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In this study, we performed a genome-wide association study meta-analysis, integrated with proteome-wide Mendelian randomization and colocalization analyses, to identify potential therapeutic targets for cutaneous melanoma (CM). Analyzing data from 5527 CM cases and 645 797 controls, we uncovered seven novel genome-wide significant variants linked to CM risk. Additionally, genetically predicted protein levels revealed 15 proteins associated with CM susceptibility, among which ASIP, CD72, CCL11, LYZ, and CCL25 showed the strongest associations. Validation in independent cohorts further supported their potential as biomarkers. Notably, these protein-coding genes are predominantly expressed in macrophages, B cells, CD8 T cells, and malignant cells within CM tissue. Among them, CD72 and LYZ stand out as promising candidates for therapeutic repurposing. These findings enhance our understanding of CM-related genetic and protein biomarkers, providing a foundation for future therapeutic development.<\/jats:p>","DOI":"10.1093\/bib\/bbaf564","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:16:11Z","timestamp":1759925771000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic imputation of transcriptome and proteome illuminates novel therapeutic targets of cutaneous melanoma"],"prefix":"10.1093","volume":"26","author":[{"given":"Yantao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Dermatology , The Third Affiliated Hospital, Sun Yat-sen University, Tianhe District, Guangzhou 510630, Guangdong,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poyee","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Dermatology , Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Luohu District, Shenzhen 518020, Guangdong,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiangya School of Medicine , Central South University, Yuelu District, Changsha 410013, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Rui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Xiangya School of Medicine , Central South University, Yuelu District, Changsha 410013, Hunan,","place":["China"]},{"name":"Xiangya Hospital , Central South University, Kaifu District, Changsha 410008, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zixi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology , The Third Affiliated Hospital, Sun Yat-sen University, Tianhe District, Guangzhou 510630, Guangdong,","place":["China"]},{"name":"Department of Dermatology , The First Affiliated Hospital, Sun Yat-sen University, Yuexiu District, Guangzhou 510080, Guangdong,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danyang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Center of Systems Biology and Data Science , Xiangya School of Medicine, Central South University, Yuelu District, Changsha 410013, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology , Xiangya Hospital, Central South University, Kaifu District, Changsha 410008, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology , Xiangya Hospital, Central South University, Kaifu District, Changsha 410008, Hunan,","place":["China"]},{"name":"Molecular Biology Research Center , Center for Medical Genetics, Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Yuelu District, Changsha 410013, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology , Xiangya Hospital, Central South University, Kaifu District, Changsha 410008, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weichu","family":"Sun","sequence":"additional","affiliation":[{"name":"Xiangya Hospital , Central South University, Kaifu District, Changsha 410008, Hunan,","place":["China"]},{"name":"Department of Spine Surgery , The Second Xiangya Hospital, Central South University, Furong District, Changsha 410011, 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