• Emmanouela Repapi, Ian Sayers, Louise V Wain, Paul R Burton, Toby Johnson, Ma'en Obeidat, Jing Hua Zhao, Adaikalavan Ramasamy, Guangju Zhai, Veronique Vitart, Jennifer E Huffman, Wilmar Igl, Eva Albrecht, Panos Deloukas, John Henderson, Raquel Granell, Wendy L McArdle, Alicja R Rudnicka, Wellcome Trust Case Control Consortium, Inês Barroso, Ruth J F Loos, Nicholas J Wareham, Linda Mustelin, Taina Rantanen, Ida Surakka, Medea Imboden, H Erich Wichmann, Ivica Grkovic, Stipan Jankovic, Lina Zgaga, Anna-Liisa Hartikainen, Leena Peltonen, Ulf Gyllensten, Asa Johansson, Ghazal Zaboli, Harry Campbell, Sarah H Wild, James F Wilson, Sven Gläser, Georg Homuth, Henry Völzke, Massimo Mangino, Nicole Soranzo, Tim D Spector, Ozren Polasek, Igor Rudan, Alan F Wright, Markku Heliövaara, Samuli Ripatti, Anneli Pouta, Asa Torinsson Naluai, Anna-Carin Olin, Kjell Torén, Matthew N Cooper, Alan L James, Lyle J Palmer, Aroon D Hingorani, S Goya Wannamethee, Peter H Whincup, George Davey Smith, Shah Ebrahim, Tricia M McKeever, Ian D Pavord, Andrew K MacLeod, Andrew D Morris, David J Porteous, Cyrus Cooper, Elaine Dennison, Seif Shaheen, Stefan Karrasch, Eva Schnabel, Holger Schulz, Harald Grallert, Nabila Bouatia-Naji, Jérôme Delplanque, Philippe Froguel, John D Blakey, NSHD Respiratory Study Team, John R Britton, Richard W Morris, John W Holloway, Debbie A Lawlor, Jennie Hui, Fredrik Nyberg, Marjo-Riitta Jarvelin, Cathy Jackson, Mika Kähönen, Jaakko Kaprio, Nicole M Probst-Hensch, Beate Koch, Caroline Hayward, David M Evans, Paul Elliott, David P Strachan, Ian P Hall, and Martin D Tobin.
• Departments of Health Sciences and Genetics, Adrian Building, University of Leicester, Leicester, UK.
• Nat. Genet. 2010 Jan 1; 42 (1): 36-44.

AbstractPulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

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