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

D.W. Loth; M.S. Artigas; S.A. Gharib; L.V. Wain; N. Franceschini; B. Koch; T.D. Pottinger; A.V. Smith; Q. Duan; C.J. Oldmeadow; M. Lee; D.P. Strachan; Alan James; J.E. Huffman; V. Vitart; A. Ramasamy; N.J. Wareham; J. Kaprio; X. Wang; H. Trochet; M. Kähönen; C. Flexeder; E. Albrecht; L.M. Lopez; K. De Jong; B. Thyagarajan; A.C. Alves; S. Enroth; E.R. Omenaas; P.K. Joshi; T. Fall; A. Viñuela; L.J. Launer; L.R. Loehr; M. Fornage; G. Li; J.B. Wilk; W. Tang; A. Manichaikul; L. Lahousse; T.B. Harris; K.E. North; A.R. Rudnicka; Jennie Hui; X. Gu; T.S. Lumley; A.F. Wright; N.D. Hastie; S. Campbell; R. Kumar; I. Pin; R.A. Scott; K.H. Pietiláinen; I. Surakka; Y. Liu; E.G. Holliday; H. Schulz; J. Heinrich; G.C. Davies; J.M. Vonk; M.K. Wojczynski; A.M. Pouta; A.M. Johansson; S.H. Wild; E. Ingelsson; F.F. Rivadeneira; H. Völzke; P.G. Hysi; G. Eiríksdóttir; A.C. Morrison; J.I. Rotter; W. Gao; D.S. Postma; W.B. White; S.S. Rich; A. Hofman; T. Aspelund; D.J. Couper; L.J. Smith; B.M. Psaty; K.K. Lohman; E.G. Burchard; A.G. Uitterlinden; M.E. Garcia; B.R. Joubert; W.L. Mcardle; A.W.B.M. Musk; N.N. Hansel; S.R. Heckbert; L. Zgaga; J.B.J. Van Meurs; P. Navarro; I. Rudan; Y. Oh; S. Redline; D.L. Jarvis; J. Zhao; T. Rantanen; G.T. O'Connor; S.O. Ripatti; R.J. Scott; S. Karrasch; H. Grallert; N.C. Gaddis; J.M. Starr; C. Wijmenga; R.L. Minster; D.J. Lederer; J.J. Pekkanen; U.B. Gyllensten; H.S. Campbell; A.P. Morris; S. Gläser; C.J. Hammond; K.M. Burkart; John Beilby; S.B. Kritchevsky; V.G. Gudnason; D.B. Hancock; O.D. Williams; O. Polašek; T. Zemunik; I. Kolčić; M.F. Petrini; M. Wjst; W. Kim; D.J. Porteous; G. Scotland; B.H. Smith; A. Viljanen; M.M. Heliövaara; J.R. Attia; I. Sayers; R. Hampel; C. Gieger; I.J. Deary; H.M. Boezen; A.B. Newman; M.R. Järvelin; J.F.F. Wilson; L. Lind; B.C.C.H. Stricker; A. Teumer; T.D. Spector; E. Melén; M.J. Peters; L.A. Lange; R.G. Barr; K.R. Bracke; F.M. Verhamme; J. Sung; P.S. Hiemstra; P.A. Cassano; A. Sood; C. Hayward; J.P. Dupuis; I.P. Hall; G.G. Brusselle; M.D. Tobin; S.J. London

doi:10.1038/ng.3011

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

D.W. Loth, M.S. Artigas, S.A. Gharib, L.V. Wain, N. Franceschini, B. Koch, T.D. Pottinger, A.V. Smith, Q. Duan, C.J. Oldmeadow, M. Lee, D.P. Strachan, Alan James, J.E. Huffman, V. Vitart, A. Ramasamy, N.J. Wareham, J. Kaprio, X. Wang, H. TrochetM. Kähönen, C. Flexeder, E. Albrecht, L.M. Lopez, K. De Jong, B. Thyagarajan, A.C. Alves, S. Enroth, E.R. Omenaas, P.K. Joshi, T. Fall, A. Viñuela, L.J. Launer, L.R. Loehr, M. Fornage, G. Li, J.B. Wilk, W. Tang, A. Manichaikul, L. Lahousse, T.B. Harris, K.E. North, A.R. Rudnicka, Jennie Hui, X. Gu, T.S. Lumley, A.F. Wright, N.D. Hastie, S. Campbell, R. Kumar, I. Pin, R.A. Scott, K.H. Pietiláinen, I. Surakka, Y. Liu, E.G. Holliday, H. Schulz, J. Heinrich, G.C. Davies, J.M. Vonk, M.K. Wojczynski, A.M. Pouta, A.M. Johansson, S.H. Wild, E. Ingelsson, F.F. Rivadeneira, H. Völzke, P.G. Hysi, G. Eiríksdóttir, A.C. Morrison, J.I. Rotter, W. Gao, D.S. Postma, W.B. White, S.S. Rich, A. Hofman, T. Aspelund, D.J. Couper, L.J. Smith, B.M. Psaty, K.K. Lohman, E.G. Burchard, A.G. Uitterlinden, M.E. Garcia, B.R. Joubert, W.L. Mcardle, A.W.B.M. Musk, N.N. Hansel, S.R. Heckbert, L. Zgaga, J.B.J. Van Meurs, P. Navarro, I. Rudan, Y. Oh, S. Redline, D.L. Jarvis, J. Zhao, T. Rantanen, G.T. O'Connor, S.O. Ripatti, R.J. Scott, S. Karrasch, H. Grallert, N.C. Gaddis, J.M. Starr, C. Wijmenga, R.L. Minster, D.J. Lederer, J.J. Pekkanen, U.B. Gyllensten, H.S. Campbell, A.P. Morris, S. Gläser, C.J. Hammond, K.M. Burkart, John Beilby, S.B. Kritchevsky, V.G. Gudnason, D.B. Hancock, O.D. Williams, O. Polašek, T. Zemunik, I. Kolčić, M.F. Petrini, M. Wjst, W. Kim, D.J. Porteous, G. Scotland, B.H. Smith, A. Viljanen, M.M. Heliövaara, J.R. Attia, I. Sayers, R. Hampel, C. Gieger, I.J. Deary, H.M. Boezen, A.B. Newman, M.R. Järvelin, J.F.F. Wilson, L. Lind, B.C.C.H. Stricker, A. Teumer, T.D. Spector, E. Melén, M.J. Peters, L.A. Lange, R.G. Barr, K.R. Bracke, F.M. Verhamme, J. Sung, P.S. Hiemstra, P.A. Cassano, A. Sood, C. Hayward, J.P. Dupuis, I.P. Hall, G.G. Brusselle, M.D. Tobin, S.J. London

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

114 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 × 10-8) 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.© 2014 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	669-677
Journal	Nature Genetics
Volume	46
Issue number	7
DOIs	https://doi.org/10.1038/ng.3011
Publication status	Published - 2014

UN SDGs

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

Access to Document

10.1038/ng.3011

Cite this

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. J., Lee, M., Strachan, D. P., James, A., Huffman, J. E., Vitart, V., Ramasamy, A., Wareham, N. J., Kaprio, J., Wang, X., ... 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{dcd6d38d772c42f2bcf4aaf3c19568e7,

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 × 10-8) 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.{\textcopyright} 2014 Nature America, Inc. All rights reserved.",

author = "D.W. Loth and M.S. Artigas and S.A. Gharib and L.V. Wain and N. Franceschini and B. Koch and T.D. Pottinger and A.V. Smith and Q. Duan and C.J. Oldmeadow and M. Lee and D.P. Strachan and Alan James and J.E. Huffman and V. Vitart and A. Ramasamy and N.J. Wareham and J. Kaprio and X. Wang and H. Trochet and M. K{\"a}h{\"o}nen and C. Flexeder and E. Albrecht and L.M. Lopez and {De Jong}, K. and B. Thyagarajan and A.C. Alves and S. Enroth and E.R. Omenaas and P.K. Joshi and T. Fall and A. Vi{\~n}uela and L.J. Launer and L.R. Loehr and M. Fornage and G. Li and J.B. Wilk and W. Tang and A. Manichaikul and L. Lahousse and T.B. Harris and K.E. North and A.R. Rudnicka and Jennie Hui and X. Gu and T.S. Lumley and A.F. Wright and N.D. Hastie and S. Campbell and R. Kumar and I. Pin and R.A. Scott and K.H. Pietil{\'a}inen and I. Surakka and Y. Liu and E.G. Holliday and H. Schulz and J. Heinrich and G.C. Davies and J.M. Vonk and M.K. Wojczynski and A.M. Pouta and A.M. Johansson and S.H. Wild and E. Ingelsson and F.F. Rivadeneira and H. V{\"o}lzke and P.G. Hysi and G. Eir{\'i}ksd{\'o}ttir and A.C. Morrison and J.I. Rotter and W. Gao and D.S. Postma and W.B. White and S.S. Rich and A. Hofman and T. Aspelund and D.J. Couper and L.J. Smith and B.M. Psaty and K.K. Lohman and E.G. Burchard and A.G. Uitterlinden and M.E. Garcia and B.R. Joubert and W.L. Mcardle and A.W.B.M. Musk and N.N. Hansel and S.R. Heckbert and L. Zgaga and {Van Meurs}, J.B.J. and P. Navarro and I. Rudan and Y. Oh and S. Redline and D.L. Jarvis and J. Zhao and T. Rantanen and G.T. O'Connor and S.O. Ripatti and R.J. Scott and S. Karrasch and H. Grallert and N.C. Gaddis and J.M. Starr and C. Wijmenga and R.L. Minster and D.J. Lederer and J.J. Pekkanen and U.B. Gyllensten and H.S. Campbell and A.P. Morris and S. Gl{\"a}ser and C.J. Hammond and K.M. Burkart and John Beilby and S.B. Kritchevsky and V.G. Gudnason and D.B. Hancock and O.D. Williams and O. Pola{\v s}ek and T. Zemunik and I. Kol{\v c}i{\'c} and M.F. Petrini and M. Wjst and W. Kim and D.J. Porteous and G. Scotland and B.H. Smith and A. Viljanen and M.M. Heli{\"o}vaara and J.R. Attia and I. Sayers and R. Hampel and C. Gieger and I.J. Deary and H.M. Boezen and A.B. Newman and M.R. J{\"a}rvelin and J.F.F. Wilson and L. Lind and B.C.C.H. Stricker and A. Teumer and T.D. Spector and E. Mel{\'e}n and M.J. Peters and L.A. Lange and R.G. Barr and K.R. Bracke and F.M. Verhamme and J. Sung and P.S. Hiemstra and P.A. Cassano and A. Sood and C. Hayward and J.P. Dupuis and I.P. Hall and G.G. Brusselle and M.D. Tobin and S.J. London",

year = "2014",

doi = "10.1038/ng.3011",

language = "English",

volume = "46",

pages = "669--677",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "7",

}

Loth, DW, Artigas, MS, Gharib, SA, Wain, LV, Franceschini, N, Koch, B, Pottinger, TD, Smith, AV, Duan, Q, Oldmeadow, CJ, Lee, M, Strachan, DP, James, A, Huffman, JE, Vitart, V, Ramasamy, A, Wareham, NJ, Kaprio, J, Wang, X, Trochet, H, Kähönen, M, Flexeder, C, Albrecht, E, Lopez, LM, De Jong, K, Thyagarajan, B, Alves, AC, Enroth, S, Omenaas, ER, 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, TS, Wright, AF, Hastie, ND, Campbell, S, Kumar, R, Pin, I, Scott, RA, Pietiláinen, KH, Surakka, I, Liu, Y, Holliday, EG, Schulz, H, Heinrich, J, Davies, GC, Vonk, JM, Wojczynski, MK, Pouta, AM, Johansson, AM, Wild, SH, Ingelsson, E, Rivadeneira, FF, Völzke, H, Hysi, PG, Eiríksdóttir, G, Morrison, AC, Rotter, JI, Gao, W, Postma, DS, White, WB, Rich, SS, Hofman, A, Aspelund, T, Couper, DJ, Smith, LJ, Psaty, BM, Lohman, KK, Burchard, EG, Uitterlinden, AG, Garcia, ME, Joubert, BR, Mcardle, WL, Musk, AWBM, Hansel, NN, Heckbert, SR, Zgaga, L, Van Meurs, JBJ, Navarro, P, Rudan, I, Oh, Y, Redline, S, Jarvis, DL, Zhao, J, Rantanen, T, O'Connor, GT, Ripatti, SO, Scott, RJ, Karrasch, S, Grallert, H, Gaddis, NC, Starr, JM, Wijmenga, C, Minster, RL, Lederer, DJ, Pekkanen, JJ, Gyllensten, UB, Campbell, HS, Morris, AP, Gläser, S, Hammond, CJ, Burkart, KM, Beilby, J, Kritchevsky, SB, Gudnason, VG, Hancock, DB, Williams, OD, Polašek, O, Zemunik, T, Kolčić, I, Petrini, MF, Wjst, M, Kim, W, Porteous, DJ, Scotland, G, Smith, BH, Viljanen, A, Heliövaara, MM, Attia, JR, Sayers, I, Hampel, R, Gieger, C, Deary, IJ, Boezen, HM, Newman, AB, Järvelin, MR, Wilson, JFF, Lind, L, Stricker, BCCH, Teumer, A, Spector, TD, Melén, E, Peters, MJ, Lange, LA, Barr, RG, Bracke, KR, Verhamme, FM, Sung, J, Hiemstra, PS, Cassano, PA, Sood, A, Hayward, C, Dupuis, JP, Hall, IP, Brusselle, GG, 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, D.W.

AU - Artigas, M.S.

AU - Gharib, S.A.

AU - Wain, L.V.

AU - Franceschini, N.

AU - Koch, B.

AU - Pottinger, T.D.

AU - Smith, A.V.

AU - Duan, Q.

AU - Oldmeadow, C.J.

AU - Lee, M.

AU - Strachan, D.P.

AU - James, Alan

AU - Huffman, J.E.

AU - Vitart, V.

AU - Ramasamy, A.

AU - Wareham, N.J.

AU - Kaprio, J.

AU - Wang, X.

AU - Trochet, H.

AU - Kähönen, M.

AU - Flexeder, C.

AU - Albrecht, E.

AU - Lopez, L.M.

AU - De Jong, K.

AU - Thyagarajan, B.

AU - Alves, A.C.

AU - Enroth, S.

AU - Omenaas, E.R.

AU - Joshi, P.K.

AU - Fall, T.

AU - Viñuela, A.

AU - Launer, L.J.

AU - Loehr, L.R.

AU - Fornage, M.

AU - Li, G.

AU - Wilk, J.B.

AU - Tang, W.

AU - Manichaikul, A.

AU - Lahousse, L.

AU - Harris, T.B.

AU - North, K.E.

AU - Rudnicka, A.R.

AU - Hui, Jennie

AU - Gu, X.

AU - Lumley, T.S.

AU - Wright, A.F.

AU - Hastie, N.D.

AU - Campbell, S.

AU - Kumar, R.

AU - Pin, I.

AU - Scott, R.A.

AU - Pietiláinen, K.H.

AU - Surakka, I.

AU - Liu, Y.

AU - Holliday, E.G.

AU - Schulz, H.

AU - Heinrich, J.

AU - Davies, G.C.

AU - Vonk, J.M.

AU - Wojczynski, M.K.

AU - Pouta, A.M.

AU - Johansson, A.M.

AU - Wild, S.H.

AU - Ingelsson, E.

AU - Rivadeneira, F.F.

AU - Völzke, H.

AU - Hysi, P.G.

AU - Eiríksdóttir, G.

AU - Morrison, A.C.

AU - Rotter, J.I.

AU - Gao, W.

AU - Postma, D.S.

AU - White, W.B.

AU - Rich, S.S.

AU - Hofman, A.

AU - Aspelund, T.

AU - Couper, D.J.

AU - Smith, L.J.

AU - Psaty, B.M.

AU - Lohman, K.K.

AU - Burchard, E.G.

AU - Uitterlinden, A.G.

AU - Garcia, M.E.

AU - Joubert, B.R.

AU - Mcardle, W.L.

AU - Musk, A.W.B.M.

AU - Hansel, N.N.

AU - Heckbert, S.R.

AU - Zgaga, L.

AU - Van Meurs, J.B.J.

AU - Navarro, P.

AU - Rudan, I.

AU - Oh, Y.

AU - Redline, S.

AU - Jarvis, D.L.

AU - Zhao, J.

AU - Rantanen, T.

AU - O'Connor, G.T.

AU - Ripatti, S.O.

AU - Scott, R.J.

AU - Karrasch, S.

AU - Grallert, H.

AU - Gaddis, N.C.

AU - Starr, J.M.

AU - Wijmenga, C.

AU - Minster, R.L.

AU - Lederer, D.J.

AU - Pekkanen, J.J.

AU - Gyllensten, U.B.

AU - Campbell, H.S.

AU - Morris, A.P.

AU - Gläser, S.

AU - Hammond, C.J.

AU - Burkart, K.M.

AU - Beilby, John

AU - Kritchevsky, S.B.

AU - Gudnason, V.G.

AU - Hancock, D.B.

AU - Williams, O.D.

AU - Polašek, O.

AU - Zemunik, T.

AU - Kolčić, I.

AU - Petrini, M.F.

AU - Wjst, M.

AU - Kim, W.

AU - Porteous, D.J.

AU - Scotland, G.

AU - Smith, B.H.

AU - Viljanen, A.

AU - Heliövaara, M.M.

AU - Attia, J.R.

AU - Sayers, I.

AU - Hampel, R.

AU - Gieger, C.

AU - Deary, I.J.

AU - Boezen, H.M.

AU - Newman, A.B.

AU - Järvelin, M.R.

AU - Wilson, J.F.F.

AU - Lind, L.

AU - Stricker, B.C.C.H.

AU - Teumer, A.

AU - Spector, T.D.

AU - Melén, E.

AU - Peters, M.J.

AU - Lange, L.A.

AU - Barr, R.G.

AU - Bracke, K.R.

AU - Verhamme, F.M.

AU - Sung, J.

AU - Hiemstra, P.S.

AU - Cassano, P.A.

AU - Sood, A.

AU - Hayward, C.

AU - Dupuis, J.P.

AU - Hall, I.P.

AU - Brusselle, G.G.

AU - Tobin, M.D.

AU - London, S.J.

PY - 2014

Y1 - 2014

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 × 10-8) 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.© 2014 Nature America, Inc. All rights reserved.

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 × 10-8) 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.© 2014 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.3011

DO - 10.1038/ng.3011

M3 - Article

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

UN SDGs

Access to Document

Fingerprint

Cite this