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Although genome\u2010wide association studies have nominated reproducible susceptibility loci and high\u2010throughput profiling has expanded the landscape of circulating, imaging, vascular and skeletal muscle biomarkers, most signals are noncoding, mechanistic attribution is often uncertain and few biomarkers have demonstrated durable incremental utility for risk stratification or therapeutic guidance in routine care. In this review, we summarise PAD\u2010relevant genetic architectures and multiomics modalities\u2014fine\u2010mapped GWAS with tissue\u2010 and cell\u2010resolved functional genomics, proteogenomic and metabolomic profiling and network\u2010based integration across vascular, muscle and circulating compartments\u2014and we appraise translational opportunities that span variant\u2010anchored protein and metabolite prioritisation, composite biomarker panels for limb\u2010specific ischaemic burden and residual atherothrombotic risk and biomarker\u2010informed selection of antithrombotic, lipid\u2010lowering, anti\u2010inflammatory and revascularisation strategies. We also discuss enduring challenges\u2014including ancestry\u2010sensitive transferability of genetic instruments, limited access to disease\u2010relevant tissues, cross\u2010platform standardisation, confounding by disease stage and therapy and the need for prospective validation and trial\u2010ready pharmacodynamic endpoints\u2014that temper implementation. The purpose of this review is to delineate variant\u2010to\u2010biomarker pathways in PAD and specify integrative, clinically actionable solutions for discovery, validation and translation. We further distinguish diagnostic, prognostic, predictive\/theragnostic and pharmacodynamic biomarker contexts of use, and emphasise that phenotype definition, sex, diabetes, exposure measurement and treatment effects all condition the interpretation and transferability of PAD multiomic signals.<\/jats:p>","DOI":"10.1155\/humu\/1908331","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:21:31Z","timestamp":1777468891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Variant\u2010to\u2010Biomarker Pathways in Peripheral Artery Disease: Multiomics Integration and Clinical Translation"],"prefix":"10.1155","volume":"2026","author":[{"given":"Wanting","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7871-2663","authenticated-orcid":false,"given":"Changxin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5656-5385","authenticated-orcid":false,"given":"Siyao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2017.07.018"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303849"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30255-4"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(23)00355-8"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.2.197"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.13415"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.11.1317"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2016.263798"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X251330583"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.09.004"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415569348"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.210385"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj295"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2014.06.029"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0492-5"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002862"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.787545"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0519-3"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-015-0050-4"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8091463"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.758085"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-025-00709-y"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01250-y"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.322325"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02247-3"},{"key":"e_1_2_12_26_2","first-page":"67","volume-title":"Advances in Clinical Chemistry","author":"Ismaeel A.","year":"2022"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2015.71"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2013.04.022"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-023-02029-3"},{"key":"e_1_2_12_30_2","article-title":"Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients With Peripheral Artery Disease","volume":"9","author":"Azab S. 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