Genome-wide association study identifies five loci associated with lung function

Lv, Wain; {Wellcome Trust Case Control Consor, Nshd Resp Study Team}; Zhao, {Jing Hua}; Repapi, Emmanouela; Sayers, Ian; Pr, Burton; Jh, Zhao; Wain, Louise V.; Wain, {Louise; Burton, Paul R.; Burton, {Paul R.}; Johnson, Toby; Je, Huffman; Obeidat, Ma’en; Wl, McArdle; Zhao, Jing Hua; Ar, Rudnicka; Ramasamy, Adaikalavan; Huffman, {Jennifer E.}; Zhai, Guangju; Rj, Loos; Vitart, Veronique; Nj, Wareham; Huffman, Jennifer E.; He, Wichmann; Igl, Wilmar; McArdle, {Wendy L.}; Albrecht, Eva; Al, Hartikainen; Deloukas, Panos; Rudnicka, {Alicja R.}; Henderson, John; Johansson, Åsa; Granell, Raquel; Loos, {Ruth J. F.}; Consortium, Wellcome Trust Case Control; McArdle, Wendy L.; Wareham, {Nicholas J.}; Rudnicka, Alicja R.; Sh, Wild; Barroso, Inês; Surakka, {Ida Liisa}; Loos, Ruth J. F.; Jf, Wilson; Wareham, Nicholas J.; Wichmann, {.-H. Erich}; Mustelin, Linda; Td, Spector; Rantanen, Taina; Af, Wright; Surakka, Ida; Naluai, Åsa Torinsson; Imboden, Medea; Wichmann, He-Erich; At, Naluai; Voelzke, Henry; Wild, {Sarah H.}; Grkovic, Ivica; Ac, Olin; Jankovic, Stipan; Wilson, {James F.}; Zgaga, Lina; Erich Wichmann, H.; Hartikainen, Anna-Liisa; Mn, Cooper; Peltonen, Leena; Al, James; Gyllensten, Ulf; Lj, Palmer; Johansson, Åsa; Spector, {Tim D.}; Zaboli, Ghazal; Ad, Hingorani; Campbell, Harry; Sg, Wannamethee; Wild, Sarah H.; Wright, {Alan F.}; Gläser, Sven; Wilson, James F.; Ph, Whincup; Ripatti, {Samuli Olli}; Homuth, Georg; Völzke, Henry; Gd, Smith; Mangino, Massimo; Soranzo, Nicole; Naluai, {Asa Torinsson}; Spector, Tim D.; Tm, McKeever; Polasek, Ozren; Goya Wannamethee, S.; Rudan, Igor; Cooper, {Matthew N.}; Glaeser, Sven; Davey Smith, George; Wright, Alan F.; Heliövaara, Markku; James, {Alan L.}; Ripatti, Samuli; Pouta, Anneli; Palmer, {Lyle J.}; Naluai, Åsa Torinsson; Id, Pavord; Olin, Anna-Carin; Hingorani, {Aroon D.}; Torén, Kjell; Smith, Gd D.; Cooper, Matthew N.; Wannamethee, {.-S. Goya}; Whincup, {Peter H.}; James, Alan L.; Ak, Macleod; Smith, {George Davey}; Palmer, Lyle J.; Hingorani, Aroon D.; Smith, D. Gd; Wannamethee, Sg Goya; Smith, George Davey; Whincup, Peter H.; Ad, Morris; McKeever, {Tricia M.}; Smith, G. D.; Mckeever, Tricia M.; Pavord, {Ian D.}; Dj, Porteous; Ebrahim, Shah; Pavord, Ian D.; MacLeod, {Andrew K.}; Macleod, Andrew K.; Schulz, S.; Morris, {Andrew D.}; Morris, Andrew D.; Porteous, {David J.}; Porteous, David J.; Jd, Blakey; Cooper, Cyrus; N., Bouatia-Naji; Dennison, Elaine; Team, Nshd Respiratory Study; Shaheen, Seif; Karrasch, Stefan; Jr, Britton; Schnabel, Eva; Rw, Morris; Schulz, Holger; Jw, Holloway; Grallert, Harald; Bouatia-Naji, Nabila; Blakey, {John D.}; Delplanque, Jerome; Da, Lawlor; Nshd, Respiratory Study Team; Froguel, Philippe; Britton, {John R.}; Blakey, John D.; Morris, {Richard W.}; Britton, John R.; Mr, Jarvelin; Morris, Richard W.; Holloway, {John W.}; Lawlor, {Debbie A.}; Nm, Probst Hensch; Holloway, John W.; Lawlor, Debbie A.; Hui, Jennie; Kahonen, Mika; Brown, Matthew A.; Nyberg, Fredrik; Jarvelin, Marjo-Riitta; M., Probst-Hensch N.; Jackson, Cathy; Probst-Hensch, {Nicole M.}; Dm, Evans; Kähönen, Mika; Kaprio, Jaakko; Dp, Strachan; Probst-Hensch, Nicole M.; Evans, {David M.}; Koch, Beate; Ip, Hall; Hayward, Caroline; Strachan, {David P.}; Evans, David M.; Md, Tobin; Elliott, Paul; Hall, {Ian P.}; Strachan, David P.; Consor, Wellcome Trust Case Control; Hall, Ian P.; Bradbury, Linda; Tobin, {Martin D.}; Tobin, Martin D.; Wellcome Trust Case Control Consor, Nshd Resp Study Team

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Louise Wain
Lv et al., 2009

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@article{Lv2009,
  abstract = {Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease. ; This paper was published as Nature Genetics, 2010, 42 (1), pp. 36-44. It is available from http://www.nature.com/ng/journal/v42/n1/abs/ng.501.html. Doi: 10.1038/ng.501},
  author = {Lv, Wain and {Wellcome Trust Case Control Consor, Nshd Resp Study Team} and Zhao, {Jing Hua} and Repapi, Emmanouela and Sayers, Ian and Pr, Burton and Jh, Zhao and Wain, Louise V. and Wain, {Louise and Burton, Paul R. and Burton, {Paul R.} and Johnson, Toby and Je, Huffman and Obeidat, Ma’en and Wl, McArdle and Zhao, Jing Hua and Ar, Rudnicka and Ramasamy, Adaikalavan and Huffman, {Jennifer E.} and Zhai, Guangju and Rj, Loos and Vitart, Veronique and Nj, Wareham and Huffman, Jennifer E. and He, Wichmann and Igl, Wilmar and McArdle, {Wendy L.} and Albrecht, Eva and Al, Hartikainen and Deloukas, Panos and Rudnicka, {Alicja R.} and Henderson, John and Johansson, Åsa and Granell, Raquel and Loos, {Ruth J. F.} and Consortium, Wellcome Trust Case Control and McArdle, Wendy L. and Wareham, {Nicholas J.} and Rudnicka, Alicja R. and Sh, Wild and Barroso, Inês and Surakka, {Ida Liisa} and Loos, Ruth J. F. and Jf, Wilson and Wareham, Nicholas J. and Wichmann, {.-H. Erich} and Mustelin, Linda and Td, Spector and Rantanen, Taina and Af, Wright and Surakka, Ida and Naluai, Åsa Torinsson and Imboden, Medea and Wichmann, He-Erich and At, Naluai and Voelzke, Henry and Wild, {Sarah H.} and Grkovic, Ivica and Ac, Olin and Jankovic, Stipan and Wilson, {James F.} and Zgaga, Lina and Erich Wichmann, H. and Hartikainen, Anna-Liisa and Mn, Cooper and Peltonen, Leena and Al, James and Gyllensten, Ulf and Lj, Palmer and Johansson, Åsa and Spector, {Tim D.} and Zaboli, Ghazal and Ad, Hingorani and Campbell, Harry and Sg, Wannamethee and Wild, Sarah H. and Wright, {Alan F.} and Gläser, Sven and Wilson, James F. and Ph, Whincup and Ripatti, {Samuli Olli} and Homuth, Georg and Völzke, Henry and Gd, Smith and Mangino, Massimo and Soranzo, Nicole and Naluai, {Asa Torinsson} and Spector, Tim D. and Tm, McKeever and Polasek, Ozren and Goya Wannamethee, S. and Rudan, Igor and Cooper, {Matthew N.} and Glaeser, Sven and Davey Smith, George and Wright, Alan F. and Heliövaara, Markku and James, {Alan L.} and Ripatti, Samuli and Pouta, Anneli and Palmer, {Lyle J.} and Naluai, Åsa Torinsson and Id, Pavord and Olin, Anna-Carin and Hingorani, {Aroon D.} and Torén, Kjell and Smith, Gd D. and Cooper, Matthew N. and Wannamethee, {.-S. Goya} and Whincup, {Peter H.} and James, Alan L. and Ak, Macleod and Smith, {George Davey} and Palmer, Lyle J. and Hingorani, Aroon D. and Smith, D. Gd and Wannamethee, Sg Goya and Smith, George Davey and Whincup, Peter H. and Ad, Morris and McKeever, {Tricia M.} and Smith, G. D. and Mckeever, Tricia M. and Pavord, {Ian D.} and Dj, Porteous and Ebrahim, Shah and Pavord, Ian D. and MacLeod, {Andrew K.} and Macleod, Andrew K. and Schulz, S. and Morris, {Andrew D.} and Morris, Andrew D. and Porteous, {David J.} and Porteous, David J. and Jd, Blakey and Cooper, Cyrus and N., Bouatia-Naji and Dennison, Elaine and Team, Nshd Respiratory Study and Shaheen, Seif and Karrasch, Stefan and Jr, Britton and Schnabel, Eva and Rw, Morris and Schulz, Holger and Jw, Holloway and Grallert, Harald and Bouatia-Naji, Nabila and Blakey, {John D.} and Delplanque, Jerome and Da, Lawlor and Nshd, Respiratory Study Team and Froguel, Philippe and Britton, {John R.} and Blakey, John D. and Morris, {Richard W.} and Britton, John R. and Mr, Jarvelin and Morris, Richard W. and Holloway, {John W.} and Lawlor, {Debbie A.} and Nm, Probst Hensch and Holloway, John W. and Lawlor, Debbie A. and Hui, Jennie and Kahonen, Mika and Brown, Matthew A. and Nyberg, Fredrik and Jarvelin, Marjo-Riitta and M., Probst-Hensch N. and Jackson, Cathy and Probst-Hensch, {Nicole M.} and Dm, Evans and Kähönen, Mika and Kaprio, Jaakko and Dp, Strachan and Probst-Hensch, Nicole M. and Evans, {David M.} and Koch, Beate and Ip, Hall and Hayward, Caroline and Strachan, {David P.} and Evans, David M. and Md, Tobin and Elliott, Paul and Hall, {Ian P.} and Strachan, David P. and Consor, Wellcome Trust Case Control and Hall, Ian P. and Bradbury, Linda and Tobin, {Martin D.} and Tobin, Martin D. and Wellcome Trust Case Control Consor, Nshd Resp Study Team},
  doi = {10.1038/ng.501},
  month = {dec},
  title = {Genome-wide association study identifies five loci associated with lung function},
  url = {http://www.nature.com/ng/journal/v42/n1/pdf/ng.501.pdf},
  year = {2009}
}

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Genome-wide association study identifies five loci associated with lung function

Journal article published in 2009 by Wain Lv, Nshd Resp Study Team} {Wellcome Trust Case Control Consor, {Jing Hua} Zhao, Emmanouela Repapi, Ian Sayers, Burton Pr, Zhao Jh, Louise V. Wain

, {Louise Wain, Paul R. Burton, {Paul R.} Burton, Toby Johnson

, Huffman Je, Ma’en Obeidat, McArdle Wl and other authors. Wain Lv, Nshd Resp Study Team} {Wellcome Trust Case Control Consor, {Jing Hua} Zhao, Emmanouela Repapi, Ian Sayers, Burton Pr, Zhao Jh, Louise V. Wain

, {Louise Wain, Paul R. Burton, {Paul R.} Burton, Toby Johnson

, Huffman Je, Ma’en Obeidat, McArdle Wl, Jing Hua Zhao, Rudnicka Ar, Adaikalavan Ramasamy, {Jennifer E.} Huffman, Guangju Zhai, Loos Rj, Veronique Vitart, Wareham Nj, Jennifer E. Huffman, Wichmann He, Wilmar Igl, {Wendy L.} McArdle, Eva Albrecht, Hartikainen Al, Panos Deloukas

, {Alicja R.} Rudnicka, John Henderson, Åsa Johansson, Raquel Granell

, {Ruth J. F.} Loos, Wellcome Trust Case Control Consortium, Wendy L. McArdle, {Nicholas J.} Wareham, Alicja R. Rudnicka

, Wild Sh, Inês Barroso, {Ida Liisa} Surakka, Ruth J. F. Loos, Wilson Jf, Nicholas J. Wareham, {.-H. Erich} Wichmann, Linda Mustelin, Spector Td, Taina Rantanen, Wright Af, Ida Surakka, Åsa Torinsson Naluai, Medea Imboden, He-Erich Wichmann, Naluai At, Henry Voelzke, {Sarah H.} Wild, Ivica Grkovic, Olin Ac, Stipan Jankovic, {James F.} Wilson, Lina Zgaga, H. Erich Wichmann, Anna-Liisa Hartikainen, Cooper Mn, Leena Peltonen, James Al, Ulf Gyllensten, Palmer Lj, Åsa Johansson, {Tim D.} Spector, Ghazal Zaboli, Hingorani Ad, Harry Campbell, Wannamethee Sg, Sarah H. Wild, {Alan F.} Wright, Sven Gläser, James F. Wilson, Whincup Ph, {Samuli Olli} Ripatti, Georg Homuth, Henry Völzke, Smith Gd, Massimo Mangino, Nicole Soranzo, {Asa Torinsson} Naluai, Tim D. Spector, McKeever Tm, Ozren Polasek, S. Goya Wannamethee, Igor Rudan, {Matthew N.} Cooper, Sven Glaeser, George Davey Smith, Alan F. Wright, Markku Heliövaara, {Alan L.} James, Samuli Ripatti, Anneli Pouta, {Lyle J.} Palmer, Åsa Torinsson Naluai

, Pavord Id, Anna-Carin Olin, {Aroon D.} Hingorani, Kjell Torén, Gd D. Smith, Matthew N. Cooper, {.-S. Goya} Wannamethee, {Peter H.} Whincup, Alan L. James, Macleod Ak, {George Davey} Smith, Lyle J. Palmer, Aroon D. Hingorani, D. Gd Smith, Sg Goya Wannamethee

, George Davey Smith, Peter H. Whincup, Morris Ad, {Tricia M.} McKeever, G. D. Smith, Tricia M. Mckeever, {Ian D.} Pavord, Porteous Dj, Shah Ebrahim, Ian D. Pavord, {Andrew K.} MacLeod, Andrew K. Macleod, S. Schulz, {Andrew D.} Morris, Andrew D. Morris, {David J.} Porteous, David J. Porteous, Blakey Jd, Cyrus Cooper, Bouatia-Naji N., Elaine Dennison, Nshd Respiratory Study Team, Seif Shaheen, Stefan Karrasch, Britton Jr, Eva Schnabel, Morris Rw, Holger Schulz, Holloway Jw, Harald Grallert, Nabila Bouatia-Naji, {John D.} Blakey, Jerome Delplanque, Lawlor Da, Respiratory Study Team Nshd, Philippe Froguel, {John R.} Britton, John D. Blakey, {Richard W.} Morris, John R. Britton, Jarvelin Mr, Richard W. Morris, {John W.} Holloway, {Debbie A.} Lawlor, Probst Hensch Nm, John W. Holloway, Debbie A. Lawlor, Jennie Hui, Mika Kahonen, Matthew A. Brown, Fredrik Nyberg, Marjo-Riitta Jarvelin, Probst-Hensch N. M., Cathy Jackson, {Nicole M.} Probst-Hensch, Evans Dm, Mika Kähönen, Jaakko Kaprio

, Strachan Dp, Nicole M. Probst-Hensch, {David M.} Evans, Beate Koch, Hall Ip, Caroline Hayward, {David P.} Strachan, David M. Evans, Tobin Md, Paul Elliott, {Ian P.} Hall, David P. Strachan, Wellcome Trust Case Control Consor, Ian P. Hall, Linda Bradbury, {Martin D.} Tobin, Martin D. Tobin, Nshd Resp Study Team Wellcome Trust Case Control Consor

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Abstract

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease. ; This paper was published as Nature Genetics, 2010, 42 (1), pp. 36-44. It is available from http://www.nature.com/ng/journal/v42/n1/abs/ng.501.html. Doi: 10.1038/ng.501

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Genome-wide association study identifies five loci associated with lung function

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