TY - JOUR
T1 - Meta-analysis of exome array data identifies six novel genetic loci for lung function.
AU - Understanding Society Scientific group
AU - Jackson, Victoria E.
AU - Latourelle, Jeanne C.
AU - Wain, Louise V.
AU - Smith, Albert V.
AU - Grove, Megan L.
AU - Bartz, Traci M.
AU - Obeidat, Ma’En
AU - Province, Michael A.
AU - Gao, Wei
AU - Qaiser, Beenish
AU - Porteous, David J.
AU - Cassano, Patricia A.
AU - Ahluwalia, Tarunveer S.
AU - Grarup, Niels
AU - Li, Jin
AU - Altmaier, Elisabeth
AU - Marten, Jonathan
AU - Harris, Sarah E.
AU - Manichaikul, Ani
AU - Pottinger, Tess D.
AU - Li-Gao, Ruifang
AU - Lind-Thomsen, Allan
AU - Mahajan, Anubha
AU - Lahousse, Lies
AU - Imboden, Medea
AU - Teumer, Alexander
AU - Prins, Bram
AU - Lyytikäinen, Leo Pekka
AU - Eiriksdottir, Gudny
AU - Franceschini, Nora
AU - Sitlani, Colleen M.
AU - Brody, Jennifer A.
AU - Bossé, Yohan
AU - Timens, Wim
AU - Kraja, Aldi
AU - Loukola, Anu
AU - Tang, Wenbo
AU - Liu, Yongmei
AU - Bork-Jensen, Jette
AU - Justesen, Johanne M.
AU - Linneberg, Allan
AU - Lange, Leslie A.
AU - Rawal, Rajesh
AU - Karrasch, Stefan
AU - Huffman, Jennifer E.
AU - Smith, Blair H.
AU - Davies, Gail
AU - Burkart, Kristin M.
AU - Mychaleckyj, Josyf C.
AU - Bonten, Tobias N.
N1 - Publisher Copyright:
© 2018 Jackson VE et al
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - COPD
KW - Exome array
KW - GWAS
KW - Lung function
KW - Respiratory
UR - http://www.scopus.com/inward/record.url?scp=85062102402&partnerID=8YFLogxK
U2 - 10.12688/wellcomeopenres.12583.1
DO - 10.12688/wellcomeopenres.12583.1
M3 - Article
AN - SCOPUS:85062102402
SN - 2398-502X
VL - 3
JO - Wellcome Open Research
JF - Wellcome Open Research
M1 - 4
ER -