Study of common and rare genetic variants in respiratory health: the UK Biobank Lung Exome Evaluation (UK BiLEVE) consoertium

呼吸系统健康中常见和罕见遗传变异的研究：英国生物银行肺外显子组评估 (UK BiLEVE) 联盟

• 批准号: MC_PC_12010
• 负责人: Ian Hall
• 金额: $ 413.48万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_12010
• 关键词: Study; common; rare; genetic; variants

Lung function is an important indicator of respiratory health and moratlity. Measures of lung function show irreversible airway ostruction in chronic obstructive pulmonary disease (COPD), a progressive condition affecting 900,000 people in the UK. Smoking is a strong risk factor for COPD but not all smokers are equaly susceptible. Genetic approaches to understanding the mechanisms underlying the maintenance of good lung others, aim to reveal previously unknown molecular targets for drug development and to facilitiate stratified approaches to treatment and care. This project aims to detect rare genetic variants associated with lung function. Once discovered, such variants tend to exert a large effect on disease risk and provide a means to translate findings from genetic studies of lung function to clinical relevant research and development. The proposed study leverages the power of Uk Biobank and respiratory genomics to advance understanding of lung function and COPD. This project will use a customised respiratory exome chip in 50,000 UK Biobank participants, selected according to their smoking history and lung function status at baseline. This project therefore requires teh use of data (spirometry, smoking and other lifestyle factors) and DNA samples.

肺功能是反映呼吸健康和呼吸暂停的重要指标。肺功能测量显示，慢性阻塞性肺疾病(COPD)的呼吸道结构不可逆转，这是一种进行性疾病，在英国影响着90万人。吸烟是慢性阻塞性肺疾病的强烈危险因素，但并不是所有的吸烟者都同样容易受到影响。通过遗传学方法了解维持良好肺功能的机制，旨在揭示以前未知的药物开发的分子靶点，并使治疗和护理的分层方法简便易行。该项目旨在检测与肺功能相关的罕见基因变异。一旦被发现，这些变异往往会对疾病风险产生很大影响，并提供一种手段，将肺功能的基因研究成果转化为临床相关研究和开发。这项拟议的研究利用英国生物库和呼吸基因组学的力量来促进对肺功能和COPD的了解。该项目将在50,000名英国生物库参与者中使用定制的呼吸外显子组芯片，根据他们的吸烟史和基线时的肺功能状况进行选择。因此，该项目需要使用数据(肺活量、吸烟和其他生活方式因素)和DNA样本。

项目成果

Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.

• DOI: 10.1016/s2213-2600(17)30387-9
• 发表时间: 2017-11
• 期刊: The Lancet. Respiratory medicine
• 作者: Allen RJ;Porte J;Braybrooke R;Flores C;Fingerlin TE;Oldham JM;Guillen-Guio B;Ma SF;Okamoto T;John AE;Obeidat M;Yang IV;Henry A;Hubbard RB;Navaratnam V;Saini G;Thompson N;Booth HL;Hart SP;Hill MR;Hirani N;Maher TM;McAnulty RJ;Millar AB;Molyneaux PL;Parfrey H;Rassl DM;Whyte MKB;Fahy WA;Marshall RP;Oballa E;Bossé Y;Nickle DC;Sin DD;Timens W;Shrine N;Sayers I;Hall IP;Noth I;Schwartz DA;Tobin MD;Wain LV;Jenkins RG
• 通讯作者: Jenkins RG

Targeted Sequencing of Lung Function Loci in Chronic Obstructive Pulmonary Disease Cases and Controls.

在慢性阻塞性肺部疾病病例和对照中，肺功能基因座的靶向测序。

• DOI: 10.1371/journal.pone.0170222
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Artigas MS;Wain LV;Shrine N;McKeever TM;UK BiLEVE;Sayers I;Hall IP;Tobin MD
• 通讯作者: Tobin MD

Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.

• DOI: 10.1093/ije/dyw318
• 发表时间: 2017-06-01
• 期刊: International journal of epidemiology
• 影响因子: 7.7
• 作者: Aschard H;Tobin MD;Hancock DB;Skurnik D;Sood A;James A;Vernon Smith A;Manichaikul AW;Campbell A;Prins BP;Hayward C;Loth DW;Porteous DJ;Strachan DP;Zeggini E;O'Connor GT;Brusselle GG;Boezen HM;Schulz H;Deary IJ;Hall IP;Rudan I;Kaprio J;Wilson JF;Wilk JB;Huffman JE;Hua Zhao J;de Jong K;Lyytikäinen LP;Wain LV;Jarvelin MR;Kähönen M;Fornage M;Polasek O;Cassano PA;Barr RG;Rawal R;Harris SE;Gharib SA;Enroth S;Heckbert SR;Lehtimäki T;Gyllensten U;Understanding Society Scientific Group;Jackson VE;Gudnason V;Tang W;Dupuis J;Soler Artigas M;Joshi AD;London SJ;Kraft P
• 通讯作者: Kraft P

Human CCL3L1 copy number variation, gene expression, and the role of the CCL3L1-CCR5 axis in lung function

人 CCL3L1 拷贝数变异、基因表达以及 CCL3L1-CCR5 轴在肺功能中的作用

• DOI: 10.12688/wellcomeopenres.13902.1
• 发表时间: 2018
• 期刊: Wellcome Open Research
• 作者: Adewoye A