Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35
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 Americ...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1181167/full |
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| author | Sinead Cullina Sinead Cullina Genevieve L. Wojcik Ruhollah Shemirani Derek Klarin Derek Klarin Bryan R. Gorman Bryan R. Gorman Elena P. Sorokin Christopher R. Gignoux Christopher R. Gignoux Christopher R. Gignoux Gillian M. Belbin Gillian M. Belbin Saiju Pyarajan Saiju Pyarajan Samira Asgari Samira Asgari Philip S. Tsao Scott M. Damrauer Scott M. Damrauer Scott M. Damrauer Noura S. Abul-Husn Noura S. Abul-Husn Eimear E. Kenny Eimear E. Kenny Eimear E. Kenny Eimear E. Kenny |
| author_facet | Sinead Cullina Sinead Cullina Genevieve L. Wojcik Ruhollah Shemirani Derek Klarin Derek Klarin Bryan R. Gorman Bryan R. Gorman Elena P. Sorokin Christopher R. Gignoux Christopher R. Gignoux Christopher R. Gignoux Gillian M. Belbin Gillian M. Belbin Saiju Pyarajan Saiju Pyarajan Samira Asgari Samira Asgari Philip S. Tsao Scott M. Damrauer Scott M. Damrauer Scott M. Damrauer Noura S. Abul-Husn Noura S. Abul-Husn Eimear E. Kenny Eimear E. Kenny Eimear E. Kenny Eimear E. Kenny |
| author_sort | Sinead Cullina |
| collection | DOAJ |
| description | 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 BioMe 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), p < 6.44 × 10−14]. 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 BioMe 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), p < 2.75 × 10−05) 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) LINC00607, 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. |
| first_indexed | 2024-03-12T20:33:34Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T20:33:34Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-b975a7d201e640aeb4ef4ed193aa268e2023-08-01T16:15:43ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-08-011410.3389/fgene.2023.11811671181167Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35Sinead Cullina0Sinead Cullina1Genevieve L. Wojcik2Ruhollah Shemirani3Derek Klarin4Derek Klarin5Bryan R. Gorman6Bryan R. Gorman7Elena P. Sorokin8Christopher R. Gignoux9Christopher R. Gignoux10Christopher R. Gignoux11Gillian M. Belbin12Gillian M. Belbin13Saiju Pyarajan14Saiju Pyarajan15Samira Asgari16Samira Asgari17Philip S. Tsao18Scott M. Damrauer19Scott M. Damrauer20Scott M. Damrauer21Noura S. Abul-Husn22Noura S. Abul-Husn23Eimear E. Kenny24Eimear E. Kenny25Eimear E. Kenny26Eimear E. Kenny27Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United StatesInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesVA Palo Alto Healthcare System, Palo Alto, CA, United StatesDivision of Vascular Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesCenter for Data and Computational Sciences (C-DACS), VA Boston Healthcare System, Boston, MA, United StatesBooz Allen Hamilton, McLean, VA, United StatesDepartment of Genetics, Stanford University, Stanford, CA, United StatesHuman Medical Genetics and Genomics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United States0Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States1Colorado Center for Personalized Medicine, Aurora, CO, United StatesInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States2Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesCenter for Data and Computational Sciences (C-DACS), VA Boston Healthcare System, Boston, MA, United States3Department of Medicine, Brigham Women’s Hospital, Harvard Medical School, Boston, MA, United StatesInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesVA Palo Alto Healthcare System, Palo Alto, CA, United States4Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, United States5Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States6Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United StatesInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States7Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States7Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States2Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesPeripheral 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 BioMe 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), p < 6.44 × 10−14]. 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 BioMe 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), p < 2.75 × 10−05) 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) LINC00607, 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.https://www.frontiersin.org/articles/10.3389/fgene.2023.1181167/fulladmixture mappingperipheral artery diseasebiobanksDominicansgenetic epidemiology |
| spellingShingle | Sinead Cullina Sinead Cullina Genevieve L. Wojcik Ruhollah Shemirani Derek Klarin Derek Klarin Bryan R. Gorman Bryan R. Gorman Elena P. Sorokin Christopher R. Gignoux Christopher R. Gignoux Christopher R. Gignoux Gillian M. Belbin Gillian M. Belbin Saiju Pyarajan Saiju Pyarajan Samira Asgari Samira Asgari Philip S. Tsao Scott M. Damrauer Scott M. Damrauer Scott M. Damrauer Noura S. Abul-Husn Noura S. Abul-Husn Eimear E. Kenny Eimear E. Kenny Eimear E. Kenny Eimear E. Kenny Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35 Frontiers in Genetics admixture mapping peripheral artery disease biobanks Dominicans genetic epidemiology |
| title | Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35 |
| title_full | Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35 |
| title_fullStr | Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35 |
| title_full_unstemmed | Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35 |
| title_short | Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35 |
| title_sort | admixture mapping of peripheral artery disease in a dominican population reveals a putative risk locus on 2q35 |
| topic | admixture mapping peripheral artery disease biobanks Dominicans genetic epidemiology |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1181167/full |
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