Opportunities and Challenges in the Genetics of COPD 2010: An International COPD Genetics Conference Report

REFERENCES

• Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007; 176:532–555.
   PubMed Web of Science ®Google Scholar
• Burrows B, Knudson RJ, Cline MG, Lebowitz MD. Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 1977; 115:195–205.
   PubMed Web of Science ®Google Scholar
• Fletcher C, Peto R, Tinker C, Speizer FE. Factors related to the development of airflow obstruction. In: The natural history of chronic bronchitis and emphysema. Oxford: Oxford University Press; 1976:70–105.
   Google Scholar
• Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O'Donnell WJ, Reilly JJ, Ginns L, Mentzer S, Wain J, Speizer FE. Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease: Risk to relatives for airflow obstruction and chronic bronchitis. Amer J Respir Crit Care Med 1998; 157:1770–1778.
   PubMed Web of Science ®Google Scholar
• McCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA. Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med 2001; 164:1419–1424.
   PubMed Web of Science ®Google Scholar
• Regalado J, Perez-Padilla R, Sansores R, Paramo Ramirez JI, Brauer M, Pare P, Vedal S. The effect of biomass burning on respiratory symptoms and lung function in rural Mexican women. Am J Respir Crit Care Med 2006; 174:901–905.
   PubMed Web of Science ®Google Scholar
• Castaldi PJ, Cho MH, Cohn M, Langerman F, Moran S, Tarragona N, Moukhachen H, Venugopal R, Hasimja D, Kao E, Wallace B, Hersh CP, Bagade S, Bertram L, Silverman EK, Trikalinos TA. The COPD genetic association compendium: a comprehensive online database of COPD genetic associations. Hum Mol Genet 2010; 19:526–534.
   PubMed Web of Science ®Google Scholar
• Smolonska J, Wijmenga C, Postma DS, Boezen HM. Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years’ research. Am J Respir Crit Care Med 2009; 180:618–631.
   PubMed Web of Science ®Google Scholar
• Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 2009; 4:435–459.
   PubMed Web of Science ®Google Scholar
• Kim WJ, Hoffman E, Reilly J, Hersh C, Demeo D, Washko G, Silverman EK. Association of COPD candidate genes with CT emphysema and airway phenotypes in severe COPD. European Respiratory Journal 2011; 37:39–43.
   PubMed Web of Science ®Google Scholar
• Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, Macnee W, Make BJ, Rabe KF, Rennard SI, Sciurba FC, Silverman EK, Vestbo J, Washko GR, Wouters EF, Martinez FJ. Chronic obstructive pulmonary disease phenotypes: The future of COPD. Am J Respir Crit Care Med 2010; 182:598–604.
   PubMed Web of Science ®Google Scholar
• Pillai SG, Ge D, Zhu G, Kong X, Shianna KV, Need AC, Feng S, Hersh CP, Bakke P, Gulsvik A, Ruppert A, Lodrup Carlsen KC, Roses A, Anderson W, Rennard SI, Lomas DA, Silverman EK, Goldstein DB. A genome-wide association study in chronic obstructive pulmonary disease (COPD): Identification of two major susceptibility loci. PLoS Genet 2009; 5:e1000421.
   PubMed Web of Science ®Google Scholar
• DeMeo DL, Mariani T, Bhattacharya S, Srisuma S, Lange C, Litonjua A, Bueno R, Pillai SG, Lomas DA, Sparrow D, Shapiro SD, Criner GJ, Kim HP, Chen Z, Choi AM, Reilly J, Silverman EK. Integration of genomic and genetic approaches implicates IREB2 as a COPD susceptibility gene. Am J Hum Genet 2009; 85:493–502.
   PubMed Web of Science ®Google Scholar
• Wilk JB, Chen TH, Gottlieb DJ, Walter RE, Nagle MW, Brandler BJ, Myers RH, Borecki IB, Silverman EK, Weiss ST, O'Connor GT. A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet 2009; 5:e1000429.
   PubMed Web of Science ®Google Scholar
• Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, Franceschini N, van Durme YM, Chen TH, Barr RG, Schabath MB, Couper DJ, Brusselle GG, Psaty BM, van Duijn CM, Rotter JI, Uitterlinden AG, Hofman A, Punjabi NM, Rivadeneira F, Morrison AC, Enright PL, North KE, Heckbert SR, Lumley T, Stricker BH, O'Connor GT, London SJ. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet 2010; 42:45–52.
   PubMed Web of Science ®Google Scholar
• Repapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M, Zhao JH, Ramasamy A, Zhai G, Vitart V, Huffman JE, Igl W, Albrecht E, Deloukas P, Henderson J, Granell R, McArdle WL, Rudnicka AR, Barroso I, Loos RJ, Wareham NJ, Mustelin L, Rantanen T, Surakka I, Imboden M, Wichmann HE, Grkovic I, Jankovic S, Zgaga L, Hartikainen AL, Peltonen L, Gyllensten U, Johansson A, Zaboli G, Campbell H, Wild SH, Wilson JF, Glaser S, Homuth G, Volzke H, Mangino M, Soranzo N, Spector TD, Polasek O, Rudan I, Wright AF, Heliovaara M, Ripatti S, Pouta A, Naluai AT, Olin AC, Toren K, Cooper MN, James AL, Palmer LJ, Hingorani AD, Wannamethee SG, Whincup PH, Smith GD, Ebrahim S, McKeever TM, Pavord ID, MacLeod AK, Morris AD, Porteous DJ, Cooper C, Dennison E, Shaheen S, Karrasch S, Schnabel E, Schulz H, Grallert H, Bouatia-Naji N, Delplanque J, Froguel P, Blakey JD, Britton JR, Morris RW, Holloway JW, Lawlor DA, Hui J, Nyberg F, Jarvelin MR, Jackson C, Kahonen M, Kaprio J, Probst-Hensch NM, Koch B, Hayward C, Evans DM, Elliott P, Strachan DP, Hall IP, Tobin MD. Genome-wide association study identifies five loci associated with lung function. Nat Genet 2010; 42:36–44.
   PubMed Web of Science ®Google Scholar
• Cho MH, Boutaoui N, Klanderman BJ, Sylvia JS, Ziniti JP, Hersh CP, DeMeo DL, Hunninghake GM, Litonjua A, Sparrow D, Lange C, Won S, Murphy J, Beaty T, Regan EA, Make B, Hokanson JE, Crapo JD, Kong XQ, Anderson WH, Tal-Singer R, Lomas DA, Bakke P, Gulsvik A, Pillai SG, Silverman EK. Variants in FAM13A are associated with chronic obstructive pulmonary disease. Nature Genetics 2010; 42:200–202.
   PubMed Web of Science ®Google Scholar
• Young RP, Hopkins RJ, Hay BA, Epton MJ, Black PN, Gamble GD. Lung cancer gene associated with COPD: triple whammy or possible confounding effect? Eur Respir J 2008; 32:1158–1164.
   PubMed Web of Science ®Google Scholar
• Lambrechts D, Buysschaert I, Zanen P, Coolen J, Lays N, Cuppens H, Groen HJ, Dewever W, van Klaveren RJ, Verschakelen J, Wijmenga C, Postma DS, Decramer M, Janssens W. The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema. Am J Respir Crit Care Med 2010; 181:486–493.
   PubMed Web of Science ®Google Scholar
• Young RP, Whittington CF, Hopkins RJ, Hay BA, Epton MJ, Black PN, Gamble GD. Chromosome 4q31 locus in COPD is also associated with lung cancer. Eur Respir J 2010; 36:1375–1382.
   PubMed Web of Science ®Google Scholar
• Van Durme YM, Eijgelsheim M, Joos GF, Hofman A, Uitterlinden AG, Brusselle GG, Stricker BH. Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study. Eur Respir J 2010; 36:89–95.
   PubMed Web of Science ®Google Scholar
• Young RP, Hopkins RJ, Hay BA, Whittington CF, Epton MJ, Gamble GD. FAM13A locus in COPD is independently associated with lung cancer–evidence of a molecular genetic link between COPD and lung cancer. The Application of Clinical Genetics 2011; 4:1–10.
   Google Scholar
• Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, Segre AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Bengtsson Bostrom K, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jorgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proenca C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparso T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet-Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Altshuler D, Boehnke M, McCarthy MI. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 2010; 42:579–589.
   PubMed Web of Science ®Google Scholar
• Truong T, Hung RJ, Amos CI, Wu X, Bickeboller H, Rosenberger A, Sauter W, Illig T, Wichmann HE, Risch A, Dienemann H, Kaaks R, Yang P, Jiang R, Wiencke JK, Wrensch M, Hansen H, Kelsey KT, Matsuo K, Tajima K, Schwartz AG, Wenzlaff A, Seow A, Ying C, Staratschek-Jox A, Nurnberg P, Stoelben E, Wolf J, Lazarus P, Muscat JE, Gallagher CJ, Zienolddiny S, Haugen A, Van Der Heijden HF, Kiemeney LA, Isla D, Mayordomo JI, Rafnar T, Stefansson K, Zhang ZF, Chang SC, Kim JH, Hong YC, Duell EJ, Andrew AS, Lejbkowicz F, Rennert G, Muller H, Brenner H, Le Marchand L, Benhamou S, Bouchardy C, Teare MD, Xue X, McLaughlin J, Liu G, McKay JD, Brennan P, Spitz MR. Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J Natl Cancer Inst 2010; 102:959–971.
   Google Scholar
• Truong T, Sauter W, McKay JD, Hosgood HD, 3rd, Gallagher C, Amos CI, Spitz M, Muscat J, Lazarus P, Illig T, Wichmann HE, Bickeboller H, Risch A, Dienemann H, Zhang ZF, Naeim BP, Yang P, Zienolddiny S, Haugen A, Le Marchand L, Hong YC, Kim JH, Duell EJ, Andrew AS, Kiyohara C, Shen H, Matsuo K, Suzuki T, Seow A, Ng DP, Lan Q, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Constantinescu V, Bencko V, Foretova L, Janout V, Caporaso NE, Albanes D, Thun M, Landi MT, Trubicka J, Lener M, Lubinski J, Wang Y, Chabrier A, Boffetta P, Brennan P, Hung RJ. International Lung Cancer Consortium: coordinated association study of 10 potential lung cancer susceptibility variants. Carcinogenesis 2010; 31:625–633.
   PubMed Web of Science ®Google Scholar
• Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, Sulem P, Rafnar T, Esko T, Walter S, Gieger C, Rawal R, Mangino M, Prokopenko I, Magi R, Keskitalo K, Gudjonsdottir IH, Gretarsdottir S, Stefansson H, Thompson JR, Aulchenko YS, Nelis M, Aben KK, den Heijer M, Dirksen A, Ashraf H, Soranzo N, Valdes AM, Steves C, Uitterlinden AG, Hofman A, Tonjes A, Kovacs P, Hottenga JJ, Willemsen G, Vogelzangs N, Doring A, Dahmen N, Nitz B, Pergadia ML, Saez B, De Diego V, Lezcano V, Garcia-Prats MD, Ripatti S, Perola M, Kettunen J, Hartikainen AL, Pouta A, Laitinen J, Isohanni M, Huei-Yi S, Allen M, Krestyaninova M, Hall AS, Jones GT, van Rij AM, Mueller T, Dieplinger B, Haltmayer M, Jonsson S, Matthiasson SE, Oskarsson H, Tyrfingsson T, Kiemeney LA, Mayordomo JI, Lindholt JS, Pedersen JH, Franklin WA, Wolf H, Montgomery GW, Heath AC, Martin NG, Madden PA, Giegling I, Rujescu D, Jarvelin MR, Salomaa V, Stumvoll M, Spector TD, Wichmann HE, Metspalu A, Samani NJ, Penninx BW, Oostra BA, Boomsma DI, Tiemeier H, van Duijn CM, Kaprio J, Gulcher JR, McCarthy MI, Peltonen L, Thorsteinsdottir U, Stefansson K. Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 2010; 42:448–453.
   PubMed Web of Science ®Google Scholar
• Hunninghake GM, Cho MH, Tesfaigzi Y, Soto-Quiros ME, Avila L, Lasky-Su J, Stidley C, Melen E, Soderhall C, Hallberg J, Kull I, Kere J, Svartengren M, Pershagen G, Wickman M, Lange C, Demeo DL, Hersh CP, Klanderman BJ, Raby BA, Sparrow D, Shapiro SD, Silverman EK, Litonjua AA, Weiss ST, Celedon JC. MMP12, lung function, and COPD in high-risk populations. N Engl J Med 2009; 361:2599–2608.
   PubMed Web of Science ®Google Scholar
• Schadt EE. Molecular networks as sensors and drivers of common human diseases. Nature 2009; 461:218–223.
   PubMed Web of Science ®Google Scholar
• Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, Davies J, Ervine A, Poulter L, Pachter L, Moffatt MF, Cookson WO. Disordered microbial communities in asthmatic airways. PLoS One 2010; 5:e8578.
   PubMed Web of Science ®Google Scholar
• Thornton-Wells TA, Moore JH, Haines JL. Genetics, statistics and human disease: analytical retooling for complexity. Trends Genet 2004; 20:640–647.
   PubMed Web of Science ®Google Scholar
• Wenzel SE. Asthma: Defining of the persistent adult phenotypes. Lancet 2006; 368:804–813.
   PubMed Web of Science ®Google Scholar
• Freimer N, Sabatti C. The human phenome project. Nat Genet 2003; 34:15–21.
   PubMed Web of Science ®Google Scholar
• Molfino NA. Genetics of COPD. Chest 2004; 125:1929–1940.
   PubMed Web of Science ®Google Scholar
• Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, Pinto Plata V, Cabral HJ. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004; 350:1005–1012.
   PubMed Web of Science ®Google Scholar
• Agusti AG. COPD, a multicomponent disease: implications for management. Respir Med 2005; 99:670–682.
   PubMed Web of Science ®Google Scholar
• Hargreave FE, Parameswaran K. Asthma, COPD and bronchitis are just components of airway disease. Eur Respir J 2006; 28:264–267.
   PubMed Web of Science ®Google Scholar
• Wardlaw AJ, Silverman M, Siva R, Pavord ID, Green R. Multi-dimensional phenotyping: towards a new taxonomy for airway disease. Clin Exp Allergy 2005; 35:1254–1262.
   PubMed Web of Science ®Google Scholar
• Vestbo J, Hogg JC. Convergence of the epidemiology and pathology of COPD. Thorax 2006; 61:86–88.
   PubMed Web of Science ®Google Scholar
• Friedlander AL, Lynch D, Dyar LA, Bowler RP. Phenotypes of chronic obstructive pulmonary disease. COPD 2007; 4:355–384.
   PubMedGoogle Scholar
• Sevenoaks MJ, Stockley RA. Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity–a common inflammatory phenotype? Respir Res 2006; 7:70.
   PubMed Web of Science ®Google Scholar
• Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet 1981; 1:681–686.
   PubMed Web of Science ®Google Scholar
• Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980; 93:391–398.
   PubMed Web of Science ®Google Scholar
• Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, Weinmann G, Wood DE. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003; 348:2059–2073.
   PubMed Web of Science ®Google Scholar
• Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009; 374:685–694.
   PubMed Web of Science ®Google Scholar
• Hayhurst MD, MacNee W, Flenley DC, Wright D, McLean A, Lamb D, Wightman AJ, Best J. Diagnosis of pulmonary emphysema by computerised tomography. Lancet 1984; 2:320–322.
   PubMed Web of Science ®Google Scholar
• Nakano Y, Muro S, Sakai H, Hirai T, Chin K, Tsukino M, Nishimura K, Itoh H, Pare PD, Hogg JC, Mishima M. Computed tomographic measurements of airway dimensions and emphysema in smokers. Correlation with lung function. Am J Respir Crit Care Med 2000; 162:1102–1108.
   PubMed Web of Science ®Google Scholar
• Siddiqui S, Gupta S, Cruse G, Haldar P, Entwisle J, McDonald S, Whithers PJ, Hainsworth SV, Coxson HO, Brightling C. Airway wall geometry in asthma and nonasthmatic eosinophilic bronchitis. Allergy 2009; 64:951–958.
   PubMed Web of Science ®Google Scholar
• Nakano Y, Wong JC, de Jong PA, Buzatu L, Nagao T, Coxson HO, Elliott WM, Hogg JC, Pare PD. The prediction of small airway dimensions using computed tomography. Am J Respir Crit Care Med 2005; 171:142–146.
   PubMed Web of Science ®Google Scholar
• Piitulainen E, Eriksson S. Decline in FEV1 related to smoking status in individuals with severe alpha1-antitrypsin deficiency (PiZZ). Eur Respir J 1999; 13:247–251.
   PubMed Web of Science ®Google Scholar
• Hubert HB, Fabsitz RR, Feinleib M, Gwinn C. Genetic and environmental influences on pulmonary function in adult twins. Am Rev Respir Dis 1982; 125:409–415.
   PubMed Web of Science ®Google Scholar
• Dockery DW, Speizer FE, Ferris BG, Jr., Ware JH, Louis TA, Spiro A, III. Cumulative and reversible effects of lifetime smoking on simple tests of lung function in adults. Am Rev Respir Dis 1988; 137:286–292.
   PubMed Web of Science ®Google Scholar
• Givelber RJ, Couropmitree NN, Gottlieb DJ, Evans JC, Levy D, Myers RH, O'Connor GT. Segregation analysis of pulmonary function among families in the Framingham Study. Amer J Respir Crit Care Med 1998; 157:1445–1451.
   PubMed Web of Science ®Google Scholar
• Young RP, Hopkins R, Eaton TE. Forced expiratory volume in one second: not just a lung function test but a marker of premature death from all causes. Eur Respir J 2007; 30:616–622.
   PubMed Web of Science ®Google Scholar
• McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, Hirschhorn JN. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008; 9:356–369.
   PubMed Web of Science ®Google Scholar
• Lin DY, Zeng D. Meta-analysis of genome-wide association studies: no efficiency gain in using individual participant data. Genet Epidemiol 2010; 34:60–66.
   PubMed Web of Science ®Google Scholar
• Smolonska J, Wijmenga C, van Ginneken B, de Hoop B, Dijkstra A, Platteel M, Postma DS, Ouderk M, Mali W, Lammers JW, Groen HJ, Zanen P, Boezen HM. COPACETIC, a genome-wide association study on chronic obstructive pulmonary disease (COPD). European Respiratory Society Congress Abstract Book (Barcelona) 2010: 1567.
   Google Scholar
• Regan EA, Hokanson JE, Murphy JR, Make B, Lynch DA, Beaty TH, Curran-Everett D, Silverman EK, Crapo JD. Genetic epidemiology of COPD (COPDGene) study design. COPD 2010; 7:32–43.
   PubMedGoogle Scholar
• Vestbo J, Anderson W, Coxson HO, Crim C, Dawber F, Edwards L, Hagan G, Knobil K, Lomas DA, MacNee W, Silverman EK, Tal-Singer R. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). Eur Respir J 2008; 31:869–873.
   PubMed Web of Science ®Google Scholar
• Chappell S, Daly L, Morgan K, Guetta Baranes T, Roca J, Rabinovich R, Millar A, Donnelly SC, Keatings V, MacNee W, Stolk J, Hiemstra P, Miniati M, Monti S, O'Connor CM, Kalsheker N. Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease. Hum Mutat 2006; 27:103–109.
   PubMed Web of Science ®Google Scholar
• Makita H, Nasuhara Y, Nagai K, Ito Y, Hasegawa M, Betsuyaku T, Onodera Y, Hizawa N, Nishimura M. Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease. Thorax 2007; 62:932–937.
   PubMed Web of Science ®Google Scholar
• Siebeling L, ter Riet G, Van Der Wal WM, Geskus RB, Zoller M, Muggensturm P, Joleska I, Puhan MA. ICE COLD ERIC—International collaborative effort on chronic obstructive lung disease: exacerbation risk index cohorts–study protocol for an international COPD cohort study. BMC Pulm Med 2009; 9:15.
   PubMedGoogle Scholar
• Kim WJ, Oh YM, Sung J, Lee YK, Seo JB, Kim N, Kim TH, Huh JW, Lee JH, Kim EK, Lee SM, Lee S, Lim SY, Shin TR, Yoon HI, Kwon SY, Lee SD. CT scanning-based phenotypes vary with ADRB2 polymorphisms in chronic obstructive pulmonary disease. Respir Med 2009; 103:98–103.
   PubMed Web of Science ®Google Scholar
• Connett JE, Kusek JW, Bailey WC, O'Hara P, Wu M. Design of the Lung Health Study: a randomized clinical trial of early intervention for chronic obstructive pulmonary disease. Controlled Clinical Trials 1993; 14:3S–19S.
   PubMedGoogle Scholar
• Garcia-Aymerich J, Gomez FP, Anto JM. [Phenotypic characterization and course of chronic obstructive pulmonary disease in the PAC-COPD Study: design and methods]. Arch Bronconeumol 2009; 45:4–11.
   PubMed Web of Science ®Google Scholar
• Sadeghnejad A, Meyers DA, Bottai M, Sterling DA, Bleecker ER, Ohar JA. IL13 promoter polymorphism 1112C/T modulates the adverse effect of tobacco smoking on lung function. Am J Respir Crit Care Med 2007; 176:748–752.
   PubMed Web of Science ®Google Scholar
• Mesia-Vela S, Yeh CC, Austin JH, Dounel M, Powell CA, Reeves A, Santella RM, Stevenson L, Yankelevitz D, Barr RG. Plasma carbonyls do not correlate with lung function or computed tomography measures of lung density in older smokers. Biomarkers 2008; 13:422–434.
   PubMed Web of Science ®Google Scholar
• Stolk RP, Rosmalen JG, Postma DS, de Boer RA, Navis G, Slaets JP, Ormel J, Wolffenbuttel BH. Universal risk factors for multifactorial diseases: LifeLines: a three-generation population-based study. Eur J Epidemiol 2008; 23:67–74.
   PubMed Web of Science ®Google Scholar
• Sood A, Stidley CA, Picchi MA, Celedon JC, Gilliland F, Crowell RE, Belinsky SA, Tesfaigzi Y. Difference in airflow obstruction between Hispanic and non-Hispanic White female smokers. COPD 2008; 5:274–281.
   PubMedGoogle Scholar
• Barr RG, Bluemke DA, Ahmed FS, Carr JJ, Enright PL, Hoffman EA, Jiang R, Kawut SM, Kronmal RA, Lima JA, Shahar E, Smith LJ, Watson KE. Percent emphysema, airflow obstruction, and impaired left ventricular filling. N Engl J Med 2010; 362:217–227.
   PubMed Web of Science ®Google Scholar
• van Diemen CC, Postma DS, Vonk JM, Bruinenberg M, Schouten JP, Boezen HM. A disintegrin and metalloprotease 33 polymorphisms and lung function decline in the general population. Am J Respir Crit Care Med 2005; 172:329–333.
   PubMed Web of Science ®Google Scholar
• Patel BD, Coxson HO, Pillai SG, Agusti AG, Calverley PM, Donner CF, Make BJ, Muller NL, Rennard SI, Vestbo J, Wouters EF, Hiorns MP, Nakano Y, Camp PG, Nasute Fauerbach PV, Screaton NJ, Campbell EJ, Anderson WH, Pare PD, Levy RD, Lake SL, Silverman EK, Lomas DA. Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008; 178:500–505.
   PubMed Web of Science ®Google Scholar
• Musunuru K, Lettre G, Young T, Farlow DN, Pirruccello JP, Ejebe KG, Keating BJ, Yang Q, Chen MH, Lapchyk N, Crenshaw A, Ziaugra L, Rachupka A, Benjamin EJ, Cupples LA, Fornage M, Fox ER, Heckbert SR, Hirschhorn JN, Newton-Cheh C, Nizzari MM, Paltoo DN, Papanicolaou GJ, Patel SR, Psaty BM, Rader DJ, Redline S, Rich SS, Rotter JI, Taylor HA, Jr., Tracy RP, Vasan RS, Wilson JG, Kathiresan S, Fabsitz RR, Boerwinkle E, Gabriel SB. Candidate gene association resource (CARe): design, methods, and proof of concept. Circ Cardiovasc Genet 2010; 3:267–275.
   PubMed Web of Science ®Google Scholar