{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:45:29Z","timestamp":1791938729484,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Acne vulgaris presents a substantial clinical challenge due to its complex pathophysiology and significant impact on quality of life. Identification of novel therapeutic targets for acne using genetic tools can guide the development of more effective treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Utilizing a dataset comprising 35\u2009559 Icelandic individuals, we performed proteomic analyses to quantify 4709 circulating proteins. We integrated these data with acne\u2010specific genome\u2010wide association studies (GWAS) encompassing 34\u2009422 acne patients and 364\u2009991 controls. Mendelian randomization (MR) analyses employed the TwoSampleMR tool and Summary\u2010data\u2010based Mendelian Randomization (SMR) to estimate the causal effects of identified proteins on acne risk. Colocalization analyses assessed the likelihood of shared genetic etiology between protein levels and acne using the \u201ccoloc\u201d R package.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our proteome\u2010wide MR analysis initially identified 128 proteins potentially associated with acne risk. Following multiple testing corrections using the Benjamini\u2013Hochberg method, fatty acid synthase (FASN) and tissue inhibitor of metalloproteinases 4 (TIMP4) remained significantly associated with acne risk. FASN exhibited a protective effect against acne (OR\u2009=\u20090.768, 95% CI: 0.676\u20130.872, <jats:italic>p<\/jats:italic>\u2009=\u20094.685E\u201005), while TIMP4 was associated with an increased risk (OR\u2009=\u20091.169, 95% CI: 1.103\u20131.241, <jats:italic>p<\/jats:italic>\u2009=\u20091.956E\u201007). Colocalization analysis supported a shared genetic basis for these protein\u2010acne associations, with posterior probabilities indicating strong evidence of shared causal variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings highlight the utility of integrative genomic approaches in identifying potential therapeutic targets for acne. FASN and TIMP4, in particular, demonstrate strong potential as targets for therapeutic intervention, pending further validation through clinical research. These results offer a foundation for targeted acne treatment development, aligning with personalized medicine principles.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jocd.16567","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T08:53:47Z","timestamp":1726736027000},"page":"4223-4229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring Genetic Drug Targets in Acne Vulgaris: A Comprehensive Proteome\u2010Wide Mendelian Randomization Study"],"prefix":"10.1111","volume":"23","author":[{"given":"Ruyi","family":"Ju","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine Zhejiang Chinese Medical University  Hangzhou City Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuou","family":"Ying","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine Zhejiang Chinese Medical University  Hangzhou City Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-3423","authenticated-orcid":false,"given":"Qiujun","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine Zhejiang Chinese Medical University  Hangzhou City Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cao","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University and the First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou City Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(11)60321\u20108"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14475"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13462"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12149"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.090374"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.01.092"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.15862"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq098"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016010098"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010021\u201000978\u2010w"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010023\u201001326\u20108"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.12788\/j.sder.2018.024"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S424478"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12224"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000068476"},{"key":"e_1_2_8_17_1","first-page":"247","article-title":"Acne: A New Model of Immune\u2010Mediated Chronic Inflammatory Skin Disease","volume":"150","author":"Antiga E.","year":"2015","journal-title":"Giornale Italiano Di Dermatologia E Venereologia: Organo Ufficiale, Societa Italiana Di Dermatologia E Sifilografia"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476\u20104598\u20107\u201085"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249739"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.4161\/derm.3.1.13900"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010006\u20107893\u2010x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.09.013"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0253915"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005763"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.14749"},{"key":"e_1_2_8_26_1","first-page":"967","article-title":"Polymorphisms in the Promoters of MMP\u20102 and TIMP\u20102 Genes in Patients With Acne Vulgaris","volume":"6","author":"Yaykasli K. 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