Jun Xiang, Guangming Xiang, Ming Zhan, Lingyun Zhang, Huaqian Zeng, Xinyu Song
{"title":"抗精神病药物靶基因与肺癌风险的关联：孟德尔随机研究。","authors":"Jun Xiang, Guangming Xiang, Ming Zhan, Lingyun Zhang, Huaqian Zeng, Xinyu Song","doi":"10.1007/s12672-025-03659-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic drugs are associated with various tumors, but their causal relationship with lung cancer risk remains unclear. We aimed to investigate this association using Mendelian randomization (MR) analyses.</p><p><strong>Methods: </strong>We performed summary-data-based MR (SMR) using blood-derived expression quantitative trait loci (eQTL) and two sample-MR using single nucleotide polymorphism (SNP) of antipsychotic drug target genes. Colocalization analysis was performed with cis-eQTLs, and sensitivity analyses included the Heterogeneity in dependent instruments (HEIDI) test and Multi-SNP-based SMR.</p><p><strong>Results: </strong>SMR showed that higher DRD4 expression was associated with lower lung cancer risk (P<sub>SMR</sub> = 0.009; P<sub>HEIDI</sub> >0.01; P<sub>SMR</sub>_multi = 0.0338). Two-sample MR further indicated inverse associations for KCNH2 (OR: 0.91; 95%CI: 0.83-0.99; P = 0.040) and DRD4 (OR: 0.89; 95%CI: 0.79-0.99; P = 0.040) with lung cancer risk. Additionally, elevated HTR6 and DRD4 expression was linked to decreased lung adenocarcinoma (LUAD) risk (HTR6, OR: 0.89; 95%CI: 0.81-0.99; P = 0.014; DRD4, OR: 0.87; 95%CI: 0.76-0.98; P = 0.016). Colocalization analyses did not support shared causal variants (PP.H4 < 0.8).</p><p><strong>Conclusion: </strong>These findings provide insights into the potential oncologic implications of antipsychotic drug use and may inform clinical management.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"1925"},"PeriodicalIF":2.9000,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540951/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of antipsychotic drug target genes and risk of lung cancer: a Mendelian randomization study.\",\"authors\":\"Jun Xiang, Guangming Xiang, Ming Zhan, Lingyun Zhang, Huaqian Zeng, Xinyu Song\",\"doi\":\"10.1007/s12672-025-03659-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Antipsychotic drugs are associated with various tumors, but their causal relationship with lung cancer risk remains unclear. We aimed to investigate this association using Mendelian randomization (MR) analyses.</p><p><strong>Methods: </strong>We performed summary-data-based MR (SMR) using blood-derived expression quantitative trait loci (eQTL) and two sample-MR using single nucleotide polymorphism (SNP) of antipsychotic drug target genes. Colocalization analysis was performed with cis-eQTLs, and sensitivity analyses included the Heterogeneity in dependent instruments (HEIDI) test and Multi-SNP-based SMR.</p><p><strong>Results: </strong>SMR showed that higher DRD4 expression was associated with lower lung cancer risk (P<sub>SMR</sub> = 0.009; P<sub>HEIDI</sub> >0.01; P<sub>SMR</sub>_multi = 0.0338). Two-sample MR further indicated inverse associations for KCNH2 (OR: 0.91; 95%CI: 0.83-0.99; P = 0.040) and DRD4 (OR: 0.89; 95%CI: 0.79-0.99; P = 0.040) with lung cancer risk. Additionally, elevated HTR6 and DRD4 expression was linked to decreased lung adenocarcinoma (LUAD) risk (HTR6, OR: 0.89; 95%CI: 0.81-0.99; P = 0.014; DRD4, OR: 0.87; 95%CI: 0.76-0.98; P = 0.016). Colocalization analyses did not support shared causal variants (PP.H4 < 0.8).</p><p><strong>Conclusion: </strong>These findings provide insights into the potential oncologic implications of antipsychotic drug use and may inform clinical management.</p>\",\"PeriodicalId\":11148,\"journal\":{\"name\":\"Discover. Oncology\",\"volume\":\"16 1\",\"pages\":\"1925\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540951/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Discover. Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12672-025-03659-w\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Discover. Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12672-025-03659-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Association of antipsychotic drug target genes and risk of lung cancer: a Mendelian randomization study.
Background: Antipsychotic drugs are associated with various tumors, but their causal relationship with lung cancer risk remains unclear. We aimed to investigate this association using Mendelian randomization (MR) analyses.
Methods: We performed summary-data-based MR (SMR) using blood-derived expression quantitative trait loci (eQTL) and two sample-MR using single nucleotide polymorphism (SNP) of antipsychotic drug target genes. Colocalization analysis was performed with cis-eQTLs, and sensitivity analyses included the Heterogeneity in dependent instruments (HEIDI) test and Multi-SNP-based SMR.
Results: SMR showed that higher DRD4 expression was associated with lower lung cancer risk (PSMR = 0.009; PHEIDI >0.01; PSMR_multi = 0.0338). Two-sample MR further indicated inverse associations for KCNH2 (OR: 0.91; 95%CI: 0.83-0.99; P = 0.040) and DRD4 (OR: 0.89; 95%CI: 0.79-0.99; P = 0.040) with lung cancer risk. Additionally, elevated HTR6 and DRD4 expression was linked to decreased lung adenocarcinoma (LUAD) risk (HTR6, OR: 0.89; 95%CI: 0.81-0.99; P = 0.014; DRD4, OR: 0.87; 95%CI: 0.76-0.98; P = 0.016). Colocalization analyses did not support shared causal variants (PP.H4 < 0.8).
Conclusion: These findings provide insights into the potential oncologic implications of antipsychotic drug use and may inform clinical management.
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