Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysis
While the association between smoking and accelerated facial aging is well documented, the specific pathways underlying this association remain poorly understood. To investigate the shared genetic architecture between smoking and facial aging, we performed genetic analyses based on genome-wide assoc...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037025003162 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849389177869697024 |
|---|---|
| author | Xueyao Cai Weidong Li Wenjun Shi Yuchen Cai Jianda Zhou |
| author_facet | Xueyao Cai Weidong Li Wenjun Shi Yuchen Cai Jianda Zhou |
| author_sort | Xueyao Cai |
| collection | DOAJ |
| description | While the association between smoking and accelerated facial aging is well documented, the specific pathways underlying this association remain poorly understood. To investigate the shared genetic architecture between smoking and facial aging, we performed genetic analyses based on genome-wide association studies (GWAS) data. These analyses included linkage disequilibrium score regression (LDSC), pleiotropic analysis under composite null hypothesis (PLACO), functional mapping and annotation (FUMA), and multi-marker analysis of genomic annotation (MAGMA). To further explore the shared target genes, we utilized expression quantitative trait loci (eQTLs) and mediation Mendelian randomization (MR) analysis, with subsequent validation conducted through in vitro experiments using NIH/3T3 cells. Additionally, we carried out pan-cancer correlation analyses to assess the broader implications of the identified genes in cancer biology. Through pleiotropy and colocalization analyses, IREB2, along with CHRNA5 and AARS1, were identified as having strong evidence linking smoking and facial aging. Functional enrichment, tissue-specific analyses, and gene co-expression network were conducted to further elucidate the functions of these genes. Following eQTLs and mediation analyses, IREB2 was identified as a potential mediator connecting smoking to facial aging. Cellular experiments demonstrated that exposure to cigarette smoke particles induces cellular senescence and downregulates IREB2 expression. The pan-cancer analysis highlighted IREB2's role in shaping the tumor microenvironment and influencing immune processes. This study identifies IREB2 as a critical factor in the molecular mechanisms by which smoking accelerates facial aging, while also contributing to tumor development and immune evasion. Further functional exploration of IREB2 could uncover new therapeutic avenues to address these interconnected conditions. |
| format | Article |
| id | doaj-art-2b4d4c5c265c4bfc847e913a00af4ead |
| institution | Kabale University |
| issn | 2001-0370 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj-art-2b4d4c5c265c4bfc847e913a00af4ead2025-08-20T03:42:02ZengElsevierComputational and Structural Biotechnology Journal2001-03702025-01-01273433344210.1016/j.csbj.2025.07.049Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysisXueyao Cai0Weidong Li1Wenjun Shi2Yuchen Cai3Jianda Zhou4Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Correspondence to: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Huangpu District, Shanghai 200011, China.Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; Correspondence to: Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China.While the association between smoking and accelerated facial aging is well documented, the specific pathways underlying this association remain poorly understood. To investigate the shared genetic architecture between smoking and facial aging, we performed genetic analyses based on genome-wide association studies (GWAS) data. These analyses included linkage disequilibrium score regression (LDSC), pleiotropic analysis under composite null hypothesis (PLACO), functional mapping and annotation (FUMA), and multi-marker analysis of genomic annotation (MAGMA). To further explore the shared target genes, we utilized expression quantitative trait loci (eQTLs) and mediation Mendelian randomization (MR) analysis, with subsequent validation conducted through in vitro experiments using NIH/3T3 cells. Additionally, we carried out pan-cancer correlation analyses to assess the broader implications of the identified genes in cancer biology. Through pleiotropy and colocalization analyses, IREB2, along with CHRNA5 and AARS1, were identified as having strong evidence linking smoking and facial aging. Functional enrichment, tissue-specific analyses, and gene co-expression network were conducted to further elucidate the functions of these genes. Following eQTLs and mediation analyses, IREB2 was identified as a potential mediator connecting smoking to facial aging. Cellular experiments demonstrated that exposure to cigarette smoke particles induces cellular senescence and downregulates IREB2 expression. The pan-cancer analysis highlighted IREB2's role in shaping the tumor microenvironment and influencing immune processes. This study identifies IREB2 as a critical factor in the molecular mechanisms by which smoking accelerates facial aging, while also contributing to tumor development and immune evasion. Further functional exploration of IREB2 could uncover new therapeutic avenues to address these interconnected conditions.http://www.sciencedirect.com/science/article/pii/S2001037025003162Facial agingSmokingIREB2Mendelian randomizationPan-cancer |
| spellingShingle | Xueyao Cai Weidong Li Wenjun Shi Yuchen Cai Jianda Zhou Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysis Computational and Structural Biotechnology Journal Facial aging Smoking IREB2 Mendelian randomization Pan-cancer |
| title | Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysis |
| title_full | Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysis |
| title_fullStr | Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysis |
| title_full_unstemmed | Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysis |
| title_short | Role of ferroptosis-related IREB2 in the shared genetic etiology between smoking and facial aging: Insights from large-scale genome-wide cross-trait analysis |
| title_sort | role of ferroptosis related ireb2 in the shared genetic etiology between smoking and facial aging insights from large scale genome wide cross trait analysis |
| topic | Facial aging Smoking IREB2 Mendelian randomization Pan-cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2001037025003162 |
| work_keys_str_mv | AT xueyaocai roleofferroptosisrelatedireb2inthesharedgeneticetiologybetweensmokingandfacialaginginsightsfromlargescalegenomewidecrosstraitanalysis AT weidongli roleofferroptosisrelatedireb2inthesharedgeneticetiologybetweensmokingandfacialaginginsightsfromlargescalegenomewidecrosstraitanalysis AT wenjunshi roleofferroptosisrelatedireb2inthesharedgeneticetiologybetweensmokingandfacialaginginsightsfromlargescalegenomewidecrosstraitanalysis AT yuchencai roleofferroptosisrelatedireb2inthesharedgeneticetiologybetweensmokingandfacialaginginsightsfromlargescalegenomewidecrosstraitanalysis AT jiandazhou roleofferroptosisrelatedireb2inthesharedgeneticetiologybetweensmokingandfacialaginginsightsfromlargescalegenomewidecrosstraitanalysis |