{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:00:29Z","timestamp":1780340429593,"version":"3.54.1"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Institutes of Health-National Human Genome Research Institute","award":["R01HG012735"],"award-info":[{"award-number":["R01HG012735"]}]},{"name":"National Institutes of Health-National Institute of General Medical Sciences","award":["R01GM134005"],"award-info":[{"award-number":["R01GM134005"]}]},{"name":"National Institutes of Health-National Heart, Lung, and Blood Institute","award":["R01HL145660"],"award-info":[{"award-number":["R01HL145660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Peripheral artery disease (PAD) is prevalent and frequently co-occurs with type 2 diabetes (T2D) and coronary artery disease (CAD). Although shared genetic factors\u2014pleiotropy\u2014may contribute to these comorbidities, few studies have examined pleiotropy at the transcriptomic and proteomic levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We generated summary statistics for transcriptome-wide (TWAS) and proteome-wide (PWAS) association analyses across PAD, T2D, and CAD. Joint tests for pleiotropy at the variant, transcript, and protein levels were performed using PLACO, and the contributions of these pleiotropic factors to genetic correlations were quantified. Furthermore, we developed pleiotropy models integrating variants, transcripts, and proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the PAD-T2D analysis, we identified 5 SNPs, 2 predicted transcripts, and 2 predicted proteins that together contributed 2.8% to the genome-wide genetic covariance. In the PAD-CAD analysis, 33 SNPs, 2 predicted transcripts, and 2 predicted proteins accounted for 9.15% of the genetic covariance. Overall, eight pleiotropy models were established, providing a multi-layered framework for categorizing our findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Employing a multi-omic framework, this study elucidates the shared genetic architecture of PAD with T2D and CAD. Our findings enhance the understanding of genetic risk factors underlying PAD and its comorbidities, with potential implications for future therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/hmg\/ddag035","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:45:09Z","timestamp":1778845509000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of multi-omic pleiotropy factors for peripheral artery disease"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-7730","authenticated-orcid":false,"given":"Jiaqi","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health , 60 College Street, New Haven, CT 06510 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassius I","family":"Ochoa Chaar","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Yale School of Medicine , 333 Cedar Street, New Haven, CT 06510 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-9607","authenticated-orcid":false,"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale School of Public Health , 60 College Street, New Haven, CT 06510 ,","place":["United States"]},{"name":"Program of Computational Biology and Bioinformatics, Yale University , 300 George Street, New Haven, CT 06511, \u00a0","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T","family":"DeWan","sequence":"additional","affiliation":[{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health , 60 College Street, New Haven, CT 06510 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"2026060114010217400_ref1","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","article-title":"Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis","volume":"382","author":"Fowkes","year":"2013","journal-title":"Lancet"},{"key":"2026060114010217400_ref2","doi-asserted-by":"publisher","first-page":"e1020","DOI":"10.1016\/S2214-109X(19)30255-4","article-title":"Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis","volume":"7","author":"Song","year":"2019","journal-title":"Lancet Glob Health"},{"key":"2026060114010217400_ref3","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s12933-020-01130-4","article-title":"Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis","volume":"19","author":"Chase-Vilchez","year":"2020","journal-title":"Cardiovasc Diabetol"},{"key":"2026060114010217400_ref4","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1161\/ATVBAHA.120.314595","article-title":"Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease","volume":"40","author":"Barnes","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026060114010217400_ref5","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/nrcardio.2016.179","article-title":"Peripheral artery disease: epidemiology and global perspectives","volume":"14","author":"Fowkes","year":"2017","journal-title":"Nat Rev Cardiol"},{"key":"2026060114010217400_ref6","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/s41588-020-0637-y","article-title":"Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis","volume":"52","author":"Vujkovic","year":"2020","journal-title":"Nat Genet"},{"key":"2026060114010217400_ref7","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.2337\/db20-0573","article-title":"The role of TCF7L2 in type 2 diabetes. 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