{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T23:14:45Z","timestamp":1783379685641,"version":"3.54.6"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Recent studies have linked modifiable risk factors (RFs) to melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). This study aimed to investigate the causal relationships between 11 modifiable RFs and these skin cancers and to identify novel therapeutic targets using multi-omics approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Exposure data were obtained from genome-wide association studies (GWAS). Mendelian randomization (MR) analyses were performed using the inverse variance weighted (IVW) method as the primary approach, and results from discovery and replication cohorts were combined by meta-analysis. Functional Mapping and Annotation (FUMA) and summary-data-based MR (SMR) were used to prioritize therapeutic targets. Drug prediction, phenome-wide association studies (PheWAS), and single-cell analyses were conducted to evaluate target druggability and biological relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Actinic keratosis (AK) was associated with an increased risk of melanoma (OR = 1.24, 95% CI 1.07-1.43, P &amp;lt; 0.01), whereas alcohol consumption was negatively associated with SCC risk (OR = 0.77, 95% CI 0.62-0.95, P = 0.02). No causal relationships were observed between the investigated RFs and BCC. One potential therapeutic target for melanoma (EDEM2, PSMR = 0.03) and five candidate therapeutic targets for SCC (MAPK3, PSMR = 5.30E-04; NRBP1, PSMR = 4.32E-04; ANKK1, PSMR = 1.89E-06; IL27, PSMR = 3.04E-03; ADH5, PSMR = 0.02) were identified. Drug prediction, PheWAS, and single-cell analyses further supported the therapeutic potential of these genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>AK appears to increase the risk of melanoma, whereas alcohol consumption may be protective against SCC. EDEM2 may represent a potential therapeutic target for melanoma, while MAPK3, NRBP1, ANKK1, IL27, and ADH5 are promising candidate targets for SCC. Further experimental and clinical studies are warranted to validate these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1870725","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:30:29Z","timestamp":1783377029000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Modifiable risk factors and skin cancers: a multi-omics Mendelian randomization study from causal inference to drug target discovery"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhen","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, The Affiliated Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuda","family":"Huoshen","sequence":"additional","affiliation":[{"name":"School of Stomatology, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Stomatology, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Stomatology, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Mucosal Diseases, The Affiliated Stomatology Hospital, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Chengdu Integrated TCM & Western Medicine Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.jaad.2021.03.109","article-title":"United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019","volume":"85","author":"Aggarwal","year":"2021","journal-title":"J. Am. Acad. Dermatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nrg3891","article-title":"The role of regulatory variation in complex traits and disease","volume":"16","author":"Albert","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"636544","DOI":"10.3389\/fcell.2021.636544","article-title":"The tumor microenvironment in SCC: mechanisms and therapeutic opportunities","volume":"9","author":"Am\u00f4r","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1200\/JCO.2013.49.8691","article-title":"Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma","volume":"31","author":"Ascierto","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1001\/jamadermatol.2017.1716","article-title":"Association of multiple primary skin cancers with human immunodeficiency virus infection, CD4 count, and viral load","volume":"153","author":"Asgari","year":"2017","journal-title":"JAMA Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/nbt.4314","article-title":"Dimensionality reduction for visualizing single-cell data using UMAP","volume":"37","author":"Becht","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s00403-021-02309-9","article-title":"Predictors of subsequent primary melanoma: a case-control study","volume":"314","author":"Bellinato","year":"2022","journal-title":"Arch. Dermatol Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1111\/pcmr.12948","article-title":"Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer","volume":"34","author":"Bonilla","year":"2021","journal-title":"Pigment. Cell Melanoma Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"12258","DOI":"10.1038\/ncomms12258","article-title":"Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models","volume":"7","author":"Bottos","year":"2016","journal-title":"Nat. Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1177\/0962280215597579","article-title":"A review of instrumental variable estimators for Mendelian randomization","volume":"26","author":"Burgess","year":"2017","journal-title":"Stat. Methods Med. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1916278","DOI":"10.1080\/19490976.2021.1916278","article-title":"Alcohol as friend or foe in autoimmune diseases: a role for gut microbiome?","volume":"13","author":"Caslin","year":"2021","journal-title":"Gut Microbes"},{"key":"B16","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1186\/s12864-015-2138-4","article-title":"Integrated genomics approach to identify biologically relevant alterations in fewer samples","volume":"16","author":"Chandrani","year":"2015","journal-title":"BMC Genomics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"107471","DOI":"10.1016\/j.dib.2021.107471","article-title":"Dataset of human EDEM2 melanoma cells proteomics, affinity proteomics and deglycoproteomics","volume":"39","author":"Chirioiu","year":"2021","journal-title":"Data Brief."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.3390\/cells11203210","article-title":"Novel approaches in non-melanoma skin Cancers-A focus on Hedgehog pathway in Basal Cell Carcinoma (BCC)","volume":"11","author":"Chmiel","year":"2022","journal-title":"Cells"},{"key":"B19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.canlet.2017.12.020","article-title":"Genetic variant repressing ADH1A expression confers susceptibility to esophageal squamous-cell carcinoma","volume":"421","author":"Cui","year":"2018","journal-title":"Cancer Lett."},{"key":"B20","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1124\/dmd.119.086363","article-title":"Developmental expression of the cytosolic sulfotransferases in human liver","volume":"47","author":"Dubaisi","year":"2019","journal-title":"Drug Metab. Dispos."},{"key":"B22","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.cps.2021.05.001","article-title":"Melanoma risk factors and prevention","volume":"48","author":"Dzwierzynski","year":"2021","journal-title":"Clin. Plast. Surg."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1038\/s41588-021-00978-w","article-title":"Large-scale integration of the plasma proteome with genetics and disease","volume":"53","author":"Ferkingstad","year":"2021","journal-title":"Nat. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/1471-2350-11-64","article-title":"Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis","volume":"11","author":"Ferlini","year":"2010","journal-title":"BMC Med. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"eaag1166","DOI":"10.1126\/scitranslmed.aag1166","article-title":"The druggable genome and support for target identification and validation in drug development","volume":"9","author":"Finan","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"adv00128","DOI":"10.2340\/00015555-3486","article-title":"Actinic keratosis diagnosis and increased risk of developing skin cancer: a 10-year cohort study of 17,651 patients in Sweden","volume":"100","author":"Guorgis","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/S0140-6736(12)60868-X","article-title":"Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial","volume":"380","author":"Hauschild","year":"2012","journal-title":"Lancet"},{"key":"B28","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.bbrc.2019.11.149","article-title":"THG-1 suppresses SALL4 degradation to induce stemness genes and tumorsphere formation through antagonizing NRBP1 in squamous cell carcinoma cells","volume":"523","author":"Hwang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1109\/EICT68394.2025.11355516","article-title":"Machine learning and bioinformatics-driven discovery of biomarkers and therapeutics for Melanoma and Non-Melanoma skin cancers","author":"Jannat","year":"2025"},{"key":"B30","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.jare.2021.06.014","article-title":"Skin cancer biology and barriers to treatment: recent applications of polymeric micro\/nanostructures","volume":"36","author":"Khan","year":"2022","journal-title":"J. Adv. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1111\/php.13245","article-title":"Deciphering UV-induced DNA damage responses to prevent and treat skin cancer","volume":"96","author":"Lee","year":"2020","journal-title":"Photochem Photobiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1001\/archdermatol.2012.1374","article-title":"Smoking and the risk of nonmelanoma skin cancer: systematic review and meta-analysis","volume":"148","author":"Leonardi-Bee","year":"2012","journal-title":"Arch. Dermatol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s12916-023-02881-z","article-title":"The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study","volume":"21","author":"Li","year":"","journal-title":"BMC Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"122011","DOI":"10.1007\/s11356-023-30535-3","article-title":"Childhood sunburn and risk of melanoma and non-melanoma skin cancer: a Mendelian randomization study","volume":"30","author":"Li","year":"","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e1009922","DOI":"10.1371\/journal.pgen.1009922","article-title":"Combining the strengths of inverse-variance weighting and Egger regression in Mendelian randomization using a mixture of regressions model","volume":"17","author":"Lin","year":"2021","journal-title":"PLoS Genet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"116855","DOI":"10.1016\/j.taap.2024.116855","article-title":"Elucidating the relationship between metabolites and breast cancer: a Mendelian randomization study","volume":"484","author":"Lin","year":"2024","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"106652","DOI":"10.1016\/j.jsbmb.2024.106652","article-title":"Drug repurposing opportunities for breast cancer and seven common subtypes","volume":"246","author":"Lin","year":"","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"126349","DOI":"10.1016\/j.envpol.2025.126349","article-title":"Novel insights into the causal relationship between endocrine-disrupting chemicals and breast cancer mediated by circulating metabolites","volume":"375","author":"Lin","year":"","journal-title":"Environ. Pollut."},{"key":"B40","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.pop.2015.07.006","article-title":"Skin cancer","volume":"42","author":"Linares","year":"2015","journal-title":"Prim. Care"},{"key":"B41","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/s41588-018-0144-6","article-title":"Mixed-model association for biobank-scale datasets","volume":"50","author":"Loh","year":"2018","journal-title":"Nat. Genet."},{"key":"B42","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S0140-6736(23)00821-8","article-title":"Cutaneous melanoma","volume":"402","author":"Long","year":"2023","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s10238-025-01562-w","article-title":"Harnessing IL-27: challenges and potential in cancer immunotherapy","volume":"25","author":"Maleki","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"680407","DOI":"10.3389\/fimmu.2021.680407","article-title":"Immunotherapy in acral and mucosal melanoma: current status and future directions","volume":"12","author":"Mao","year":"2021","journal-title":"Front. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1158\/0008-5472.CAN-08-2793","article-title":"Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity","volume":"69","author":"Matsui","year":"2009","journal-title":"Cancer Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"17605","DOI":"10.1038\/s41598-018-35871-w","article-title":"Identification of 55,000 Replicated DNA Methylation QTL","volume":"8","author":"Mcrae","year":"2018","journal-title":"Sci. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.cell.2019.03.025","article-title":"Adaptive immune resistance emerges from tumor-initiating stem cells","volume":"177","author":"Miao","year":"2019","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.2337\/dc21-1705","article-title":"Metabolomics and type 2 diabetes risk: an updated systematic review and meta-analysis of prospective cohort studies","volume":"45","author":"Morze","year":"2022","journal-title":"Diabetes Care"},{"key":"B49","doi-asserted-by":"publisher","first-page":"100125","DOI":"10.1016\/j.mcpro.2021.100125","article-title":"Affinity proteomics and deglycoproteomics uncover novel EDEM2 endogenous substrates and an integrative ERAD network","volume":"20","author":"Munteanu","year":"2021","journal-title":"Mol. Cell Proteomics"},{"key":"B50","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1083\/jcb.201404075","article-title":"EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step","volume":"206","author":"Ninagawa","year":"2014","journal-title":"J. Cell Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1007\/s13277-015-4680-8","article-title":"Adding Mendelian randomization to a meta-analysis-a burgeoning opportunity","volume":"37","author":"Niu","year":"2016","journal-title":"Tumour Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s13073-016-0338-4","article-title":"Predicting gene targets from integrative analyses of summary data from GWAS and eQTL studies for 28 human complex traits","volume":"8","author":"Pavlides","year":"2016","journal-title":"Genome Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1111\/ajd.12282","article-title":"Incidence and prevalence of non-melanoma skin cancer in Australia: a systematic review","volume":"56","author":"Perera","year":"2015","journal-title":"Australas. J. Dermatol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jaad.2021.12.066","article-title":"Skin cancer: primary, secondary, and tertiary prevention. Part I","volume":"87","author":"Perez","year":"2022","journal-title":"J. Am. Acad. Dermatol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41416-018-0105-y","article-title":"Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women study and meta-analysis of prospective studies","volume":"119","author":"Pirie","year":"2018","journal-title":"Br. J. Cancer"},{"key":"B56","doi-asserted-by":"publisher","first-page":"5227","DOI":"10.3390\/ijms22105227","article-title":"Daily lifestyle and cutaneous malignancies","volume":"22","author":"Sawada","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"7650","DOI":"10.1038\/s41467-022-35345-8","article-title":"A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma","volume":"13","author":"Seviiri","year":"2022","journal-title":"Nat. Commun."},{"key":"B58","doi-asserted-by":"publisher","first-page":"7680","DOI":"10.3390\/curroncol29100607","article-title":"Single-cell transcriptomics of endothelial cells in upper and lower human esophageal squamous cell carcinoma","volume":"29","author":"Sha","year":"2022","journal-title":"Curr. Oncol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1056\/NEJMoa1112302","article-title":"Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib","volume":"366","author":"Sosman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1093\/bioinformatics\/btw373","article-title":"PhenoScanner: a database of human genotype-phenotype associations","volume":"32","author":"Staley","year":"2016","journal-title":"Bioinformatics"},{"key":"B61","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B62","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"B63","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jdin.2020.07.004","article-title":"The tumor genetics of acral melanoma: what should a dermatologist know?","volume":"1","author":"Tod","year":"2020","journal-title":"JAAD Int."},{"key":"B64","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.jaad.2009.07.026","article-title":"Spreading pigmented actinic keratosis: a review","volume":"63","author":"Uhlenhake","year":"2010","journal-title":"J. Am. Acad. Dermatol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"B66","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41586-021-03855-y","article-title":"Rare variant contribution to human disease in 281,104 UK biobank exomes","volume":"597","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1007\/s10753-021-01599-5","article-title":"Expressions of Interleukin-27 in oral Lichen planus, oral leukoplakia, and oral squamous cell carcinoma","volume":"45","author":"Wang","year":"2022","journal-title":"Inflammation"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"B69","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1001\/jamapediatrics.2022.5907","article-title":"What parents should know about sun and sunburns in children","volume":"177","author":"Wood","year":"2023","journal-title":"JAMA Pediatr."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1017\/S0033291719002678","article-title":"Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study","volume":"50","author":"Wootton","year":"2020","journal-title":"Psychol. Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.3945\/ajcn.115.115196","article-title":"Alcohol consumption and risk of cutaneous basal cell carcinoma in women and men: 3 prospective cohort studies","volume":"102","author":"Wu","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"B72","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1186\/s12916-020-01778-5","article-title":"Mendelian randomization study of inflammatory bowel disease and bone mineral density","volume":"18","author":"Wu","year":"2020","journal-title":"BMC Med."},{"key":"B73","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/hep.32728","article-title":"The associations between modifiable risk factors and nonalcoholic fatty liver disease: a comprehensive Mendelian randomization study","volume":"77","author":"Xie","year":"2023","journal-title":"Hepatology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"914646","DOI":"10.3389\/fgene.2022.914646","article-title":"Identification of molecular targets and potential mechanisms of yinchen wuling san against head and neck squamous cell carcinoma by network pharmacology and molecular docking","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Genet."},{"key":"B75","doi-asserted-by":"publisher","first-page":"e1003394","DOI":"10.1371\/journal.pmed.1003394","article-title":"The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: a meta-analysis and Mendelian randomisation analysis","volume":"17","author":"Zheng","year":"2020","journal-title":"PLoS Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1038\/s41588-020-0621-6","article-title":"Scalable generalized linear mixed model for region-based association tests in large biobanks and cohorts","volume":"52","author":"Zhou","year":"2020","journal-title":"Nat. Genet."},{"key":"B77","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ng.3538","article-title":"Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets","volume":"48","author":"Zhu","year":"2016","journal-title":"Nat. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1870725\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:30:30Z","timestamp":1783377030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1870725\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":77,"alternative-id":["10.3389\/fgene.2026.1870725"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1870725","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"article-number":"1870725"}}