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The aims of our study were (1) to identify proteins associated with alcohol consumption and (2) to investigate the molecular pathways and genetics linking the identified proteins to alcohol consumption and related sociomedical conditions. We generated proteomic and genotypic data from blood samples of 387 Finnish twins (age range: 56\u201370) and calculated polygenic risk scores (PRSs) of eight alcohol\u2010related traits: obesity, alcohol dependence, number of drinks per week, number of cigarettes per day, major depressive disorders (MDDs), schizophrenia, externalising behaviour and educational attainment. We identified 20 (out of 2321) proteins associated with alcohol consumption, expressed as log ethanol grams per month, after Bonferroni correction and adjustment for BMI, sex and age. Within\u2010pair analyses in monozygotic twin pairs showed that some of the identified associations persisted after accounting for genetic confounding. While only the PRS representing genetic risk for the number of alcoholic drinks per week was associated with alcohol consumption, several proteins were associated with PRSs, in particular the PRS of MDD. All identified proteins were significantly replicated in the UK Biobank, and pathway analysis suggested their collective connection to alcohol consumption might be explained by oxidative stress and cell damage. In conclusion, we identified several alcohol\u2010associated plasma proteins whose levels are also linked to genetic risk for mental illness and substance use. Our study suggests the potential of proteins as biomarkers for early detection of alcohol\u2010related disorders.<\/jats:p>","DOI":"10.1111\/adb.70045","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T08:13:27Z","timestamp":1750839207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protein Associations With Alcohol Consumption and Genetic Risk for Alcohol\u2010Related Sociomedical Conditions"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-8483","authenticated-orcid":false,"given":"Gabin","family":"Drouard","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM) HiLIFE, University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-8384","authenticated-orcid":false,"given":"Teemu","family":"Palviainen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM) HiLIFE, University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4452-2380","authenticated-orcid":false,"given":"Chia\u2010Ling","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences University of Connecticut Health Center  Farmington Connecticut USA"},{"name":"The Cato T. 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