Genome-wide association analysis identifies six new loci associated with forced vital capacity

Daan W. Loth; Maria Soler Artigas; Sina A. Gharib; Louise V. Wain; Nora Franceschini; Beate Koch; Tess D. Pottinger; Albert Vernon Smith; Qing Duan; Chris Oldmeadow; Mi Kyeong Lee; David P. Strachan; Alan L. James; Jennifer E. Huffman; Veronique Vitart; Adaikalavan Ramasamy; Nicholas J. Wareham; Jaakko Kaprio; Xin-Qun Wang; Holly Trochet; Mika Kähönen; Claudia Flexeder; Eva Albrecht; Lorna M. Lopez; Kim de Jong; Bharat Thyagarajan; Alexessander Couto Alves; Stefan Enroth; Ernst Omenaas; Peter K. Joshi; Tove Fall; Ana Viñuela; Lenore J. Launer; Laura R. Loehr; Myriam Fornage; Guo Li; Jemma B. Wilk; Wenbo Tang; Ani Manichaikul; Lies Lahousse; Tamara B. Harris; Kari E. North; Alicja R. Rudnicka; Jennie  Hui; Xiangjun Gu; Thomas Lumley; Alan F. Wright; Nicholas D. Hastie; Susan Campbell; Generation Scotland; Blair H. Smith; Martin D. Tobin; Stephanie J. London

doi:10.1038/ng.3011

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Daan W. Loth, Maria Soler Artigas, Sina A. Gharib, Louise V. Wain, Nora Franceschini, Beate Koch, Tess D. Pottinger, Albert Vernon Smith, Qing Duan, Chris Oldmeadow, Mi Kyeong Lee, David P. Strachan, Alan L. James, Jennifer E. Huffman, Veronique Vitart, Adaikalavan Ramasamy, Nicholas J. Wareham, Jaakko Kaprio, Xin-Qun Wang, Holly TrochetMika Kähönen, Claudia Flexeder, Eva Albrecht, Lorna M. Lopez, Kim de Jong, Bharat Thyagarajan, Alexessander Couto Alves, Stefan Enroth, Ernst Omenaas, Peter K. Joshi, Tove Fall, Ana Viñuela, Lenore J. Launer, Laura R. Loehr, Myriam Fornage, Guo Li, Jemma B. Wilk, Wenbo Tang, Ani Manichaikul, Lies Lahousse, Tamara B. Harris, Kari E. North, Alicja R. Rudnicka, Jennie Hui, Xiangjun Gu, Thomas Lumley, Alan F. Wright, Nicholas D. Hastie, Susan Campbell, Generation Scotland, Blair H. Smith, Martin D. Tobin (Lead / Corresponding author), Stephanie J. London (Lead / Corresponding author)

Population Health and Genomics

Research output: Contribution to journal › Article › peer-review

113 Citations (Scopus)

Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P <5 × 10) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

Original language	English
Pages (from-to)	669-677
Number of pages	9
Journal	Nature Genetics
Volume	46
Issue number	7
Early online date	15 Jun 2014
DOIs	https://doi.org/10.1038/ng.3011
Publication status	Published - Jul 2014

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.3011

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Loth, D. W., Artigas, M. S., Gharib, S. A., Wain, L. V., Franceschini, N., Koch, B., Pottinger, T. D., Smith, A. V., Duan, Q., Oldmeadow, C., Lee, M. K., Strachan, D. P., James, A. L., Huffman, J. E., Vitart, V., Ramasamy, A., Wareham, N. J., Kaprio, J., Wang, X.-Q., ... London, S. J. (2014). Genome-wide association analysis identifies six new loci associated with forced vital capacity. Nature Genetics, 46(7), 669-677. https://doi.org/10.1038/ng.3011

@article{d52913de608449c7b1b55c1e46ca9174,

title = "Genome-wide association analysis identifies six new loci associated with forced vital capacity",

abstract = "Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P <5 × 10) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.",

author = "Loth, {Daan W.} and Artigas, {Maria Soler} and Gharib, {Sina A.} and Wain, {Louise V.} and Nora Franceschini and Beate Koch and Pottinger, {Tess D.} and Smith, {Albert Vernon} and Qing Duan and Chris Oldmeadow and Lee, {Mi Kyeong} and Strachan, {David P.} and James, {Alan L.} and Huffman, {Jennifer E.} and Veronique Vitart and Adaikalavan Ramasamy and Wareham, {Nicholas J.} and Jaakko Kaprio and Xin-Qun Wang and Holly Trochet and Mika K{\"a}h{\"o}nen and Claudia Flexeder and Eva Albrecht and Lopez, {Lorna M.} and {de Jong}, Kim and Bharat Thyagarajan and Alves, {Alexessander Couto} and Stefan Enroth and Ernst Omenaas and Joshi, {Peter K.} and Tove Fall and Ana Vi{\~n}uela and Launer, {Lenore J.} and Loehr, {Laura R.} and Myriam Fornage and Guo Li and Wilk, {Jemma B.} and Wenbo Tang and Ani Manichaikul and Lies Lahousse and Harris, {Tamara B.} and North, {Kari E.} and Rudnicka, {Alicja R.} and Jennie Hui and Xiangjun Gu and Thomas Lumley and Wright, {Alan F.} and Hastie, {Nicholas D.} and Susan Campbell and {Generation Scotland} and Smith, {Blair H.} and Tobin, {Martin D.} and London, {Stephanie J.}",

year = "2014",

month = jul,

doi = "10.1038/ng.3011",

language = "English",

volume = "46",

pages = "669--677",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "7",

}

Loth, DW, Artigas, MS, Gharib, SA, Wain, LV, Franceschini, N, Koch, B, Pottinger, TD, Smith, AV, Duan, Q, Oldmeadow, C, Lee, MK, Strachan, DP, James, AL, Huffman, JE, Vitart, V, Ramasamy, A, Wareham, NJ, Kaprio, J, Wang, X-Q, Trochet, H, Kähönen, M, Flexeder, C, Albrecht, E, Lopez, LM, de Jong, K, Thyagarajan, B, Alves, AC, Enroth, S, Omenaas, E, Joshi, PK, Fall, T, Viñuela, A, Launer, LJ, Loehr, LR, Fornage, M, Li, G, Wilk, JB, Tang, W, Manichaikul, A, Lahousse, L, Harris, TB, North, KE, Rudnicka, AR, Hui, J, Gu, X, Lumley, T, Wright, AF, Hastie, ND, Campbell, S, Generation Scotland, Smith, BH, Tobin, MD & London, SJ 2014, 'Genome-wide association analysis identifies six new loci associated with forced vital capacity', Nature Genetics, vol. 46, no. 7, pp. 669-677. https://doi.org/10.1038/ng.3011

TY - JOUR

T1 - Genome-wide association analysis identifies six new loci associated with forced vital capacity

AU - Loth, Daan W.

AU - Artigas, Maria Soler

AU - Gharib, Sina A.

AU - Wain, Louise V.

AU - Franceschini, Nora

AU - Koch, Beate

AU - Pottinger, Tess D.

AU - Smith, Albert Vernon

AU - Duan, Qing

AU - Oldmeadow, Chris

AU - Lee, Mi Kyeong

AU - Strachan, David P.

AU - James, Alan L.

AU - Huffman, Jennifer E.

AU - Vitart, Veronique

AU - Ramasamy, Adaikalavan

AU - Wareham, Nicholas J.

AU - Kaprio, Jaakko

AU - Wang, Xin-Qun

AU - Trochet, Holly

AU - Kähönen, Mika

AU - Flexeder, Claudia

AU - Albrecht, Eva

AU - Lopez, Lorna M.

AU - de Jong, Kim

AU - Thyagarajan, Bharat

AU - Alves, Alexessander Couto

AU - Enroth, Stefan

AU - Omenaas, Ernst

AU - Joshi, Peter K.

AU - Fall, Tove

AU - Viñuela, Ana

AU - Launer, Lenore J.

AU - Loehr, Laura R.

AU - Fornage, Myriam

AU - Li, Guo

AU - Wilk, Jemma B.

AU - Tang, Wenbo

AU - Manichaikul, Ani

AU - Lahousse, Lies

AU - Harris, Tamara B.

AU - North, Kari E.

AU - Rudnicka, Alicja R.

AU - Hui, Jennie

AU - Gu, Xiangjun

AU - Lumley, Thomas

AU - Wright, Alan F.

AU - Hastie, Nicholas D.

AU - Campbell, Susan

AU - Generation Scotland

AU - Smith, Blair H.

AU - Tobin, Martin D.

AU - London, Stephanie J.

PY - 2014/7

Y1 - 2014/7

N2 - Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P <5 × 10) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

AB - Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P <5 × 10) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

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U2 - 10.1038/ng.3011

DO - 10.1038/ng.3011

M3 - Article

C2 - 24929828

AN - SCOPUS:84903637201

SN - 1061-4036

VL - 46

SP - 669

EP - 677

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Abstract

ASJC Scopus subject areas

UN SDGs

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Smith, Blair, FRSE MD MEd FRCGP FHEA FFPMRCA FRCP Edin

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Genome-wide association analysis identifies six new loci associated with forced vital capacity

Abstract

ASJC Scopus subject areas

UN SDGs

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Smith, Blair, FRSE MD MEd FRCGP FHEA FFPMRCA FRCP Edin

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