Meta-analysis of exome array data identifies six novel genetic loci for lung function
Authors: Jackson Victoria E. , Latourelle Jeanne C. , Wain Louise V. , Smith Albert V. , Grove Megan L. , Bartz Traci M. , Obeidat Ma'en , Province Michael A. , Gao Wei , Qaiser Beenish , Porteous David J. , Cassano Patricia A. , Ahluwalia Tarunveer S. , Grarup Niels , Li Jin , Altmaier Elisabeth , Marten Jonathan , Harris Sarah E. , Manichaikul Ani , Pottinger Tess D. , Li-Gao Ruifang , Lind-Thomsen Allan , Mahajan Anubha , Lahousse Lies , Imboden Medea , Teumer Alexander , Prins Bram , Lyytikäinen Leo-Pekka , Eiriksdottir Gudny , Franceschini Nora , Sitlani Colleen M. , Brody Jennifer A. , Bossé Yohan , Timens Wim , Kraja Aldi , Loukola Anu , Tang Wenbo , Liu Yongmei , Bork-Jensen Jette , Justesen Johanne M. , Linneberg Allan , Lange Leslie A. , Rawal Rajesh , Karrasch Stefan , Huffman Jennifer E. , Smith Blair H. , Davies Gail , Burkart Kristin M. , Mychaleckyj Josyf C. , Bonten Tobias N. , Enroth Stefan , Lind Lars , Brusselle Guy G. , Kumar Ashish , Stubbe Beate ,   Understanding Society Scientific Group, Kähönen Mika , Wyss Annah B. , Psaty Bruce M. , Heckbert Susan R. , Hao Ke , Rantanen Taina , Kritchevsky Stephen B. , Lohman Kurt , Skaaby Tea , Pisinger Charlotta , Hansen Torben , Schulz Holger , Polasek Ozren , Campbell Archie I. , Starr John M. , Rich Stephen S. , Mook-Kanamori Dennis O. , Johansson Åsa , Ingelsson Erik , Uitterlinden André G. , Weiss Stefan , Raitakari Olli T. , Gudnason Vilmundur , North Kari E. , Gharib Sina A. , Sin Don D. , Taylor Kent D. , O'Connor George T. , Kaprio Jaakko , Harris Tamara B. , Pederson Oluf , Vestergaard Henrik , Wilson James G. , Strauch Konstantin , Hayward Caroline , Kerr Shona M. , Deary Ian J. , Barr R. Graham , de Mutsert Renée , Gyllensten Ulf , Morris Andrew P. , Ikram M. Arfan , Probst-Hensch Nicole , Gläser Sven , Zeggini Eleftheria , Lehtimäki Terho , Strachan David P. , Dupuis Josée , Morrison Alanna C. , Hall Ian P. , Tobin Martin D. , London Stephanie J. 
Published: August 2018

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease.

Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals.

Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU.

Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.