Genes and Environment最新文献_第9页

TRPM8 polymorphism as an independent factor of bronchial obstruction in asthma TRPM8多态性是哮喘支气管梗阻的独立因素

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 10.1183/13993003.CONGRESS-2018.PA1271

D. Naumov, D. Gassan, O. Kotova, A. Prikhodko, J. Perelman, V. Kolosov

引用次数: 0

Late Breaking Abstract - Associations between a COPD genetic risk score and lung structure on computed tomography (CT): SPIROMICS 最新摘要-计算机断层扫描（CT）上COPD遗传风险评分与肺部结构之间的相关性：SPIROMICS

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 10.1183/13993003.CONGRESS-2018.OA2187

E. Oelsner, Benjamin M. Smith, Jennifer N. Nguyen, A. Manichaikul, E. Hoffman, E. Ampleford, Latchezar Dimitrov, Xiuquing Guo, K. Taylor, E. Bleecker, Xignan Li, D. Meyers, S. Peters, S. Rich, J. Rotter, R. G. Barr, V. Ortega

{"title":"Late Breaking Abstract - Associations between a COPD genetic risk score and lung structure on computed tomography (CT): SPIROMICS","authors":"E. Oelsner, Benjamin M. Smith, Jennifer N. Nguyen, A. Manichaikul, E. Hoffman, E. Ampleford, Latchezar Dimitrov, Xiuquing Guo, K. Taylor, E. Bleecker, Xignan Li, D. Meyers, S. Peters, S. Rich, J. Rotter, R. G. Barr, V. Ortega","doi":"10.1183/13993003.CONGRESS-2018.OA2187","DOIUrl":"https://doi.org/10.1183/13993003.CONGRESS-2018.OA2187","url":null,"abstract":"Background: The extent to which genetic risk of COPD is mediated by variation in lung structure remains unknown. Aims: To determine whether a recently developed genetic risk score for lung function (GRS; Wain LV et al, Nat Genet 2017; 49(3):416-425) is associated with CT lung structure. Methods: In SPIROMICS, a cohort of COPD subjects and at-risk smokers (≥20 pack-years), a weighted GRS was calculated from 83 of 95 single nucleotide polymorphisms genotyped or imputed across 3 race/ethnic groups. Post-bronchodilator spirometry and CT scan measures (via Apollo/VIDA) of lung density, spatially-matched airway dimensions, and small airway counts (generations 6-9) were evaluated in models adjusted for age, age-squared, sex, height, BMI, principal components, smoking status, pack-years, CT model and voxel size. Results: Among 2,579 participants (average age 63 years, 53% male, 76% non-Hispanic White, 18% African-American, 6% Asian, 37% current smokers, median 44 pack-years, 63% with COPD), higher GRS was associated with lower FEV1 and FEV1/FVC, and the highest GRS quintile was associated with doubling of risk for moderate-to-severe COPD (p Conclusions: Variation in lung structure, whether developmental or acquired, is an important mediator of the genetic risk factors underlying 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":"46397760","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}

引用次数: 3

Age at menopause and lung function: A Mendelian randomization study 更年期年龄与肺功能：一项孟德尔随机化研究

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 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

引用次数: 1

The effect of early puberty on asthma in women and men: A Mendelian randomization study 青春期早期对女性和男性哮喘的影响：一项孟德尔随机化研究

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 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

{"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}

引用次数: 1

Cardio metabolic traits and lung function: A Mendelian Randomization study 心脏代谢特征和肺功能:一项孟德尔随机研究

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 10.1183/13993003.CONGRESS-2018.PA1277

M. Wielscher, C. Minelli, A. Amaral, Juha Auwinen, S. Sebert, D. Jarvis, M. Järvelin

引用次数: 0

A weighted genetic risk score based on 279 signals of association with lung function predicts Chronic Obstructive Pulmonary Disease 基于279个与肺功能相关信号的加权遗传风险评分预测慢性阻塞性肺疾病

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 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

{"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}

引用次数: 3

Metabolite quantitative trait loci provide functional link between FADS2 and lung obstruction in asthmatics 代谢产物定量特征基因座在哮喘患者的FADS2和肺阻塞之间提供了功能联系

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 10.1183/13993003.CONGRESS-2018.PA1264

R. Kelly, S. Weiss, B. Levy, B. Raby, J. Lasky-Su

{"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}

引用次数: 1

DNA-estimated ageing markers are associated with COPD DNA估计的衰老标志物与COPD相关

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 10.1183/13993003.CONGRESS-2018.PA1266

M. D. Vries, V. Guryev, T. D. Jong, J. Vonk, H. Boezen, C. V. Diemen

{"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}

引用次数: 0

Genomic analysis of CC16 as a biomarker for COPD CC16作为COPD生物标志物的基因组分析

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 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

引用次数: 0

Exome sequencing reveals immune genes as susceptibility modifiers in a1-antitrypsin deficiency 外显子组测序显示免疫基因是a1-抗胰蛋白酶缺乏症的易感性修饰因子

IF 1.7 4区医学

Genes and Environment Pub Date : 2018-09-15 DOI: 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

引用次数: 0