TY - JOUR

T1 - Meta-analysis of exome array data identifies six novel genetic loci for lung function

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 - Lind, Lars

AU - Pisinger, Charlotta

AU - Hansen, Torben

AU - Vestergaard, Henrik

AU - Understanding Society Scientific Group

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 (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/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 (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/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.

U2 - 10.12688/wellcomeopenres.12583.3

DO - 10.12688/wellcomeopenres.12583.3

M3 - Journal article

C2 - 30175238

VL - 3

SP - 1

EP - 28

JO - Wellcome Open Research

JF - Wellcome Open Research

SN - 2398-502X

ER -