Pub Date : 2018-09-15DOI: 10.1183/13993003.congress-2018.pa1275
D. V. D. Plaat, Miguel Pereira, G. Pesce, J. Potts, A. Amaral, S. Dharmage, J. Garcia-Aymerich, F. Gómez-Real, D. Jarvis, C. Minelli, B. Leynaert
{"title":"Age at menopause and lung function: A Mendelian randomization study","authors":"D. V. D. Plaat, Miguel Pereira, G. Pesce, J. Potts, A. Amaral, S. Dharmage, J. Garcia-Aymerich, F. Gómez-Real, D. Jarvis, C. Minelli, B. Leynaert","doi":"10.1183/13993003.congress-2018.pa1275","DOIUrl":"https://doi.org/10.1183/13993003.congress-2018.pa1275","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45737977","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.OA2192
C. Minelli, D. V. D. Plaat, B. Leynaert, R. Granell, A. Amaral, Miguel Pereira, O. Mahmoud, J. Potts, John F. Thompson, D. Jarvis, G. Davey-Smith, J. Henderson
Evidence on whether early puberty increases the risk of adult asthma is suggestive but inconclusive in women, and very scarce in men. To overcome the issue of residual confounding in observational studies and provide evidence on casual effects, we used Mendelian randomization (MR) with 332 SNPs as instrumental variables for age at menarche in women, and 18 SNPs for age at voice breaking in men. Age at menarche was categorised as early ( 14), while age at voice breaking was recorded and analysed as at a younger, average or older age. Based on 243,316 women and 192,067 men from UK Biobank (9.2% and 6.3% with post-pubertal asthma, respectively), we find detrimental effects of early puberty on asthma. In women, an 8% increase in asthma risk for early and an 8% decrease for late menarche suggest a linear effect of pubertal timing. Similar effects are observed in males, even though the power is lower and the confidence intervals much wider (Figure). There is evidence of modest pleiotropy, but our findings are consistent across different methods robust to pleiotropy (Figure). We show detrimental effects of early puberty on asthma. As similar patterns are seen in both sexes, the effect in women is unlikely to be mediated by female sex hormones as hypothesised, suggesting instead a role of common (biological or psychological) factors related to early physical development. [ALEC, EU Grant #633212]
关于青春期提前是否会增加成人哮喘风险的证据在女性中具有启发性，但尚无定论，而在男性中则非常少。为了克服观察性研究中的残留混淆问题，并为随机效应提供证据，我们使用孟德尔随机化(MR)方法，其中332个snp作为女性月经初来年龄的工具变量，18个snp作为男性破音年龄的工具变量。初潮时的年龄被归类为早(14岁)，而破嗓时的年龄被记录和分析为更年轻、平均或更年长。基于来自UK Biobank的243316名女性和192067名男性(分别为9.2%和6.3%的青春期后哮喘患者)，我们发现青春期早期对哮喘的有害影响。在女性中，月经初潮早的哮喘风险增加8%，月经初潮晚的哮喘风险降低8%，这表明青春期时间有线性影响。在男性中也观察到类似的效果，尽管其功率较低，置信区间更宽(图)。有证据表明存在适度的多效性，但我们的发现在不同的多效性检测方法中是一致的(图)。我们发现青春期提前对哮喘有不利影响。由于在两性中都发现了类似的模式，对女性的影响不太可能像假设的那样由女性性激素介导，而是表明与早期身体发育有关的共同(生物或心理)因素的作用。[ALEC, EU Grant #633212]
{"title":"The effect of early puberty on asthma in women and men: A Mendelian randomization study","authors":"C. Minelli, D. V. D. Plaat, B. Leynaert, R. Granell, A. Amaral, Miguel Pereira, O. Mahmoud, J. Potts, John F. Thompson, D. Jarvis, G. Davey-Smith, J. Henderson","doi":"10.1183/13993003.CONGRESS-2018.OA2192","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.OA2192","url":null,"abstract":"Evidence on whether early puberty increases the risk of adult asthma is suggestive but inconclusive in women, and very scarce in men. To overcome the issue of residual confounding in observational studies and provide evidence on casual effects, we used Mendelian randomization (MR) with 332 SNPs as instrumental variables for age at menarche in women, and 18 SNPs for age at voice breaking in men. Age at menarche was categorised as early ( 14), while age at voice breaking was recorded and analysed as at a younger, average or older age. Based on 243,316 women and 192,067 men from UK Biobank (9.2% and 6.3% with post-pubertal asthma, respectively), we find detrimental effects of early puberty on asthma. In women, an 8% increase in asthma risk for early and an 8% decrease for late menarche suggest a linear effect of pubertal timing. Similar effects are observed in males, even though the power is lower and the confidence intervals much wider (Figure). There is evidence of modest pleiotropy, but our findings are consistent across different methods robust to pleiotropy (Figure). We show detrimental effects of early puberty on asthma. As similar patterns are seen in both sexes, the effect in women is unlikely to be mediated by female sex hormones as hypothesised, suggesting instead a role of common (biological or psychological) factors related to early physical development. [ALEC, EU Grant #633212]","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43934880","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.PA1277
M. Wielscher, C. Minelli, A. Amaral, Juha Auwinen, S. Sebert, D. Jarvis, M. Järvelin
Background: Observational studies show that lung function is associated with cardio metabolic traits (e.g. BMI, coronary artery disease, type 2 diabetes, blood pressure) and markers of systemic inflammation (e.g. CRP). However, these associations may be confounded by shared risk factors (e.g. smoking). In this study we investigated whether the associations of lung function with cardio metabolic traits may be causal. Methods: We selected instrumental variables from published large scale genome-wide association studies, including SNPs with P Results: MR estimates suggest a negative association of BMI with FEV1 and FVC and a positive association with FEV1/FVC (P Conclusion: We show, by using genetic instruments, that the observational associations of BMI, T2D, SBP, CRP and lung function are unlikely to be confounded and may be causal. Investigation of possible pleiotropic effects are currently being performed to further explore these findings. Funding: EU H2020 grant 633212
{"title":"Cardio metabolic traits and lung function: A Mendelian Randomization study","authors":"M. Wielscher, C. Minelli, A. Amaral, Juha Auwinen, S. Sebert, D. Jarvis, M. Järvelin","doi":"10.1183/13993003.CONGRESS-2018.PA1277","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.PA1277","url":null,"abstract":"Background: Observational studies show that lung function is associated with cardio metabolic traits (e.g. BMI, coronary artery disease, type 2 diabetes, blood pressure) and markers of systemic inflammation (e.g. CRP). However, these associations may be confounded by shared risk factors (e.g. smoking). In this study we investigated whether the associations of lung function with cardio metabolic traits may be causal. Methods: We selected instrumental variables from published large scale genome-wide association studies, including SNPs with P Results: MR estimates suggest a negative association of BMI with FEV1 and FVC and a positive association with FEV1/FVC (P Conclusion: We show, by using genetic instruments, that the observational associations of BMI, T2D, SBP, CRP and lung function are unlikely to be confounded and may be causal. Investigation of possible pleiotropic effects are currently being performed to further explore these findings. Funding: EU H2020 grant 633212","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45349873","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.OA2188
L. Wain, N. Shrine, A. Guyatt, V. Jackson, A. Erzurumluoglu, C. Batini, N. Reeve, B. Hobbs, M. Cho, D. Strachan, A. Morris, I. Hall, M. Tobin
Lung function measures are used in diagnosis and grading of COPD. We have previously shown that the genetic determinants of lung function, analysed in large general population cohorts, are informative about risk of COPD and a powerful alternative to case-control studies. We previously reported a significant association (P=5.65x10-36) with COPD for an unweighted genetic risk score based on the 95 variants reported as associated with lung function at that time. We undertook genome-wide association analyses of spirometry in 404,165 individuals from UK Biobank and the SpiroMeta consortium to identify novel signals (P We identified 139 novel signals which we combined with the 140 previously reported signals to construct a weighted risk score that was then tested for association with COPD in a combined analysis of 5991 COPD cases and 3378 controls. The mean (SD) number of risk alleles per individual across the 279 signals was 295 (10.4). The weighted risk score was significantly associated with risk of COPD (P=6.64x10-63), with an OR of 1.55 (95% confidence intervals 1.47, 1.63) for each standard deviation of the risk score (approximately 12 risk alleles). Our findings show that increasing the number of signals in a weighted risk score increases predictive power for COPD, and provides new biological insight.
{"title":"A weighted genetic risk score based on 279 signals of association with lung function predicts Chronic Obstructive Pulmonary Disease","authors":"L. Wain, N. Shrine, A. Guyatt, V. Jackson, A. Erzurumluoglu, C. Batini, N. Reeve, B. Hobbs, M. Cho, D. Strachan, A. Morris, I. Hall, M. Tobin","doi":"10.1183/13993003.CONGRESS-2018.OA2188","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.OA2188","url":null,"abstract":"Lung function measures are used in diagnosis and grading of COPD. We have previously shown that the genetic determinants of lung function, analysed in large general population cohorts, are informative about risk of COPD and a powerful alternative to case-control studies. We previously reported a significant association (P=5.65x10-36) with COPD for an unweighted genetic risk score based on the 95 variants reported as associated with lung function at that time. We undertook genome-wide association analyses of spirometry in 404,165 individuals from UK Biobank and the SpiroMeta consortium to identify novel signals (P We identified 139 novel signals which we combined with the 140 previously reported signals to construct a weighted risk score that was then tested for association with COPD in a combined analysis of 5991 COPD cases and 3378 controls. The mean (SD) number of risk alleles per individual across the 279 signals was 295 (10.4). The weighted risk score was significantly associated with risk of COPD (P=6.64x10-63), with an OR of 1.55 (95% confidence intervals 1.47, 1.63) for each standard deviation of the risk score (approximately 12 risk alleles). Our findings show that increasing the number of signals in a weighted risk score increases predictive power for COPD, and provides new biological insight.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47950948","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.PA1264
R. Kelly, S. Weiss, B. Levy, B. Raby, J. Lasky-Su
Rationale: FADS2 encodes a crucial rate limiting enzyme within omega-3/6 fatty acid pathways, and has been linked to asthma. Metabolomics is ideally suited to explore the downstream implications of FADS2 variants on the asthmatic phenotype. Methods: Blood collected at recruitment in the Childhood Asthma Management Program was submitted for metabolomic and genome-wide profiling. Metabolite Quantitative Trait Loci (mQTL) analysis was used to identify metabolites associated with 72 SNPs in FADS2. Mediation analysis was conducted to determine if the genetic burden of airway obstruction was mediated through alterations in these metabolites. Results: 495 asthmatic children, including 59 with airway obstruction (%predicted FEV1/FVC Conclusions: We leveraged integrative-omic data to demonstrate mQTLs near FADS2 may drive differential abundance of key inflammatory metabolites influencing asthma. The balance of omega-3/6 fatty acid conversion regulated by FADS2 is crucial for the resolution of inflammation and dampening of airway hyper-responsiveness. However, FADS2 likely exerts its influence through other metabolomic pathways.
{"title":"Metabolite quantitative trait loci provide functional link between FADS2 and lung obstruction in asthmatics","authors":"R. Kelly, S. Weiss, B. Levy, B. Raby, J. Lasky-Su","doi":"10.1183/13993003.CONGRESS-2018.PA1264","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.PA1264","url":null,"abstract":"Rationale: FADS2 encodes a crucial rate limiting enzyme within omega-3/6 fatty acid pathways, and has been linked to asthma. Metabolomics is ideally suited to explore the downstream implications of FADS2 variants on the asthmatic phenotype. Methods: Blood collected at recruitment in the Childhood Asthma Management Program was submitted for metabolomic and genome-wide profiling. Metabolite Quantitative Trait Loci (mQTL) analysis was used to identify metabolites associated with 72 SNPs in FADS2. Mediation analysis was conducted to determine if the genetic burden of airway obstruction was mediated through alterations in these metabolites. Results: 495 asthmatic children, including 59 with airway obstruction (%predicted FEV1/FVC Conclusions: We leveraged integrative-omic data to demonstrate mQTLs near FADS2 may drive differential abundance of key inflammatory metabolites influencing asthma. The balance of omega-3/6 fatty acid conversion regulated by FADS2 is crucial for the resolution of inflammation and dampening of airway hyper-responsiveness. However, FADS2 likely exerts its influence through other metabolomic pathways.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49569270","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.PA1266
M. D. Vries, V. Guryev, T. D. Jong, J. Vonk, H. Boezen, C. V. Diemen
It has been postulated that abnormal ageing is involved in the disease pathogenesis of chronic obstructive pulmonary disease (COPD). While most studies assess differences in senescence and known ageing genes, we recently developed a new approach to measure ageing markers at DNA level using whole genome sequencing (WGS). In this study, we aim to test if these ageing markers are associated with COPD. WGS was performed on 36 non-smoking subjects with COPD (FEV1/FVC We found a significant shorter telomere length, more loss of X-chromosome and more loss of mitochondrial DNA in the COPD subjects, while the AluY retrotransposition activity was higher in the COPD subjects compared to the healthy controls. Interestingly, these results are in line with the observations in ageing hallmarks in the general population. Although T-cell proportion is expected to decrease with ageing, we did not find any differences for this marker between COPD subjects and healthy controls. Based on the estimation of ageing markers at DNA level, our study shows differences in ageing in COPD subjects compared to healthy controls. Results of our new approach confirm previous hypotheses that ageing might indeed be involved in COPD.
{"title":"DNA-estimated ageing markers are associated with COPD","authors":"M. D. Vries, V. Guryev, T. D. Jong, J. Vonk, H. Boezen, C. V. Diemen","doi":"10.1183/13993003.CONGRESS-2018.PA1266","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.PA1266","url":null,"abstract":"It has been postulated that abnormal ageing is involved in the disease pathogenesis of chronic obstructive pulmonary disease (COPD). While most studies assess differences in senescence and known ageing genes, we recently developed a new approach to measure ageing markers at DNA level using whole genome sequencing (WGS). In this study, we aim to test if these ageing markers are associated with COPD. WGS was performed on 36 non-smoking subjects with COPD (FEV1/FVC We found a significant shorter telomere length, more loss of X-chromosome and more loss of mitochondrial DNA in the COPD subjects, while the AluY retrotransposition activity was higher in the COPD subjects compared to the healthy controls. Interestingly, these results are in line with the observations in ageing hallmarks in the general population. Although T-cell proportion is expected to decrease with ageing, we did not find any differences for this marker between COPD subjects and healthy controls. Based on the estimation of ageing markers at DNA level, our study shows differences in ageing in COPD subjects compared to healthy controls. Results of our new approach confirm previous hypotheses that ageing might indeed be involved in COPD.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43553940","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.PA1273
Xingnan Li, S. Guerra, Huashi Li, S. Christenson, R. Barr, C. Cooper, D. Couper, M. Dransfield, M. Han, N. Hansel, E. Hoffman, R. Kanner, E. Kleerup, F. Martinez, W. O’Neal, R. Paine, P. Woodruff, D. Meyers, E. Bleecker
{"title":"Genomic analysis of CC16 as a biomarker for COPD","authors":"Xingnan Li, S. Guerra, Huashi Li, S. Christenson, R. Barr, C. Cooper, D. Couper, M. Dransfield, M. Han, N. Hansel, E. Hoffman, R. Kanner, E. Kleerup, F. Martinez, W. O’Neal, R. Paine, P. Woodruff, D. Meyers, E. Bleecker","doi":"10.1183/13993003.CONGRESS-2018.PA1273","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.PA1273","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43186991","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.PA1267
Chiara Rigobello, S. Baraldo, M. Tiné, I. Ferrarotti, A. Corsico, D. Biondini, D. Lacedonia, G. E. Carpagnano, M. Barbaro, G. Valle, M. Saetta, M. Cosio
{"title":"Exome sequencing reveals immune genes as susceptibility modifiers in a1-antitrypsin deficiency","authors":"Chiara Rigobello, S. Baraldo, M. Tiné, I. Ferrarotti, A. Corsico, D. Biondini, D. Lacedonia, G. E. Carpagnano, M. Barbaro, G. Valle, M. Saetta, M. Cosio","doi":"10.1183/13993003.CONGRESS-2018.PA1267","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.PA1267","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49200876","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 : 2018-09-15DOI: 10.1183/13993003.congress-2018.pa1274
C. Eichstaedt, Luca Pagani, T. Antão, Charlotte E. Inchley, A. Cardona, A. Mörseburg, F. Clemente, T. Sluckin, E. Metspalu, M. Mitt, R. Mägi, G. Hudjashov, M. Metspalu, Maru Mormina, G. Jacobs, T. Kivisild
{"title":"New evidence of genetic adaptation to high altitude in Andean populations","authors":"C. Eichstaedt, Luca Pagani, T. Antão, Charlotte E. Inchley, A. Cardona, A. Mörseburg, F. Clemente, T. Sluckin, E. Metspalu, M. Mitt, R. Mägi, G. Hudjashov, M. Metspalu, Maru Mormina, G. Jacobs, T. Kivisild","doi":"10.1183/13993003.congress-2018.pa1274","DOIUrl":"https://doi.org/10.1183/13993003.congress-2018.pa1274","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43057152","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 : 2018-09-15DOI: 10.1183/13993003.CONGRESS-2018.PA1269
N. Mookherjee, M. Ryu, M. Hemshekhar, V. Spicer, C. Carlsten
Introduction: Diesel exhaust (DE), a paradigm for traffic-related air pollution, is associated with respiratory and cardiovascular diseases. The aim of this study was to define changes in global proteins (proteome) in plasma following exposure to inhaled DE, using a controlled human exposure study. Methods: Ex-smokers (n=6) inhaled filtered air (FA) and DE (300 mg PM2.5/m3) for 2h (crossover; random order). Plasma was obtained 24h after each exposure. Plasma (n=12) were probed in Slow off-rate modified aptamer (SOMAmer®)-based proteomic array. Differential analysis with Welch’s t-test was used to identify proteins significantly altered by inhaled DE compared to FA. Abundance of selected proteins were independently quantified using ELISA or immunoblots, in plasma obtained from healthy individuals following DE and FA exposure, to further validate proteins enhanced by DE. Results: 342 plasma proteins were significantly altered by DE compared to FA (Fig. 1). The top 20 proteins enhanced by DE were enriched to GO biological process of immune response; inflammation or cardiovascular disease. Conclusion: This is the first comprehensive interrogation of the plasma proteome to identify proteins altered following inhaled DE exposure in humans, and adds functional plausibility to observations of adverse health effects therein.
{"title":"Inhaled diesel exhaust alters plasma proteome signature","authors":"N. Mookherjee, M. Ryu, M. Hemshekhar, V. Spicer, C. Carlsten","doi":"10.1183/13993003.CONGRESS-2018.PA1269","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.PA1269","url":null,"abstract":"Introduction: Diesel exhaust (DE), a paradigm for traffic-related air pollution, is associated with respiratory and cardiovascular diseases. The aim of this study was to define changes in global proteins (proteome) in plasma following exposure to inhaled DE, using a controlled human exposure study. Methods: Ex-smokers (n=6) inhaled filtered air (FA) and DE (300 mg PM2.5/m3) for 2h (crossover; random order). Plasma was obtained 24h after each exposure. Plasma (n=12) were probed in Slow off-rate modified aptamer (SOMAmer®)-based proteomic array. Differential analysis with Welch’s t-test was used to identify proteins significantly altered by inhaled DE compared to FA. Abundance of selected proteins were independently quantified using ELISA or immunoblots, in plasma obtained from healthy individuals following DE and FA exposure, to further validate proteins enhanced by DE. Results: 342 plasma proteins were significantly altered by DE compared to FA (Fig. 1). The top 20 proteins enhanced by DE were enriched to GO biological process of immune response; inflammation or cardiovascular disease. Conclusion: This is the first comprehensive interrogation of the plasma proteome to identify proteins altered following inhaled DE exposure in humans, and adds functional plausibility to observations of adverse health effects therein.","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45002286","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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