Cullina Sinead, Wojcik Genevieve L, Shemirani Ruhollah, Klarin Derek, Gorman Bryan R, Sorokin Elena P, Gignoux Christopher R, Belbin Gillian M, Pyarajan Saiju, Asgari Samira, Tsao Philip S, Damrauer Scott M, Abul-Husn Noura S, Kenny Eimear E
Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Genet. 2023 Aug 1;14:1181167. doi: 10.3389/fgene.2023.1181167. eCollection 2023.
Peripheral artery disease (PAD) is a form of atherosclerotic cardiovascular disease, affecting ∼8 million Americans, and is known to have racial and ethnic disparities. PAD has been reported to have a significantly higher prevalence in African Americans (AAs) compared to non-Hispanic European Americans (EAs). Hispanic/Latinos (HLs) have been reported to have lower or similar rates of PAD compared to EAs, despite having a paradoxically high burden of PAD risk factors; however, recent work suggests prevalence may differ between sub-groups. Here, we examined a large cohort of diverse adults in the Bio biobank in New York City. We observed the prevalence of PAD at 1.7% in EAs vs. 8.5% and 9.4% in AAs and HLs, respectively, and among HL sub-groups, the prevalence was found at 11.4% and 11.5% in Puerto Rican and Dominican populations, respectively. Follow-up analysis that adjusted for common risk factors demonstrated that Dominicans had the highest increased risk for PAD relative to EAs [OR = 3.15 (95% CI 2.33-4.25), < 6.44 × 10]. To investigate whether genetic factors may explain this increased risk, we performed admixture mapping by testing the association between local ancestry and PAD in Dominican Bio participants (N = 1,813) separately from European, African, and Native American (NAT) continental ancestry tracts. The top association with PAD was an NAT ancestry tract at chromosome 2q35 [OR = 1.96 (SE = 0.16), < 2.75 × 10) with 22.6% vs. 12.9% PAD prevalence in heterozygous NAT tract carriers versus non-carriers, respectively. Fine-mapping at this locus implicated tag SNP rs78529201 located within a long intergenic non-coding RNA (lincRNA) , a gene expression regulator of key genes related to thrombosis and extracellular remodeling of endothelial cells, suggesting a putative link of the 2q35 locus to PAD etiology. Efforts to reproduce the signal in other Hispanic cohorts were unsuccessful. In summary, we showed how leveraging health system data helped understand nuances of PAD risk across HL sub-groups and admixture mapping approaches elucidated a putative risk locus in a Dominican population.
外周动脉疾病（PAD）是动脉粥样硬化性心血管疾病的一种形式，影响着约800万美国人，并且已知存在种族和族裔差异。据报道，与非西班牙裔欧洲裔美国人（EAs）相比，非裔美国人（AAs）的PAD患病率显著更高。据报道，西班牙裔/拉丁裔（HLs）与EAs相比，PAD发病率较低或相近，尽管他们患有矛盾的高负担PAD风险因素；然而，最近的研究表明，不同亚组之间的患病率可能有所不同。在这里，我们研究了纽约市生物样本库中一大群不同的成年人。我们观察到EAs的PAD患病率为1.7%，而AAs和HLs的患病率分别为8.5%和9.4%，在HL亚组中，波多黎各人和多米尼加人群的患病率分别为11.4%和11.5%。对常见风险因素进行调整的随访分析表明，相对于EAs，多米尼加人患PAD的风险增加最高[比值比（OR）=3.15（95%置信区间2.33 - 4.25），<6.44×10]。为了研究遗传因素是否可以解释这种风险增加，我们通过分别测试多米尼加生物样本参与者（N = 1813）中本地血统与PAD之间的关联，与欧洲、非洲和美洲原住民（NAT）大陆血统区域进行混合映射。与PAD的最高关联是2号染色体q35区域的NAT血统区域[OR = 1.96（标准误=0.16），<2.75×10]，杂合NAT区域携带者与非携带者的PAD患病率分别为22.6%和12.9%。该位点的精细定位涉及位于长链基因间非编码RNA（lincRNA）内的标签单核苷酸多态性（SNP）rs78529201，lincRNA是与血栓形成和内皮细胞细胞外重塑相关关键基因的基因表达调节剂，这表明2q35位点与PAD病因之间存在推定联系。在其他西班牙裔队列中重现该信号的努力未成功。总之，我们展示了利用卫生系统数据如何有助于理解HL亚组中PAD风险的细微差别，以及混合映射方法如何阐明多米尼加人群中的一个推定风险位点。
