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

Victoria E Jackson; Jeanne C Latourelle; Louise V Wain; Albert V Smith; Megan L Grove; Traci M Bartz; Ma'en Obeidat; Michael A Province; Wei Gao; Beenish Qaiser; David J Porteous; Patricia A Cassano; Tarunveer S Ahluwalia; Niels Grarup; Jin Li; Elisabeth Altmaier; Jonathan Marten; Sarah E Harris; Ani Manichaikul; Tess D Pottinger; Ruifang Li-Gao; Allan Lind-Thomsen; Anubha Mahajan; Lies Lahousse; Medea Imboden; Alexander Teumer; Bram Prins; Leo-Pekka Lyytikäinen; Gudny Eiriksdottir; Nora Franceschini; Colleen M Sitlani; Jennifer A Brody; Yohan Bossé; Wim Timens; Aldi Kraja; Anu Loukola; Wenbo Tang; Yongmei Liu; Jette Bork-Jensen; Johanne M Justesen; Allan Linneberg; Leslie A Lange; Rajesh Rawal; Stefan Karrasch; Jennifer E Huffman; Blair H Smith; Lars Lind; Charlotta Pisinger; Torben Hansen; Henrik Vestergaard; Understanding Society Scientific Group

doi:10.12688/wellcomeopenres.12583.3

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

Victoria E Jackson, Jeanne C Latourelle, Louise V Wain, Albert V Smith, Megan L Grove, Traci M Bartz, Ma'en Obeidat, Michael A Province, Wei Gao, Beenish Qaiser, David J Porteous, Patricia A Cassano, Tarunveer S Ahluwalia, Niels Grarup, Jin Li, Elisabeth Altmaier, Jonathan Marten, Sarah E Harris, Ani Manichaikul, Tess D PottingerRuifang Li-Gao, Allan Lind-Thomsen, Anubha Mahajan, Lies Lahousse, Medea Imboden, Alexander Teumer, Bram Prins, Leo-Pekka Lyytikäinen, Gudny Eiriksdottir, Nora Franceschini, Colleen M Sitlani, Jennifer A Brody, Yohan Bossé, Wim Timens, Aldi Kraja, Anu Loukola, Wenbo Tang, Yongmei Liu, Jette Bork-Jensen, Johanne M Justesen, Allan Linneberg, Leslie A Lange, Rajesh Rawal, Stefan Karrasch, Jennifer E Huffman, Blair H Smith, Lars Lind, Charlotta Pisinger, Torben Hansen, Henrik Vestergaard, Understanding Society Scientific Group

10 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Wellcome Open Research
Vol/bind	3
Sider (fra-til)	1-28
ISSN	2398-502X
DOI	https://doi.org/10.12688/wellcomeopenres.12583.3
Status	Udgivet - 2018

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10.12688/wellcomeopenres.12583.3Licens: CC BY

pmc6081985?pdf=renderForlagets udgivne version, 1,14 MBLicens: CC BY

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Jackson, V. E., Latourelle, J. C., Wain, L. V., Smith, A. V., Grove, M. L., Bartz, T. M., Obeidat, M., Province, M. A., Gao, W., Qaiser, B., Porteous, D. J., Cassano, P. A., Ahluwalia, T. S., Grarup, N., Li, J., Altmaier, E., Marten, J., Harris, S. E., Manichaikul, A., ... Understanding Society Scientific Group (2018). Meta-analysis of exome array data identifies six novel genetic loci for lung function. Wellcome Open Research, 3, 1-28. https://doi.org/10.12688/wellcomeopenres.12583.3

Jackson, VE, Latourelle, JC, Wain, LV, Smith, AV, Grove, ML, Bartz, TM, Obeidat, M, Province, MA, Gao, W, Qaiser, B, Porteous, DJ, Cassano, PA, Ahluwalia, TS , Grarup, N, Li, J, Altmaier, E, Marten, J, Harris, SE, Manichaikul, A, Pottinger, TD, Li-Gao, R, Lind-Thomsen, A, Mahajan, A, Lahousse, L, Imboden, M, Teumer, A, Prins, B, Lyytikäinen, L-P, Eiriksdottir, G, Franceschini, N, Sitlani, CM, Brody, JA, Bossé, Y, Timens, W, Kraja, A, Loukola, A, Tang, W, Liu, Y, Bork-Jensen, J, Justesen, JM , Linneberg, A, Lange, LA, Rawal, R, Karrasch, S, Huffman, JE, Smith, BH, Lind, L, Pisinger, C, Hansen, T , Vestergaard, H & Understanding Society Scientific Group 2018, 'Meta-analysis of exome array data identifies six novel genetic loci for lung function', Wellcome Open Research, bind 3, s. 1-28. https://doi.org/10.12688/wellcomeopenres.12583.3

@article{8387619940e64a73b1a9b04acef7fc3b,

title = "Meta-analysis of exome array data identifies six novel genetic loci for lung function",

abstract = "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.",

author = "Jackson, {Victoria E} and Latourelle, {Jeanne C} and Wain, {Louise V} and Smith, {Albert V} and Grove, {Megan L} and Bartz, {Traci M} and Ma'en Obeidat and Province, {Michael A} and Wei Gao and Beenish Qaiser and Porteous, {David J} and Cassano, {Patricia A} and Ahluwalia, {Tarunveer S} and Niels Grarup and Jin Li and Elisabeth Altmaier and Jonathan Marten and Harris, {Sarah E} and Ani Manichaikul and Pottinger, {Tess D} and Ruifang Li-Gao and Allan Lind-Thomsen and Anubha Mahajan and Lies Lahousse and Medea Imboden and Alexander Teumer and Bram Prins and Leo-Pekka Lyytik{\"a}inen and Gudny Eiriksdottir and Nora Franceschini and Sitlani, {Colleen M} and Brody, {Jennifer A} and Yohan Boss{\'e} and Wim Timens and Aldi Kraja and Anu Loukola and Wenbo Tang and Yongmei Liu and Jette Bork-Jensen and Justesen, {Johanne M} and Allan Linneberg and Lange, {Leslie A} and Rajesh Rawal and Stefan Karrasch and Huffman, {Jennifer E} and Smith, {Blair H} and Lars Lind and Charlotta Pisinger and Torben Hansen and Henrik Vestergaard and {Understanding Society Scientific Group}",

year = "2018",

doi = "10.12688/wellcomeopenres.12583.3",

language = "English",

volume = "3",

pages = "1--28",

journal = "Wellcome Open Research",

issn = "2398-502X",

publisher = "F1000 Research Ltd.",

}

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 (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.

U2 - 10.12688/wellcomeopenres.12583.3

DO - 10.12688/wellcomeopenres.12583.3

M3 - Journal article

C2 - 30175238

SN - 2398-502X

VL - 3

SP - 1

EP - 28

JO - Wellcome Open Research

JF - Wellcome Open Research

ER -

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

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