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Here we characterize smoking-related protein profiles to identify potentially causal biomarkers mediating smoking\u2019s effects. In European-ancestry populations, genetically predicted smoking exposures were significantly associated with levels of 93 (total: 2,922) proteins, including higher levels of asialoglycoprotein receptor 1 (ASGR1). The positive association of ASGR1 levels with ischemic heart disease (IHD) was supported by colocalization (posterior probability of hypothesis 4\u2009=\u20090.91), and was estimated to explain 6.35% (95% confidence interval 2.61\u201310.09%,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20098.77\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    ) of smoking\u2019s effects on IHD in two-step Mendelian randomization analyses. In network analyses, genetically predicted ASGR1 levels were inversely associated with plasma levels of more than 100 proteins, including growth arrest-specific 6, with all these proteins having rs55714927 (that is, a\n                    <jats:italic>cis<\/jats:italic>\n                    -protein quantitative trait locus for ASGR1) as a\n                    <jats:italic>trans<\/jats:italic>\n                    -protein quantitative trait locus. Sensitivity analyses in never-smokers identified a nonstatistically significant residual association between ASGR1 and IHD, which is consistent with possible horizontal pleiotropy, with body mass index implicated as a potential contributing pathway.\n                  <\/jats:p>","DOI":"10.1038\/s44161-026-00871-x","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:03:23Z","timestamp":1790067803000},"page":"999-1015","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteome-wide genetic analyses identify ASGR1 as a potential biomarker linking smoking with ischemic heart disease"],"prefix":"10.1038","volume":"5","author":[{"given":"Alexander C.","family":"Tinworth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andri","family":"Iona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Pozarickij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Von Ende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-0682","authenticated-orcid":false,"given":"Iona Y.","family":"Millwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-0321","authenticated-orcid":false,"given":"Robin G.","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-8241","authenticated-orcid":false,"given":"Robert","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9181-6886","authenticated-orcid":false,"given":"Fiona","family":"Bragg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6423-105X","authenticated-orcid":false,"given":"Zhengming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"871_CR1","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1093\/ntr\/ntab265","volume":"24","author":"H He","year":"2022","unstructured":"He, H. et al. 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