Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Maria Soler Artigas; Daan W. Loth; Louise V. Wain; Sina A. Gharib; Ma'en Obeidat; Wenbo Tang; Guangju Zhai; Jing Hua Zhao; Albert Vernon Smith; Jennifer E. Huffman; Eva Albrecht; Catherine M. Jackson; David M. Evans; Gemma Cadby; Myriam Fornage; Ani Manichaikul; Lorna M. Lopez; Toby Johnson; Melinda C. Aldrich; Thor Aspelund; Ines Barroso; Harry Campbell; Patricia A. Cassano; David J. Couper; Gudny Eiriksdottir; Nora Franceschini; Melissa Garcia; Christian Gieger; Gauti Kjartan Gislason; Ivica Grkovic; Christopher J. Hammond; Dana B. Hancock; Tamara B. Harris; Adaikalavan Ramasamy; Susan R. Heckbert; Markku Heliovaara; Georg Homuth; Pirro G. Hysi; Alan L. James; Stipan Jankovic; Bonnie R. Joubert; Stefan Karrasch; Norman Klopp; Beate Koch; Stephen B. Kritchevsky; Lenore J. Launer; Yongmei Liu; Laura R. Loehr; Andrew D. Morris; George Davey Smith; GIANT Consortium, Int Lung Canc Consortium

doi:10.1038/ng.941

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Maria Soler Artigas, Daan W. Loth, Louise V. Wain, Sina A. Gharib, Ma'en Obeidat, Wenbo Tang, Guangju Zhai, Jing Hua Zhao, Albert Vernon Smith, Jennifer E. Huffman, Eva Albrecht, Catherine M. Jackson, David M. Evans, Gemma Cadby, Myriam Fornage, Ani Manichaikul, Lorna M. Lopez, Toby Johnson, Melinda C. Aldrich, Thor AspelundInes Barroso, Harry Campbell, Patricia A. Cassano, David J. Couper, Gudny Eiriksdottir, Nora Franceschini, Melissa Garcia, Christian Gieger, Gauti Kjartan Gislason, Ivica Grkovic, Christopher J. Hammond, Dana B. Hancock, Tamara B. Harris, Adaikalavan Ramasamy, Susan R. Heckbert, Markku Heliovaara, Georg Homuth, Pirro G. Hysi, Alan L. James, Stipan Jankovic, Bonnie R. Joubert, Stefan Karrasch, Norman Klopp, Beate Koch, Stephen B. Kritchevsky, Lenore J. Launer, Yongmei Liu, Laura R. Loehr, Andrew D. Morris, George Davey Smith, GIANT Consortium, Int Lung Canc Consortium

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Abstract

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Original language	English
Pages (from-to)	1082-U70
Number of pages	11
Journal	Nature Genetics
Volume	43
Issue number	11
DOIs	https://doi.org/10.1038/ng.941
Publication status	Published - Nov 2011

Keywords

OBSTRUCTIVE PULMONARY-DISEASE
GENETIC-VARIATION
BLOOD-PRESSURE
VARIANTS
METAANALYSIS
RISK
PROTEIN
POLYMORPHISMS
POPULATION
EXPRESSION

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Artigas, M. S., Loth, D. W., Wain, L. V., Gharib, S. A., Obeidat, M., Tang, W., Zhai, G., Zhao, J. H., Smith, A. V., Huffman, J. E., Albrecht, E., Jackson, C. M., Evans, D. M., Cadby, G., Fornage, M., Manichaikul, A., Lopez, L. M., Johnson, T., Aldrich, M. C., ... GIANT Consortium, Int Lung Canc Consortium (2011). Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nature Genetics, 43(11), 1082-U70. https://doi.org/10.1038/ng.941

@article{065c77acedd74c279771ea5af1790152,

title = "Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function",

abstract = "Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.",

keywords = "OBSTRUCTIVE PULMONARY-DISEASE, GENETIC-VARIATION, BLOOD-PRESSURE, VARIANTS, METAANALYSIS, RISK, PROTEIN, POLYMORPHISMS, POPULATION, EXPRESSION",

author = "Artigas, {Maria Soler} and Loth, {Daan W.} and Wain, {Louise V.} and Gharib, {Sina A.} and Ma'en Obeidat and Wenbo Tang and Guangju Zhai and Zhao, {Jing Hua} and Smith, {Albert Vernon} and Huffman, {Jennifer E.} and Eva Albrecht and Jackson, {Catherine M.} and Evans, {David M.} and Gemma Cadby and Myriam Fornage and Ani Manichaikul and Lopez, {Lorna M.} and Toby Johnson and Aldrich, {Melinda C.} and Thor Aspelund and Ines Barroso and Harry Campbell and Cassano, {Patricia A.} and Couper, {David J.} and Gudny Eiriksdottir and Nora Franceschini and Melissa Garcia and Christian Gieger and Gislason, {Gauti Kjartan} and Ivica Grkovic and Hammond, {Christopher J.} and Hancock, {Dana B.} and Harris, {Tamara B.} and Adaikalavan Ramasamy and Heckbert, {Susan R.} and Markku Heliovaara and Georg Homuth and Hysi, {Pirro G.} and James, {Alan L.} and Stipan Jankovic and Joubert, {Bonnie R.} and Stefan Karrasch and Norman Klopp and Beate Koch and Kritchevsky, {Stephen B.} and Launer, {Lenore J.} and Yongmei Liu and Loehr, {Laura R.} and Morris, {Andrew D.} and Smith, {George Davey} and {GIANT Consortium, Int Lung Canc Consortium}",

year = "2011",

month = nov,

doi = "10.1038/ng.941",

language = "English",

volume = "43",

pages = "1082--U70",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

}

Artigas, MS, Loth, DW, Wain, LV, Gharib, SA, Obeidat, M, Tang, W, Zhai, G, Zhao, JH, Smith, AV, Huffman, JE, Albrecht, E, Jackson, CM, Evans, DM, Cadby, G, Fornage, M, Manichaikul, A, Lopez, LM, Johnson, T, Aldrich, MC, Aspelund, T, Barroso, I, Campbell, H, Cassano, PA, Couper, DJ, Eiriksdottir, G, Franceschini, N, Garcia, M, Gieger, C, Gislason, GK, Grkovic, I, Hammond, CJ, Hancock, DB, Harris, TB, Ramasamy, A, Heckbert, SR, Heliovaara, M, Homuth, G, Hysi, PG, James, AL, Jankovic, S, Joubert, BR, Karrasch, S, Klopp, N, Koch, B, Kritchevsky, SB, Launer, LJ, Liu, Y, Loehr, LR, Morris, AD, Smith, GD & GIANT Consortium, Int Lung Canc Consortium 2011, 'Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function', Nature Genetics, vol. 43, no. 11, pp. 1082-U70. https://doi.org/10.1038/ng.941

TY - JOUR

T1 - Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

AU - Artigas, Maria Soler

AU - Loth, Daan W.

AU - Wain, Louise V.

AU - Gharib, Sina A.

AU - Obeidat, Ma'en

AU - Tang, Wenbo

AU - Zhai, Guangju

AU - Zhao, Jing Hua

AU - Smith, Albert Vernon

AU - Huffman, Jennifer E.

AU - Albrecht, Eva

AU - Jackson, Catherine M.

AU - Evans, David M.

AU - Cadby, Gemma

AU - Fornage, Myriam

AU - Manichaikul, Ani

AU - Lopez, Lorna M.

AU - Johnson, Toby

AU - Aldrich, Melinda C.

AU - Aspelund, Thor

AU - Barroso, Ines

AU - Campbell, Harry

AU - Cassano, Patricia A.

AU - Couper, David J.

AU - Eiriksdottir, Gudny

AU - Franceschini, Nora

AU - Garcia, Melissa

AU - Gieger, Christian

AU - Gislason, Gauti Kjartan

AU - Grkovic, Ivica

AU - Hammond, Christopher J.

AU - Hancock, Dana B.

AU - Harris, Tamara B.

AU - Ramasamy, Adaikalavan

AU - Heckbert, Susan R.

AU - Heliovaara, Markku

AU - Homuth, Georg

AU - Hysi, Pirro G.

AU - James, Alan L.

AU - Jankovic, Stipan

AU - Joubert, Bonnie R.

AU - Karrasch, Stefan

AU - Klopp, Norman

AU - Koch, Beate

AU - Kritchevsky, Stephen B.

AU - Launer, Lenore J.

AU - Liu, Yongmei

AU - Loehr, Laura R.

AU - Morris, Andrew D.

AU - Smith, George Davey

AU - GIANT Consortium, Int Lung Canc Consortium

PY - 2011/11

Y1 - 2011/11

N2 - Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

AB - Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - GENETIC-VARIATION

KW - BLOOD-PRESSURE

KW - VARIANTS

KW - METAANALYSIS

KW - RISK

KW - PROTEIN

KW - POLYMORPHISMS

KW - POPULATION

KW - EXPRESSION

U2 - 10.1038/ng.941

DO - 10.1038/ng.941

M3 - Article

C2 - 21946350

SN - 1061-4036

VL - 43

SP - 1082-U70

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Abstract

Keywords

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