Discovery of genome-wide SNP associations for lung function

发现全基因组 SNP 与肺功能的关联

• 批准号: MR/N011317/1
• 负责人: Martin Tobin
• 金额: $ 47.89万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN011317%2F1
• 关键词: Discovery; genome; wide; SNP; associations

Chronic obstructive pulmonary disease (COPD) is a debilitating and incurable lung disease that affects 900,000 people in the UK with one person dying from COPD every 20 minutes in England. It is well known that smoking can cause lung disease including COPD. However, not all smokers are equally at risk of developing COPD, and not all people who develop COPD are smokers. Genetics also plays a role in lung function and in our risk of developing lung diseases. Identifying which genes affect how well our lungs work tells us more about the biology underlying lung health and can lead to development of new treatments for COPD. By studying large groups of individuals, for whom we had both measurements of lung capacity and measurements of how much they vary from each other genetically (genetic variation), we have so far identified 52 regions of our DNA where genetic variation affects lung health. However, we know that there are more regions to be identified, and we need larger and more sophisticated studies to achieve this. Identification of more regions will tell us more about which biological mechanisms are important in lung disease and reveal more about potential approaches to therapy.The aim of this research project is to discover further regions of the genome associated with lung function using data from more than 600,000 individuals. The approaches used to measure genetic variation have improved rapidly in recent times enabling us to simultaneously analyse more genes and other regions of DNA than in previous studies. Combining this with very large sample sizes will enable us to increase the number of regions identified. Achievement of this aim will tell us more about lung health and disease and could lead to new drugs and treatment which improve the lives of individuals with COPD, or prevent COPD from developing.

慢性阻塞性肺疾病(COPD)是一种使人衰弱且无法治愈的肺部疾病，在英国，每20分钟就有一人死于慢性阻塞性肺疾病。众所周知，吸烟会导致包括慢性阻塞性肺病在内的肺部疾病。然而，并不是所有的吸烟者都有同样的风险患上COPD，也不是所有的COPD患者都是吸烟者。基因也在肺功能和我们患肺部疾病的风险中发挥作用。识别哪些基因会影响我们肺部的工作状况，可以让我们更多地了解肺健康背后的生物学基础，并有助于开发COPD的新疗法。通过对大群个体的研究，我们既测量了他们的肺活量，也测量了他们彼此在遗传上的差异(遗传变异)，到目前为止，我们已经确定了我们DNA中52个基因变异影响肺部健康的区域。然而，我们知道有更多的地区需要确定，我们需要更大、更复杂的研究来实现这一点。识别更多的区域将告诉我们更多关于哪些生物机制在肺部疾病中起重要作用，并揭示更多潜在的治疗方法。这项研究项目的目的是利用来自60多万人的数据来发现更多与肺功能相关的基因组区域。近年来，用于测量遗传变异的方法得到了迅速改进，使我们能够同时分析比以前研究中更多的基因和DNA的其他区域。将这一点与非常大的样本量结合起来，将使我们能够增加确定的区域数量。这一目标的实现将使我们了解更多关于肺部健康和疾病的信息，并可能导致新的药物和治疗方法，改善COPD患者的生活，或防止COPD的发展。

项目成果

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

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

• DOI: 10.1038/s41380-018-0313-0
• 发表时间: 2020-10
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Erzurumluoglu AM;Liu M;Jackson VE;Barnes DR;Datta G;Melbourne CA;Young R;Batini C;Surendran P;Jiang T;Adnan SD;Afaq S;Agrawal A;Altmaier E;Antoniou AC;Asselbergs FW;Baumbach C;Bierut L;Bertelsen S;Boehnke M;Bots ML;Brazel DM;Chambers JC;Chang-Claude J;Chen C;Corley J;Chou YL;David SP;de Boer RA;de Leeuw CA;Dennis JG;Dominiczak AF;Dunning AM;Easton DF;Eaton C;Elliott P;Evangelou E;Faul JD;Foroud T;Goate A;Gong J;Grabe HJ;Haessler J;Haiman C;Hallmans G;Hammerschlag AR;Harris SE;Hattersley A;Heath A;Hsu C;Iacono WG;Kanoni S;Kapoor M;Kaprio J;Kardia SL;Karpe F;Kontto J;Kooner JS;Kooperberg C;Kuulasmaa K;Laakso M;Lai D;Langenberg C;Le N;Lettre G;Loukola A;Luan J;Madden PAF;Mangino M;Marioni RE;Marouli E;Marten J;Martin NG;McGue M;Michailidou K;Mihailov E;Moayyeri A;Moitry M;Müller-Nurasyid M;Naheed A;Nauck M;Neville MJ;Nielsen SF;North K;Perola M;Pharoah PDP;Pistis G;Polderman TJ;Posthuma D;Poulter N;Qaiser B;Rasheed A;Reiner A;Renström F;Rice J;Rohde R;Rolandsson O;Samani NJ;Samuel M;Schlessinger D;Scholte SH;Scott RA;Sever P;Shao Y;Shrine N;Smith JA;Starr JM;Stirrups K;Stram D;Stringham HM;Tachmazidou I;Tardif JC;Thompson DJ;Tindle HA;Tragante V;Trompet S;Turcot V;Tyrrell J;Vaartjes I;van der Leij AR;van der Meer P;Varga TV;Verweij N;Völzke H;Wareham NJ;Warren HR;Weir DR;Weiss S;Wetherill L;Yaghootkar H;Yavas E;Jiang Y;Chen F;Zhan X;Zhang W;Zhao W;Zhao W;Zhou K;Amouyel P;Blankenberg S;Caulfield MJ;Chowdhury R;Cucca F;Deary IJ;Deloukas P;Di Angelantonio E;Ferrario M;Ferrières J;Franks PW;Frayling TM;Frossard P;Hall IP;Hayward C;Jansson JH;Jukema JW;Kee F;Männistö S;Metspalu A;Munroe PB;Nordestgaard BG;Palmer CNA;Salomaa V;Sattar N;Spector T;Strachan DP;Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ consortium;van der Harst P;Zeggini E;Saleheen D;Butterworth AS;Wain LV;Abecasis GR;Danesh J;Tobin MD;Vrieze S;Liu DJ;Howson JMM
• 通讯作者: Howson JMM

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

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

Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference.

• DOI: 10.1038/s41467-018-03109-y
• 发表时间: 2018-02-19
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Corbin LJ;Tan VY;Hughes DA;Wade KH;Paul DS;Tansey KE;Butcher F;Dudbridge F;Howson JM;Jallow MW;John C;Kingston N;Lindgren CM;O'Donavan M;O'Rahilly S;Owen MJ;Palmer CNA;Pearson ER;Scott RA;van Heel DA;Whittaker J;Frayling T;Tobin MD;Wain LV;Smith GD;Evans DM;Karpe F;McCarthy MI;Danesh J;Franks PW;Timpson NJ
• 通讯作者: Timpson NJ