Pub Date : 2022-03-29DOI: 10.1186/s41021-022-00240-7
A. Hakura, Naoki Koyama, Yuki Seki, J. Sonoda, S. Asakura
{"title":"o-Aminoazotoluene, 7,12-dimethylbenz[a]anthracene, and N-ethyl-N-nitrosourea, which are mutagenic but not carcinogenic in the colon, rapidly induce colonic tumors in mice with dextran sulfate sodium-induced colitis","authors":"A. Hakura, Naoki Koyama, Yuki Seki, J. Sonoda, S. Asakura","doi":"10.1186/s41021-022-00240-7","DOIUrl":"https://doi.org/10.1186/s41021-022-00240-7","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47996388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-01DOI: 10.1183/13993003.congress-2020.4920
E. Slob, A. Faiz, S. Vijverberg, C. Longo, Mehmet Kutlu, Patricia Soares, F. Chew, E. Herrera-Luis, Antonio Espuela Ortiz, Maria Del Pino Yanes, E. Burchard, U. Potočnik, C. Palmer, C. Maroteau, S. Turner, K. Verhamme, Leila Karimi, S. Mukhopadhyay, W. Timens, P. Hiemstra, M. Pijnenburg, M. Berge, A. M. Zee, G. Koppelman
{"title":"Bronchial airway inducible expression and methylation QTL mapping identifies a single nucleotide polymorphism predicting inhaled corticosteroids response heterogeneity","authors":"E. Slob, A. Faiz, S. Vijverberg, C. Longo, Mehmet Kutlu, Patricia Soares, F. Chew, E. Herrera-Luis, Antonio Espuela Ortiz, Maria Del Pino Yanes, E. Burchard, U. Potočnik, C. Palmer, C. Maroteau, S. Turner, K. Verhamme, Leila Karimi, S. Mukhopadhyay, W. Timens, P. Hiemstra, M. Pijnenburg, M. Berge, A. M. Zee, G. Koppelman","doi":"10.1183/13993003.congress-2020.4920","DOIUrl":"https://doi.org/10.1183/13993003.congress-2020.4920","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"1 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46481996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-12DOI: 10.1186/s41021-019-0134-7
M. Kawanishi
{"title":"The 32nd summer school of the Research Community for Mechanisms of Mutations","authors":"M. Kawanishi","doi":"10.1186/s41021-019-0134-7","DOIUrl":"https://doi.org/10.1186/s41021-019-0134-7","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"41 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2019-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41021-019-0134-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41906632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5396
H. Niu, T. Yang, W. Niu, K. Huang, R. Duan, T. Yu, Chen Wang
Background: Although some studies have evaluated the association of the receptor for advanced glycation end products (RAGE) genetic variation with asthma and COPD, the results are still inconsistent. We here aimed to investigate the association of multiple variants in RAGE gene with the risk for asthma and COPD, alone and in combination, in a population-based Han Chinese cohort. Methods: Five variants in RAGE gene (rs1800625, rs1800624, rs2070600, rs184003 and rs2071288) were genotyped using the TaqMan assay among 347 patients with asthma or COPD and 527 age and sex-matched controls. Data were analyzed using Haplo.stats program, and a nomogram model was created to predict asthma and COPD risk. Results: The genotypic distributions of five selected variants met the Hardy-Weinberg equilibrium. In single-locus analysis, statistically significant differences were seen in the allele distribution of rs1800625 in COPD and rs1800624 in asthma between patients and controls. Haplotype analysis indicated that haplotypes T-A-G-T-G (in order of rs1800625, rs1800624, rs2070600, rs184003 and rs2071288 variants) (Padj. = 0.0134) and T-A-A-G-G (P adj. = 0.0040) conferred a decrease risk for COPD and asthma respectively. Haplotype-phenotype analysis indicated significant association of high- and low-density lipoprotein cholesterol and blood urea nitrogen with COPD and total cholesterol with asthma (Psim Conclusions: Our findings indicate that RAGE gene is a candidate gene in susceptibility to the development of asthma and COPD in Han Chinese.
{"title":"Association of RAGE gene multiple variants with the risk for asthma and COPD in a population-based Han Chinese cohort","authors":"H. Niu, T. Yang, W. Niu, K. Huang, R. Duan, T. Yu, Chen Wang","doi":"10.1183/13993003.congress-2019.pa5396","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5396","url":null,"abstract":"Background: Although some studies have evaluated the association of the receptor for advanced glycation end products (RAGE) genetic variation with asthma and COPD, the results are still inconsistent. We here aimed to investigate the association of multiple variants in RAGE gene with the risk for asthma and COPD, alone and in combination, in a population-based Han Chinese cohort. Methods: Five variants in RAGE gene (rs1800625, rs1800624, rs2070600, rs184003 and rs2071288) were genotyped using the TaqMan assay among 347 patients with asthma or COPD and 527 age and sex-matched controls. Data were analyzed using Haplo.stats program, and a nomogram model was created to predict asthma and COPD risk. Results: The genotypic distributions of five selected variants met the Hardy-Weinberg equilibrium. In single-locus analysis, statistically significant differences were seen in the allele distribution of rs1800625 in COPD and rs1800624 in asthma between patients and controls. Haplotype analysis indicated that haplotypes T-A-G-T-G (in order of rs1800625, rs1800624, rs2070600, rs184003 and rs2071288 variants) (Padj. = 0.0134) and T-A-A-G-G (P adj. = 0.0040) conferred a decrease risk for COPD and asthma respectively. Haplotype-phenotype analysis indicated significant association of high- and low-density lipoprotein cholesterol and blood urea nitrogen with COPD and total cholesterol with asthma (Psim Conclusions: Our findings indicate that RAGE gene is a candidate gene in susceptibility to the development of asthma and COPD in Han Chinese.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42917683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5399
T. Beiko, D. Woodford, C. Strange
Background: Chronic illness is associated with vulnerability for anxiety disorders. Anxiety can negatively affect patient-reported outcomes. Aims: We hypothesized that anxiety prevalence will vary in a population tested for alpha-1 antitrypsin deficiency (AATD) based on age, gender, smoking status, and quality of life. We sought to determine if AAT genotype was independently related to anxiety. Methods: The Alpha Coded Testing (ACT) study offers confidential testing for AATD in individuals with diagnosed COPD and in AATD families. Psychosocial surveys, demographics, income and smoking status were collected. Multivariable analysis analyzed anxiety correlations as defined by Beck Anxiety Inventory (BAI) >22. A p-value Results: 1452 subjects had AATD genotype testing finding MM genotype in 50%, MZ in 36%, MS in 6%, ZZ in 4%, SZ in 2.5%. 1.5% had Znull, Mnull, or SS genotypes. Among AATD individuals or carriers, 9.2% had high BAI scores. In univariate analysis, anxiety was more prevalent in females (64% of study population) (OR=2.15; p Conclusions: Anxiety is common in those tested for AATD. Smoking status and income influence the prevalence of anxiety among populations tested for AATD. AAT genotypes and gender did not correlate with BAI scores in multivariate analyses. Strong correlation of high anxiety and SF12 scores was driven by MCS component.
{"title":"Anxiety in a population tested for alpha-1 antitrypsin deficiency","authors":"T. Beiko, D. Woodford, C. Strange","doi":"10.1183/13993003.congress-2019.pa5399","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5399","url":null,"abstract":"Background: Chronic illness is associated with vulnerability for anxiety disorders. Anxiety can negatively affect patient-reported outcomes. Aims: We hypothesized that anxiety prevalence will vary in a population tested for alpha-1 antitrypsin deficiency (AATD) based on age, gender, smoking status, and quality of life. We sought to determine if AAT genotype was independently related to anxiety. Methods: The Alpha Coded Testing (ACT) study offers confidential testing for AATD in individuals with diagnosed COPD and in AATD families. Psychosocial surveys, demographics, income and smoking status were collected. Multivariable analysis analyzed anxiety correlations as defined by Beck Anxiety Inventory (BAI) >22. A p-value Results: 1452 subjects had AATD genotype testing finding MM genotype in 50%, MZ in 36%, MS in 6%, ZZ in 4%, SZ in 2.5%. 1.5% had Znull, Mnull, or SS genotypes. Among AATD individuals or carriers, 9.2% had high BAI scores. In univariate analysis, anxiety was more prevalent in females (64% of study population) (OR=2.15; p Conclusions: Anxiety is common in those tested for AATD. Smoking status and income influence the prevalence of anxiety among populations tested for AATD. AAT genotypes and gender did not correlate with BAI scores in multivariate analyses. Strong correlation of high anxiety and SF12 scores was driven by MCS component.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43576867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5387
A. Fialkovska, S. Ilchenko
{"title":"The genetic risk factors for developing chronic bronchitis in adolescent smokers","authors":"A. Fialkovska, S. Ilchenko","doi":"10.1183/13993003.congress-2019.pa5387","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5387","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45473927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5393
R. Vernet, P. Margaritte-Jeannin, R. Matran, F. Zerimech, V. Siroux, M. Dizier, R. Nadif, F. Demenais, E. Bouzigon
Background: Eosinophils play a key role in the allergic response in asthma by the release of cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. Objective: Our goal was to identify genetic variants influencing ECP and EDN levels. Methods: We conducted univariate and bivariate genome-wide association analyses of ECP and EDN levels measured in plasma in 1018 adults (451 with asthma) from the EGEA cohort using 1000-Genomes imputed SNPs. Results: The univariate analyses detected two genome-wide significant loci associated with ECP on chromosomes 14q11 (rs7141958 located between RNASE3 and RNASE2, P=3.9x10-13) and 18q21 near MC4R (rs9959588, P=1.7x10-9) and one significant locus at 14q11 associated with EDN near RNASE2 (rs67049014, P=1.6x10-12). The bivariate analysis detected the two previous loci plus a third one on 1p31 (rs57716204 in AK4, P=1.6x10-8). Fine-mapping of these regions, based on bivariate conditional analysis, showed that the 14q11 region contained three distinct signals located 76kb apart: the lead SNP rs67049014 and two other SNPs, rs76185655 and rs28525131. Interrogation of eQTL databases showed that the lead SNP was associated with the expression of RNASE2, RNASE3 and METTL17 (P Conclusion: The joint analysis of biomarkers involved in the same pathway can increase power to detect new loci and can help refining associated regions. Replication of these results is ongoing.
{"title":"New genetic variants associated with eosinophil cationic protein and eosinophil-derived neurotoxin levels identified through bivariate genome-wide association study","authors":"R. Vernet, P. Margaritte-Jeannin, R. Matran, F. Zerimech, V. Siroux, M. Dizier, R. Nadif, F. Demenais, E. Bouzigon","doi":"10.1183/13993003.congress-2019.pa5393","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5393","url":null,"abstract":"Background: Eosinophils play a key role in the allergic response in asthma by the release of cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. Objective: Our goal was to identify genetic variants influencing ECP and EDN levels. Methods: We conducted univariate and bivariate genome-wide association analyses of ECP and EDN levels measured in plasma in 1018 adults (451 with asthma) from the EGEA cohort using 1000-Genomes imputed SNPs. Results: The univariate analyses detected two genome-wide significant loci associated with ECP on chromosomes 14q11 (rs7141958 located between RNASE3 and RNASE2, P=3.9x10-13) and 18q21 near MC4R (rs9959588, P=1.7x10-9) and one significant locus at 14q11 associated with EDN near RNASE2 (rs67049014, P=1.6x10-12). The bivariate analysis detected the two previous loci plus a third one on 1p31 (rs57716204 in AK4, P=1.6x10-8). Fine-mapping of these regions, based on bivariate conditional analysis, showed that the 14q11 region contained three distinct signals located 76kb apart: the lead SNP rs67049014 and two other SNPs, rs76185655 and rs28525131. Interrogation of eQTL databases showed that the lead SNP was associated with the expression of RNASE2, RNASE3 and METTL17 (P Conclusion: The joint analysis of biomarkers involved in the same pathway can increase power to detect new loci and can help refining associated regions. Replication of these results is ongoing.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44602740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5388
Leila Karimi, S. Vijverberg, M. Engelkes, N. Hernandez-Pacheco, N. Farzan, Patricia Soares, Ben Francis, M. Pino-Yanes, C. Eng, S. Mukhopadhyay, M. Schieck, M. Kabesch, E. Burchard, C. Palmer, S. Turner, H. Janssens, A. M. Zee, K. Verhamme
Background: The association of haplotype combinations of polymorphisms at positions 16 and 27 of the β2-adrenergic receptor (ADRB2) gene and the risk of asthma exacerbations among users of long-acting β2-agonists (LABA) is still unclear. Aim: We investigated the association between these haplotypes of the ADRB2 gene and asthma exacerbations in asthmatic patients using LABA and inhaled corticosteroids (ICS) from the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Methods: We conducted a meta-analysis of 880 children and young adults aged (4-21) with asthma treated with LABA and ICS. We extracted two polymorphisms; rs1042713 (16Arg>Gly) and rs1042714 (27Gln>Glu) in the ADRB2 gene. Asthma exacerbations were defined as prescribed courses of oral corticosteroids and/or asthma-related hospitalizations/emergency room visits in the past 6 or 12 months prior to the study visit. The association between the haplotypes and asthma exacerbations was performed by using the Haplo-Stats package adjusted for age and sex. A meta-analysis was performed using an inverse variance–weighted method assuming a random-effect. Results: Three haplotypes were determined; Gly16Glu27, Arg16Gln27 and Gly16Gln27. Compared to the Gly16Glu27 haplotype, the Arg16Gln27 haplotype was significantly associated with an increased risk of asthma exacerbations (OR:1.37, 95%CI;1.03-1.81, P=0.028, I2=0.0%). Conclusion: We found that the Arg haplotype (Arg16Gln27) in the ADRB2 gene increased the risk of exacerbations among users of LABA and ICS. Whether or not this argues against use of LABA in patients with this haplotype needs further research.
{"title":"ADRB2 haplotypes and risk of exacerbations in asthmatic children and young adults treated with long-acting ß2-agonists: A meta-analysis in the PiCA consortium","authors":"Leila Karimi, S. Vijverberg, M. Engelkes, N. Hernandez-Pacheco, N. Farzan, Patricia Soares, Ben Francis, M. Pino-Yanes, C. Eng, S. Mukhopadhyay, M. Schieck, M. Kabesch, E. Burchard, C. Palmer, S. Turner, H. Janssens, A. M. Zee, K. Verhamme","doi":"10.1183/13993003.congress-2019.pa5388","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5388","url":null,"abstract":"Background: The association of haplotype combinations of polymorphisms at positions 16 and 27 of the β2-adrenergic receptor (ADRB2) gene and the risk of asthma exacerbations among users of long-acting β2-agonists (LABA) is still unclear. Aim: We investigated the association between these haplotypes of the ADRB2 gene and asthma exacerbations in asthmatic patients using LABA and inhaled corticosteroids (ICS) from the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Methods: We conducted a meta-analysis of 880 children and young adults aged (4-21) with asthma treated with LABA and ICS. We extracted two polymorphisms; rs1042713 (16Arg>Gly) and rs1042714 (27Gln>Glu) in the ADRB2 gene. Asthma exacerbations were defined as prescribed courses of oral corticosteroids and/or asthma-related hospitalizations/emergency room visits in the past 6 or 12 months prior to the study visit. The association between the haplotypes and asthma exacerbations was performed by using the Haplo-Stats package adjusted for age and sex. A meta-analysis was performed using an inverse variance–weighted method assuming a random-effect. Results: Three haplotypes were determined; Gly16Glu27, Arg16Gln27 and Gly16Gln27. Compared to the Gly16Glu27 haplotype, the Arg16Gln27 haplotype was significantly associated with an increased risk of asthma exacerbations (OR:1.37, 95%CI;1.03-1.81, P=0.028, I2=0.0%). Conclusion: We found that the Arg haplotype (Arg16Gln27) in the ADRB2 gene increased the risk of exacerbations among users of LABA and ICS. Whether or not this argues against use of LABA in patients with this haplotype needs further research.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43051974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5395
L. Wain, A. Erzurumluoglu, C. Melbourne, D. Doiron, K. Hoogh, M. Tobin, A. Hansell
Air pollution has been found to be associated with reduced lung function; also 279 genetic signals of association with lung function have been identified that implicate multiple genes and pathways. In this study, we examined if any of these signals interact with air pollution measures NO2, PM2.5 and PM10. In 259,389 unrelated European individuals from UK Biobank, we tested for a gene-environment interaction effect on lung function with NO2, PM2.5 and PM10 for each of the 279 signals. Lung function measures (FEV1, FEV1/FVC and FVC) were adjusted for sex, age, age2, height, and smoking, income and educational status, with adjustment for 15 principal components for fine-scale population structure. A significance threshold of P We found statistically significant evidence for an interaction with PM2.5 on FEV1/FVC for rs10841302 on chromosome 12 (minor allele frequency=45.2%, interaction P=1.55x10-5). The SNP was also nominally significant for an interaction with PM10 and NO2 (P=5.2x10-4 and 2.3x10-3, respectively). This SNP did not show an interaction with tobacco smoke in a previous analysis. A further 16 SNPs had a nominally significant (P The gene underlying the association of rs10841302 with lung function has not been determined but the SNP lies close to the AEBP2 gene which encodes AE Binding Protein 2, a transcriptional repressor which may have a role in histone methylation. Identification and characterisation of genes whose effect is influenced by air pollution exposure will enable us to understand how the environment influences respiratory health.
{"title":"Interaction with air pollution exposure for genetic loci associated with lung function","authors":"L. Wain, A. Erzurumluoglu, C. Melbourne, D. Doiron, K. Hoogh, M. Tobin, A. Hansell","doi":"10.1183/13993003.congress-2019.pa5395","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5395","url":null,"abstract":"Air pollution has been found to be associated with reduced lung function; also 279 genetic signals of association with lung function have been identified that implicate multiple genes and pathways. In this study, we examined if any of these signals interact with air pollution measures NO2, PM2.5 and PM10. In 259,389 unrelated European individuals from UK Biobank, we tested for a gene-environment interaction effect on lung function with NO2, PM2.5 and PM10 for each of the 279 signals. Lung function measures (FEV1, FEV1/FVC and FVC) were adjusted for sex, age, age2, height, and smoking, income and educational status, with adjustment for 15 principal components for fine-scale population structure. A significance threshold of P We found statistically significant evidence for an interaction with PM2.5 on FEV1/FVC for rs10841302 on chromosome 12 (minor allele frequency=45.2%, interaction P=1.55x10-5). The SNP was also nominally significant for an interaction with PM10 and NO2 (P=5.2x10-4 and 2.3x10-3, respectively). This SNP did not show an interaction with tobacco smoke in a previous analysis. A further 16 SNPs had a nominally significant (P The gene underlying the association of rs10841302 with lung function has not been determined but the SNP lies close to the AEBP2 gene which encodes AE Binding Protein 2, a transcriptional repressor which may have a role in histone methylation. Identification and characterisation of genes whose effect is influenced by air pollution exposure will enable us to understand how the environment influences respiratory health.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48607674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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