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

Daan W. Loth; María 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; Rajesh Kumar; Isabelle Pin; Robert A. Scott; Kirsi H. Pietiläinen; Ida Surakka; Yongmei Liu; Elizabeth G. Holliday; Holger Schulz; Joachim Heinrich; Gail Davies; Judith M. Vonk; Mary Wojczynski; Anneli Pouta; Asa Johansson; Sarah H. Wild; Erik Ingelsson; Fernando Rivadeneira; Henry Völzke; Pirro G. Hysi; Gudny Eiriksdottir; Alanna C. Morrison; Jerome I. Rotter; Wei Gao; Dirkje S. Postma; Wendy B. White; Stephen S. Rich; Albert Hofman; Thor Aspelund; David Couper; Lewis J. Smith; Bruce M. Psaty; Kurt Lohman; Esteban G. Burchard; André G. Uitterlinden; Melissa Garcia; Bonnie R. Joubert; Wendy L. McArdle; A. Bill Musk; Nadia Hansel; Susan R. Heckbert; Lina Zgaga; Joyce B.J. Van Meurs; Pau Navarro; Igor Rudan; Yeon Mok Oh; Susan Redline; Deborah L. Jarvis; Jing Hua Zhao; Taina Rantanen; George T. O'Connor; Samuli Ripatti; Rodney J. Scott; Stefan Karrasch; Harald Grallert; Nathan C. Gaddis; John M. Starr; Cisca Wijmenga; Ryan L. Minster; David J. Lederer; Juha Pekkanen; Ulf Gyllensten; Harry Campbell; Andrew P. Morris; Sven Gläser; Christopher J. Hammond; Kristin M. Burkart; John Beilby; Stephen B. Kritchevsky; Vilmundur Gudnason; Dana B. Hancock; O. Dale Williams; Ozren Polasek; Tatijana Zemunik; Ivana Kolcic; Marcy F. Petrini; Matthias Wjst; Woo Jin Kim; David J. Porteous; Generation Scotland; Blair H. Smith; Anne Viljanen; Markku Heliövaara; John R. Attia; Ian Sayers; Regina Hampel; Christian Gieger; Ian J. Deary; H. Marike Boezen; Anne Newman; Marjo Riitta Jarvelin; James F. Wilson; Lars Lind; Bruno H. Stricker; Alexander Teumer; Timothy D. Spector; Erik Melén; Marjolein J. Peters; Leslie A. Lange; R. Graham Barr; Ken R. Bracke; Fien M. Verhamme; Joohon Sung; Pieter S. Hiemstra; Patricia A. Cassano; Akshay Sood; Caroline Hayward; Josée Dupuis; Ian P. Hall; Guy G. Brusselle; 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, María 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, Rajesh Kumar, Isabelle Pin, Robert A. Scott, Kirsi H. Pietiläinen, Ida Surakka, Yongmei Liu, Elizabeth G. Holliday, Holger Schulz, Joachim Heinrich, Gail Davies, Judith M. Vonk, Mary Wojczynski, Anneli Pouta, Asa Johansson, Sarah H. Wild, Erik Ingelsson, Fernando Rivadeneira, Henry Völzke, Pirro G. Hysi, Gudny Eiriksdottir, Alanna C. Morrison, Jerome I. Rotter, Wei Gao, Dirkje S. Postma, Wendy B. White, Stephen S. Rich, Albert Hofman, Thor Aspelund, David Couper, Lewis J. Smith, Bruce M. Psaty, Kurt Lohman, Esteban G. Burchard, André G. Uitterlinden, Melissa Garcia, Bonnie R. Joubert, Wendy L. McArdle, A. Bill Musk, Nadia Hansel, Susan R. Heckbert, Lina Zgaga, Joyce B.J. Van Meurs, Pau Navarro, Igor Rudan, Yeon Mok Oh, Susan Redline, Deborah L. Jarvis, Jing Hua Zhao, Taina Rantanen, George T. O'Connor, Samuli Ripatti, Rodney J. Scott, Stefan Karrasch, Harald Grallert, Nathan C. Gaddis, John M. Starr, Cisca Wijmenga, Ryan L. Minster, David J. Lederer, Juha Pekkanen, Ulf Gyllensten, Harry Campbell, Andrew P. Morris, Sven Gläser, Christopher J. Hammond, Kristin M. Burkart, John Beilby, Stephen B. Kritchevsky, Vilmundur Gudnason, Dana B. Hancock, O. Dale Williams, Ozren Polasek, Tatijana Zemunik, Ivana Kolcic, Marcy F. Petrini, Matthias Wjst, Woo Jin Kim, David J. Porteous, Generation Scotland, Blair H. Smith, Anne Viljanen, Markku Heliövaara, John R. Attia, Ian Sayers, Regina Hampel, Christian Gieger, Ian J. Deary, H. Marike Boezen, Anne Newman, Marjo Riitta Jarvelin, James F. Wilson, Lars Lind, Bruno H. Stricker, Alexander Teumer, Timothy D. Spector, Erik Melén, Marjolein J. Peters, Leslie A. Lange, R. Graham Barr, Ken R. Bracke, Fien M. Verhamme, Joohon Sung, Pieter S. Hiemstra, Patricia A. Cassano, Akshay Sood, Caroline Hayward, Josée Dupuis, Ian P. Hall, Guy G. Brusselle, Martin D. Tobin, Stephanie J. London^*

^*Corresponding author for this work

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

98 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.

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

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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., 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

Loth, Daan W. ; Artigas, María Soler ; Gharib, Sina A. ; Wain, Louise V. ; Franceschini, Nora ; Koch, Beate ; Pottinger, Tess D. ; Smith, Albert Vernon ; Duan, Qing ; Oldmeadow, Chris ; Lee, Mi Kyeong ; Strachan, David P. ; James, Alan L. ; Huffman, Jennifer E. ; Vitart, Veronique ; Ramasamy, Adaikalavan ; Wareham, Nicholas J. ; Kaprio, Jaakko ; Wang, Xin Qun ; Trochet, Holly ; Kähönen, Mika ; Flexeder, Claudia ; Albrecht, Eva ; Lopez, Lorna M. ; De Jong, Kim ; Thyagarajan, Bharat ; Alves, Alexessander Couto ; Enroth, Stefan ; Omenaas, Ernst ; Joshi, Peter K. ; Fall, Tove ; Viñuela, Ana ; Launer, Lenore J. ; Loehr, Laura R. ; Fornage, Myriam ; Li, Guo ; Wilk, Jemma B. ; Tang, Wenbo ; Manichaikul, Ani ; Lahousse, Lies ; Harris, Tamara B. ; North, Kari E. ; Rudnicka, Alicja R. ; Hui, Jennie ; Gu, Xiangjun ; Lumley, Thomas ; Wright, Alan F. ; Hastie, Nicholas D. ; Campbell, Susan ; Kumar, Rajesh ; Pin, Isabelle ; Scott, Robert A. ; Pietiläinen, Kirsi H. ; Surakka, Ida ; Liu, Yongmei ; Holliday, Elizabeth G. ; Schulz, Holger ; Heinrich, Joachim ; Davies, Gail ; Vonk, Judith M. ; Wojczynski, Mary ; Pouta, Anneli ; Johansson, Asa ; Wild, Sarah H. ; Ingelsson, Erik ; Rivadeneira, Fernando ; Völzke, Henry ; Hysi, Pirro G. ; Eiriksdottir, Gudny ; Morrison, Alanna C. ; Rotter, Jerome I. ; Gao, Wei ; Postma, Dirkje S. ; White, Wendy B. ; Rich, Stephen S. ; Hofman, Albert ; Aspelund, Thor ; Couper, David ; Smith, Lewis J. ; Psaty, Bruce M. ; Lohman, Kurt ; Burchard, Esteban G. ; Uitterlinden, André G. ; Garcia, Melissa ; Joubert, Bonnie R. ; McArdle, Wendy L. ; Musk, A. Bill ; Hansel, Nadia ; Heckbert, Susan R. ; Zgaga, Lina ; Van Meurs, Joyce B.J. ; Navarro, Pau ; Rudan, Igor ; Oh, Yeon Mok ; Redline, Susan ; Jarvis, Deborah L. ; Zhao, Jing Hua ; Rantanen, Taina ; O'Connor, George T. ; Ripatti, Samuli ; Scott, Rodney J. ; Karrasch, Stefan ; Grallert, Harald ; Gaddis, Nathan C. ; Starr, John M. ; Wijmenga, Cisca ; Minster, Ryan L. ; Lederer, David J. ; Pekkanen, Juha ; Gyllensten, Ulf ; Campbell, Harry ; Morris, Andrew P. ; Gläser, Sven ; Hammond, Christopher J. ; Burkart, Kristin M. ; Beilby, John ; Kritchevsky, Stephen B. ; Gudnason, Vilmundur ; Hancock, Dana B. ; Williams, O. Dale ; Polasek, Ozren ; Zemunik, Tatijana ; Kolcic, Ivana ; Petrini, Marcy F. ; Wjst, Matthias ; Kim, Woo Jin ; Porteous, David J. ; Scotland, Generation ; Smith, Blair H. ; Viljanen, Anne ; Heliövaara, Markku ; Attia, John R. ; Sayers, Ian ; Hampel, Regina ; Gieger, Christian ; Deary, Ian J. ; Boezen, H. Marike ; Newman, Anne ; Jarvelin, Marjo Riitta ; Wilson, James F. ; Lind, Lars ; Stricker, Bruno H. ; Teumer, Alexander ; Spector, Timothy D. ; Melén, Erik ; Peters, Marjolein J. ; Lange, Leslie A. ; Barr, R. Graham ; Bracke, Ken R. ; Verhamme, Fien M. ; Sung, Joohon ; Hiemstra, Pieter S. ; Cassano, Patricia A. ; Sood, Akshay ; Hayward, Caroline ; Dupuis, Josée ; Hall, Ian P. ; Brusselle, Guy G. ; Tobin, Martin D. ; London, Stephanie J. / Genome-wide association analysis identifies six new loci associated with forced vital capacity. In: Nature Genetics. 2014 ; Vol. 46, No. 7. pp. 669-677.

@article{c76b5c7553884fb6ac2f709a906dbc1b,

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.",

author = "Loth, {Daan W.} and Artigas, {Mar{\'i}a 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 Wang, {Xin Qun} 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 Rajesh Kumar and Isabelle Pin and Scott, {Robert A.} and Pietil{\"a}inen, {Kirsi H.} and Ida Surakka and Yongmei Liu and Holliday, {Elizabeth G.} and Holger Schulz and Joachim Heinrich and Gail Davies and Vonk, {Judith M.} and Mary Wojczynski and Anneli Pouta and Asa Johansson and Wild, {Sarah H.} and Erik Ingelsson and Fernando Rivadeneira and Henry V{\"o}lzke and Hysi, {Pirro G.} and Gudny Eiriksdottir and Morrison, {Alanna C.} and Rotter, {Jerome I.} and Wei Gao and Postma, {Dirkje S.} and White, {Wendy B.} and Rich, {Stephen S.} and Albert Hofman and Thor Aspelund and David Couper and Smith, {Lewis J.} and Psaty, {Bruce M.} and Kurt Lohman and Burchard, {Esteban G.} and Uitterlinden, {Andr{\'e} G.} and Melissa Garcia and Joubert, {Bonnie R.} and McArdle, {Wendy L.} and Musk, {A. Bill} and Nadia Hansel and Heckbert, {Susan R.} and Lina Zgaga and {Van Meurs}, {Joyce B.J.} and Pau Navarro and Igor Rudan and Oh, {Yeon Mok} and Susan Redline and Jarvis, {Deborah L.} and Zhao, {Jing Hua} and Taina Rantanen and O'Connor, {George T.} and Samuli Ripatti and Scott, {Rodney J.} and Stefan Karrasch and Harald Grallert and Gaddis, {Nathan C.} and Starr, {John M.} and Cisca Wijmenga and Minster, {Ryan L.} and Lederer, {David J.} and Juha Pekkanen and Ulf Gyllensten and Harry Campbell and Morris, {Andrew P.} and Sven Gl{\"a}ser and Hammond, {Christopher J.} and Burkart, {Kristin M.} and John Beilby and Kritchevsky, {Stephen B.} and Vilmundur Gudnason and Hancock, {Dana B.} and Williams, {O. Dale} and Ozren Polasek and Tatijana Zemunik and Ivana Kolcic and Petrini, {Marcy F.} and Matthias Wjst and Kim, {Woo Jin} and Porteous, {David J.} and Generation Scotland and Smith, {Blair H.} and Anne Viljanen and Markku Heli{\"o}vaara and Attia, {John R.} and Ian Sayers and Regina Hampel and Christian Gieger and Deary, {Ian J.} and Boezen, {H. Marike} and Anne Newman and Jarvelin, {Marjo Riitta} and Wilson, {James F.} and Lars Lind and Stricker, {Bruno H.} and Alexander Teumer and Spector, {Timothy D.} and Erik Mel{\'e}n and Peters, {Marjolein J.} and Lange, {Leslie A.} and Barr, {R. Graham} and Bracke, {Ken R.} and Verhamme, {Fien M.} and Joohon Sung and Hiemstra, {Pieter S.} and Cassano, {Patricia A.} and Akshay Sood and Caroline Hayward and Jos{\'e}e Dupuis and Hall, {Ian P.} and Brusselle, {Guy G.} 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, XQ, 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, Kumar, R, Pin, I, Scott, RA, Pietiläinen, KH, Surakka, I, Liu, Y, Holliday, EG, Schulz, H, Heinrich, J, Davies, G, Vonk, JM, Wojczynski, M, Pouta, A, Johansson, A, Wild, SH, Ingelsson, E, Rivadeneira, F, Völzke, H, Hysi, PG, Eiriksdottir, G, Morrison, AC, Rotter, JI, Gao, W, Postma, DS, White, WB, Rich, SS, Hofman, A, Aspelund, T, Couper, D, Smith, LJ, Psaty, BM, Lohman, K, Burchard, EG, Uitterlinden, AG, Garcia, M, Joubert, BR, McArdle, WL, Musk, AB, Hansel, N, Heckbert, SR, Zgaga, L, Van Meurs, JBJ, Navarro, P, Rudan, I, Oh, YM, Redline, S, Jarvis, DL, Zhao, JH, Rantanen, T, O'Connor, GT, Ripatti, S, Scott, RJ, Karrasch, S, Grallert, H, Gaddis, NC, Starr, JM, Wijmenga, C, Minster, RL, Lederer, DJ, Pekkanen, J, Gyllensten, U, Campbell, H, Morris, AP, Gläser, S, Hammond, CJ, Burkart, KM, Beilby, J, Kritchevsky, SB, Gudnason, V, Hancock, DB, Williams, OD, Polasek, O, Zemunik, T, Kolcic, I, Petrini, MF, Wjst, M, Kim, WJ, Porteous, DJ, Scotland, G, Smith, BH, Viljanen, A, Heliövaara, M, Attia, JR, Sayers, I, Hampel, R, Gieger, C, Deary, IJ, Boezen, HM, Newman, A, Jarvelin, MR, Wilson, JF, Lind, L, Stricker, BH, 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, J, 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

Genome-wide association analysis identifies six new loci associated with forced vital capacity. / Loth, Daan W.; Artigas, María Soler; Gharib, Sina A.; Wain, Louise V.; Franceschini, Nora; Koch, Beate; Pottinger, Tess D.; Smith, Albert Vernon; Duan, Qing; Oldmeadow, Chris; Lee, Mi Kyeong; Strachan, David P.; James, Alan L.; Huffman, Jennifer E.; Vitart, Veronique; Ramasamy, Adaikalavan; Wareham, Nicholas J.; Kaprio, Jaakko; Wang, Xin Qun; Trochet, Holly; Kähönen, Mika; Flexeder, Claudia; Albrecht, Eva; Lopez, Lorna M.; De Jong, Kim; Thyagarajan, Bharat; Alves, Alexessander Couto; Enroth, Stefan; Omenaas, Ernst; Joshi, Peter K.; Fall, Tove; Viñuela, Ana; Launer, Lenore J.; Loehr, Laura R.; Fornage, Myriam; Li, Guo; Wilk, Jemma B.; Tang, Wenbo; Manichaikul, Ani; Lahousse, Lies; Harris, Tamara B.; North, Kari E.; Rudnicka, Alicja R.; Hui, Jennie; Gu, Xiangjun; Lumley, Thomas; Wright, Alan F.; Hastie, Nicholas D.; Campbell, Susan; Kumar, Rajesh; Pin, Isabelle; Scott, Robert A.; Pietiläinen, Kirsi H.; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G.; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M.; Wojczynski, Mary; Pouta, Anneli; Johansson, Asa; Wild, Sarah H.; Ingelsson, Erik; Rivadeneira, Fernando; Völzke, Henry; Hysi, Pirro G.; Eiriksdottir, Gudny; Morrison, Alanna C.; Rotter, Jerome I.; Gao, Wei; Postma, Dirkje S.; White, Wendy B.; Rich, Stephen S.; Hofman, Albert; Aspelund, Thor; Couper, David; Smith, Lewis J.; Psaty, Bruce M.; Lohman, Kurt; Burchard, Esteban G.; Uitterlinden, André G.; Garcia, Melissa; Joubert, Bonnie R.; McArdle, Wendy L.; Musk, A. Bill; Hansel, Nadia; Heckbert, Susan R.; Zgaga, Lina; Van Meurs, Joyce B.J.; Navarro, Pau; Rudan, Igor; Oh, Yeon Mok; Redline, Susan; Jarvis, Deborah L.; Zhao, Jing Hua; Rantanen, Taina; O'Connor, George T.; Ripatti, Samuli; Scott, Rodney J.; Karrasch, Stefan; Grallert, Harald; Gaddis, Nathan C.; Starr, John M.; Wijmenga, Cisca; Minster, Ryan L.; Lederer, David J.; Pekkanen, Juha; Gyllensten, Ulf; Campbell, Harry; Morris, Andrew P.; Gläser, Sven; Hammond, Christopher J.; Burkart, Kristin M.; Beilby, John; Kritchevsky, Stephen B.; Gudnason, Vilmundur; Hancock, Dana B.; Williams, O. Dale; Polasek, Ozren; Zemunik, Tatijana; Kolcic, Ivana; Petrini, Marcy F.; Wjst, Matthias; Kim, Woo Jin; Porteous, David J.; Scotland, Generation; Smith, Blair H.; Viljanen, Anne; Heliövaara, Markku; Attia, John R.; Sayers, Ian; Hampel, Regina; Gieger, Christian; Deary, Ian J.; Boezen, H. Marike; Newman, Anne; Jarvelin, Marjo Riitta; Wilson, James F.; Lind, Lars; Stricker, Bruno H.; Teumer, Alexander; Spector, Timothy D.; Melén, Erik; Peters, Marjolein J.; Lange, Leslie A.; Barr, R. Graham; Bracke, Ken R.; Verhamme, Fien M.; Sung, Joohon; Hiemstra, Pieter S.; Cassano, Patricia A.; Sood, Akshay; Hayward, Caroline; Dupuis, Josée; Hall, Ian P.; Brusselle, Guy G.; Tobin, Martin D.; London, Stephanie J.

In: Nature Genetics, Vol. 46, No. 7, 07.2014, p. 669-677.

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

TY - JOUR

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

AU - Loth, Daan W.

AU - Artigas, María 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 - Kumar, Rajesh

AU - Pin, Isabelle

AU - Scott, Robert A.

AU - Pietiläinen, Kirsi H.

AU - Surakka, Ida

AU - Liu, Yongmei

AU - Holliday, Elizabeth G.

AU - Schulz, Holger

AU - Heinrich, Joachim

AU - Davies, Gail

AU - Vonk, Judith M.

AU - Wojczynski, Mary

AU - Pouta, Anneli

AU - Johansson, Asa

AU - Wild, Sarah H.

AU - Ingelsson, Erik

AU - Rivadeneira, Fernando

AU - Völzke, Henry

AU - Hysi, Pirro G.

AU - Eiriksdottir, Gudny

AU - Morrison, Alanna C.

AU - Rotter, Jerome I.

AU - Gao, Wei

AU - Postma, Dirkje S.

AU - White, Wendy B.

AU - Rich, Stephen S.

AU - Hofman, Albert

AU - Aspelund, Thor

AU - Couper, David

AU - Smith, Lewis J.

AU - Psaty, Bruce M.

AU - Lohman, Kurt

AU - Burchard, Esteban G.

AU - Uitterlinden, André G.

AU - Garcia, Melissa

AU - Joubert, Bonnie R.

AU - McArdle, Wendy L.

AU - Musk, A. Bill

AU - Hansel, Nadia

AU - Heckbert, Susan R.

AU - Zgaga, Lina

AU - Van Meurs, Joyce B.J.

AU - Navarro, Pau

AU - Rudan, Igor

AU - Oh, Yeon Mok

AU - Redline, Susan

AU - Jarvis, Deborah L.

AU - Zhao, Jing Hua

AU - Rantanen, Taina

AU - O'Connor, George T.

AU - Ripatti, Samuli

AU - Scott, Rodney J.

AU - Karrasch, Stefan

AU - Grallert, Harald

AU - Gaddis, Nathan C.

AU - Starr, John M.

AU - Wijmenga, Cisca

AU - Minster, Ryan L.

AU - Lederer, David J.

AU - Pekkanen, Juha

AU - Gyllensten, Ulf

AU - Campbell, Harry

AU - Morris, Andrew P.

AU - Gläser, Sven

AU - Hammond, Christopher J.

AU - Burkart, Kristin M.

AU - Beilby, John

AU - Kritchevsky, Stephen B.

AU - Gudnason, Vilmundur

AU - Hancock, Dana B.

AU - Williams, O. Dale

AU - Polasek, Ozren

AU - Zemunik, Tatijana

AU - Kolcic, Ivana

AU - Petrini, Marcy F.

AU - Wjst, Matthias

AU - Kim, Woo Jin

AU - Porteous, David J.

AU - Scotland, Generation

AU - Smith, Blair H.

AU - Viljanen, Anne

AU - Heliövaara, Markku

AU - Attia, John R.

AU - Sayers, Ian

AU - Hampel, Regina

AU - Gieger, Christian

AU - Deary, Ian J.

AU - Boezen, H. Marike

AU - Newman, Anne

AU - Jarvelin, Marjo Riitta

AU - Wilson, James F.

AU - Lind, Lars

AU - Stricker, Bruno H.

AU - Teumer, Alexander

AU - Spector, Timothy D.

AU - Melén, Erik

AU - Peters, Marjolein J.

AU - Lange, Leslie A.

AU - Barr, R. Graham

AU - Bracke, Ken R.

AU - Verhamme, Fien M.

AU - Sung, Joohon

AU - Hiemstra, Pieter S.

AU - Cassano, Patricia A.

AU - Sood, Akshay

AU - Hayward, Caroline

AU - Dupuis, Josée

AU - Hall, Ian P.

AU - Brusselle, Guy G.

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 × 10-8) 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84903637201&partnerID=8YFLogxK

U2 - 10.1038/ng.3011

DO - 10.1038/ng.3011

M3 - Article

C2 - 24929828

AN - SCOPUS:84903637201

VL - 46

SP - 669

EP - 677

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -

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

Abstract

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