Genome-wide association study identifies five loci associated with lung function

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, Ines Barroso, Ruth J. F. LoosNicholas 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 Glaeser, Georg Homuth, Henry Voelzke, Massimo Mangino, Nicole Soranzo, Tim D. Spector, Ozren Polasek, Igor Rudan, Alan F. Wright, Markku Heliovaara, Samuli Ripatti, Anneli Pouta, Cathy Jackson, Wellcome Trust Case Control Consor, NSHD Resp Study Team

Research output: Contribution to journalArticlepeer-review

472 Citations (Scopus)


Pulmonary 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 (FEV1) and the ratio of FEV1 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 <= 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/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.

Original languageEnglish
Pages (from-to)36-51
Number of pages10
JournalNature Genetics
Issue number1
Early online date13 Dec 2009
Publication statusPublished - Jan 2010




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