 3183142]、拉丁裔[ n = 597539]和非洲裔[ n = 202281]）的荟萃分析和包括另外 2 个组（东亚[ n = 159863]和南亚[ n = 41257]）的二次全队列分析计算比值比（ORs）。在全队列中，94323 名参与者（2.25%）报告有 VTE 病史。荟萃分析显示，与非 SCT 携带者相比，SCT 携带者的 VTE 风险增加 1.45 倍（置信区间[CI]，1.32-1.60），这与全队列的估计值相似。SCT 患者的肺栓塞（PE）风险（OR，1.95；CI，1.72-2.20）高于孤立性深静脉血栓形成（DVT；OR，1.04；CI，0.90-1.21）。与 FVL 非携带者相比，FVL 携带者的 VTE 风险增加 3.30 倍（CI，3.24-3.37），且孤立性 DVT 的风险更高（OR，3.59；CI，3.51-3.68），而 PE 的风险较低（OR，2.72；CI，2.64-2.81）。在这个大型、多样化的队列中，与无 SCT 个体相比，SCT 个体的 VTE 风险增加，而与种族或遗传祖先无关。SCT 个体的 VTE 风险低于 FVL 观察到的风险；然而，SCT 中的 VTE 模式以 PE 为主，与 FVL 观察到的相反。
