{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:59:37Z","timestamp":1785427177052,"version":"3.56.0"},"reference-count":101,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission (HEC) of Pakistan","doi-asserted-by":"crossref","award":["1-8\/HEC\/HRD\/2023\/13078"],"award-info":[{"award-number":["1-8\/HEC\/HRD\/2023\/13078"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1-8\/HEC\/HRD\/2023\/13078"],"award-info":[{"award-number":["1-8\/HEC\/HRD\/2023\/13078"]}],"id":[{"id":"https:\/\/ror.org\/038y3sz68","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An individual\u2019s host genetics influence its susceptibility to both COVID-19 and coronary artery disease (CAD). We analyzed large-scale GWAS datasets encompassing 7.7 million SNPs to identify shared genetic architecture between the two diseases. We identified 24 pleiotropic risk loci for both COVID-19 and CAD, with three loci (1p31.1, 8p21.3, and 18q11.2) showing strong evidence for a single shared causal variant. Loci in the 8p21.3 and 18q11.2 regions showed a bidirectional causal association: COVID-19 to CAD or vice versa, while the 1p31.1 locus only showed a CAD to COVID-19 unilateral casual association in a Mendelian randomization analysis (GSMR). A fine mapping analysis of the three loci identified three lead pleiotropic variants (rs7515509, rs8192330, and rs4800403). The variant rs7515509 was spatially associated with AK5, PIGK, USP33, and ZZZ3; rs8192330 with DMTN, PIWIL2, and several other genes; and rs4800403 with GATA6 and CTAGE1. Transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients validated proxitropic variants (rs8192330 and rs4800403) with distinct expression signatures and prioritized DMTN and PIWIL2 as the likely causal genes. Overexpression of DMTN has been linked to the heme metabolism hallmark, disrupted iron distribution in COVID-19 patients with comorbid CAD, and subsequent stress erythropoiesis, oxidative stress, immunological dysfunction, and altered wound healing, while a lower expression of PIWIL2 has been observed in the cytoplasmic translation and regulation of mRNA metabolism. In conclusion, we identified shared genetic components for COVID-19 and CAD and prioritized DMTN and PIWIL2 as the likely causal genes for the observed shared genetic risk. COVID-19 may act as an acute stressor that unmask or accelerates underlying CAD.<\/jats:p>","DOI":"10.3390\/ijms27094132","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:23:37Z","timestamp":1777987417000},"page":"4132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Post-GWAS Analysis of the Shared Genetic Architecture Between COVID-19 and Coronary Artery Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5656-1323","authenticated-orcid":false,"given":"Muhammad Sarfraz","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA"},{"name":"Department of Biosciences, COMSATS University, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-6714","authenticated-orcid":false,"given":"Waseem","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5074-8525","authenticated-orcid":false,"given":"Sana","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faisalabad Campus, University of Education, Lahore 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3783-1906","authenticated-orcid":false,"given":"Anwaruddin","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani","family":"Manichaikul","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-613X","authenticated-orcid":false,"given":"Weibin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, S.Y., and Yeniova, A.\u00d6. 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