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

MS Artigas; Daan Loth; LV Wain; SA Gharib; M Obeidat; WB Tang; GJ Zhai; JH Zhao; AV Smith; JE Huffman; E Albrecht; CM Jackson; DM Evans; G Cadby; M Fornage; A Manichaikul; LM Lopez; T Johnson; MC Aldrich; T Aspelund; I Barroso; H Campbell; PA Cassano; DJ Couper; G Eiriksdottir; N Franceschini; M Garcia; C Gieger; GK Gislason; I Grkovic; CJ Hammond; DB Hancock; TB Harris; A Ramasamy; SR Heckbert; M Heliovaara; G Homuth; PG Hysi; L Alan; S Jankovic; BR Joubert; S Karrasch; N Klopp; B Koch; SB Kritchevsky; LJ (Lenore) Launer; YM Liu; LR Loehr; K Lohman; RJF Loos; T Lumley; KA Al Balushi; WQ Ang; RG Barr; J Beilby; JD Blakey; M Boban; V Boraska; J Brisman; JR Britton; Guy Brusselle; C Cooper; I Curjuric; S Dahgam; IJ Deary; S Ebrahim; Mark Eijgelsheim; C Francks; D Gaysina; R Granell; XJ Gu; JL Hankinson; R Hardy; SE Harris; J Henderson; A Henry; AD Hingorani; Bert Hofman; PG Holt; JN Hui; ML Hunter; M Imboden; KA Jameson; SM Kerr; I Kolcic; F Kronenberg; JZ Liu; J Marchini; T McKeever; AD Morris; AC Olin; DJ Porteous; DS Postma; SS Rich; SM Ring; Fernando Rivadeneira; T Rochat; AA Sayer; I Sayers; PD Sly; GD Smith; A Sood; JM Starr; André Uitterlinden; JM Vonk; SG Wannamethee; PH Whincup; C Wijmenga; OD Williams; A Wong; M Mangino; KD Marciante; WL McArdle; B Meibohm; AC Morrison; KE North; E Omenaas; LJ Palmer; KH Pietilainen; I Pin; O Polasek; A Pouta; BM Psaty; AL Hartikainen; T Rantanen; S Ripatti; JI Rotter; I Rudan; AR Rudnicka; H Schulz; SY Shin; TD Spector; I Surakka; V Vitart; H Volzke; NJ Wareham; NM Warrington; HE Wichmann; SH Wild; JB Wilk; M Wjst; AF Wright; L Zgaga; T Zemunik; CE Pennell; F Nyberg; D Kuh; JW Holloway; HM Boezen; DA Lawlor; RW Morris; N Probst-Hensch; J Kaprio; JF Wilson; C Hayward; M Kahonen; J (Joachim) Heinrich; AW Musk; DL Jarvis; S Glaser; MR Jarvelin; Bruno Stricker; P Elliott; GT O'Connor; DP Strachan; SJ London; IP Hall; V Gudnason; MD Tobin

doi:10.1038/ng.941

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

MS Artigas, Daan Loth, LV Wain, SA Gharib, M Obeidat, WB Tang, GJ Zhai, JH Zhao, AV Smith, JE Huffman, E Albrecht, CM Jackson, DM Evans, G Cadby, M Fornage, A Manichaikul, LM Lopez, T Johnson, MC Aldrich, T AspelundI Barroso, H Campbell, PA Cassano, DJ Couper, G Eiriksdottir, N Franceschini, M Garcia, C Gieger, GK Gislason, I Grkovic, CJ Hammond, DB Hancock, TB Harris, A Ramasamy, SR Heckbert, M Heliovaara, G Homuth, PG Hysi, L Alan, S Jankovic, BR Joubert, S Karrasch, N Klopp, B Koch, SB Kritchevsky, LJ (Lenore) Launer, YM Liu, LR Loehr, K Lohman, RJF Loos, T Lumley, KA Al Balushi, WQ Ang, RG Barr, J Beilby, JD Blakey, M Boban, V Boraska, J Brisman, JR Britton, Guy Brusselle, C Cooper, I Curjuric, S Dahgam, IJ Deary, S Ebrahim, Mark Eijgelsheim, C Francks, D Gaysina, R Granell, XJ Gu, JL Hankinson, R Hardy, SE Harris, J Henderson, A Henry, AD Hingorani, Bert Hofman, PG Holt, JN Hui, ML Hunter, M Imboden, KA Jameson, SM Kerr, I Kolcic, F Kronenberg, JZ Liu, J Marchini, T McKeever, AD Morris, AC Olin, DJ Porteous, DS Postma, SS Rich, SM Ring, Fernando Rivadeneira, T Rochat, AA Sayer, I Sayers, PD Sly, GD Smith, A Sood, JM Starr, André Uitterlinden, JM Vonk, SG Wannamethee, PH Whincup, C Wijmenga, OD Williams, A Wong, M Mangino, KD Marciante, WL McArdle, B Meibohm, AC Morrison, KE North, E Omenaas, LJ Palmer, KH Pietilainen, I Pin, O Polasek, A Pouta, BM Psaty, AL Hartikainen, T Rantanen, S Ripatti, JI Rotter, I Rudan, AR Rudnicka, H Schulz, SY Shin, TD Spector, I Surakka, V Vitart, H Volzke, NJ Wareham, NM Warrington, HE Wichmann, SH Wild, JB Wilk, M Wjst, AF Wright, L Zgaga, T Zemunik, CE Pennell, F Nyberg, D Kuh, JW Holloway, HM Boezen, DA Lawlor, RW Morris, N Probst-Hensch, J Kaprio, JF Wilson, C Hayward, M Kahonen, J (Joachim) Heinrich, AW Musk, DL Jarvis, S Glaser, MR Jarvelin, Bruno Stricker, P Elliott, GT O'Connor, DP Strachan, SJ London, IP Hall, V Gudnason, MD Tobin

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

348 Citations (Scopus)

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	Undefined/Unknown
Pages (from-to)	1082-U70
Journal	Nature Genetics
Volume	43
Issue number	11
DOIs	https://doi.org/10.1038/ng.941
Publication status	Published - 2011

Research programs

EMC MM-01-39-09-A
EMC NIHES-01-64-01

Access to Document

10.1038/ng.941

http://hdl.handle.net/1765/34149

Cite this

Artigas, MS., Loth, D., Wain, LV., Gharib, SA., Obeidat, M., Tang, WB., Zhai, GJ., Zhao, JH., Smith, AV., Huffman, JE., Albrecht, E., Jackson, CM., Evans, DM., Cadby, G., Fornage, M., Manichaikul, A., Lopez, LM., Johnson, T., Aldrich, MC., ... Tobin, MD. (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{4815b31f4c14468a9a3a7222c3ffc487,

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.",

author = "MS Artigas and Daan Loth and LV Wain and SA Gharib and M Obeidat and WB Tang and GJ Zhai and JH Zhao and AV Smith and JE Huffman and E Albrecht and CM Jackson and DM Evans and G Cadby and M Fornage and A Manichaikul and LM Lopez and T Johnson and MC Aldrich and T Aspelund and I Barroso and H Campbell and PA Cassano and DJ Couper and G Eiriksdottir and N Franceschini and M Garcia and C Gieger and GK Gislason and I Grkovic and CJ Hammond and DB Hancock and TB Harris and A Ramasamy and SR Heckbert and M Heliovaara and G Homuth and PG Hysi and L Alan and S Jankovic and BR Joubert and S Karrasch and N Klopp and B Koch and SB Kritchevsky and Launer, {LJ (Lenore)} and YM Liu and LR Loehr and K Lohman and RJF Loos and T Lumley and {Al Balushi}, KA and WQ Ang and RG Barr and J Beilby and JD Blakey and M Boban and V Boraska and J Brisman and JR Britton and Guy Brusselle and C Cooper and I Curjuric and S Dahgam and IJ Deary and S Ebrahim and Mark Eijgelsheim and C Francks and D Gaysina and R Granell and XJ Gu and JL Hankinson and R Hardy and SE Harris and J Henderson and A Henry and AD Hingorani and Bert Hofman and PG Holt and JN Hui and ML Hunter and M Imboden and KA Jameson and SM Kerr and I Kolcic and F Kronenberg and JZ Liu and J Marchini and T McKeever and AD Morris and AC Olin and DJ Porteous and DS Postma and SS Rich and SM Ring and Fernando Rivadeneira and T Rochat and AA Sayer and I Sayers and PD Sly and GD Smith and A Sood and JM Starr and Andr{\'e} Uitterlinden and JM Vonk and SG Wannamethee and PH Whincup and C Wijmenga and OD Williams and A Wong and M Mangino and KD Marciante and WL McArdle and B Meibohm and AC Morrison and KE North and E Omenaas and LJ Palmer and KH Pietilainen and I Pin and O Polasek and A Pouta and BM Psaty and AL Hartikainen and T Rantanen and S Ripatti and JI Rotter and I Rudan and AR Rudnicka and H Schulz and SY Shin and TD Spector and I Surakka and V Vitart and H Volzke and NJ Wareham and NM Warrington and HE Wichmann and SH Wild and JB Wilk and M Wjst and AF Wright and L Zgaga and T Zemunik and CE Pennell and F Nyberg and D Kuh and JW Holloway and HM Boezen and DA Lawlor and RW Morris and N Probst-Hensch and J Kaprio and JF Wilson and C Hayward and M Kahonen and Heinrich, {J (Joachim)} and AW Musk and DL Jarvis and S Glaser and MR Jarvelin and Bruno Stricker and P Elliott and GT O'Connor and DP Strachan and SJ London and IP Hall and V Gudnason and MD Tobin",

year = "2011",

doi = "10.1038/ng.941",

language = "Undefined/Unknown",

volume = "43",

pages = "1082--U70",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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Artigas, MS, Loth, D, Wain, LV, Gharib, SA, Obeidat, M, Tang, WB, Zhai, GJ, 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, Alan, L, Jankovic, S, Joubert, BR, Karrasch, S, Klopp, N, Koch, B, Kritchevsky, SB, Launer, LJ, Liu, YM, Loehr, LR, Lohman, K, Loos, RJF, Lumley, T, Al Balushi, KA, Ang, WQ, Barr, RG, Beilby, J, Blakey, JD, Boban, M, Boraska, V, Brisman, J, Britton, JR, Brusselle, G, Cooper, C, Curjuric, I, Dahgam, S, Deary, IJ, Ebrahim, S, Eijgelsheim, M, Francks, C, Gaysina, D, Granell, R, Gu, XJ, Hankinson, JL, Hardy, R, Harris, SE, Henderson, J, Henry, A, Hingorani, AD, Hofman, B, Holt, PG, Hui, JN, Hunter, ML, Imboden, M, Jameson, KA, Kerr, SM, Kolcic, I, Kronenberg, F, Liu, JZ, Marchini, J, McKeever, T, Morris, AD, Olin, AC, Porteous, DJ, Postma, DS, Rich, SS, Ring, SM, Rivadeneira, F, Rochat, T, Sayer, AA, Sayers, I, Sly, PD, Smith, GD, Sood, A, Starr, JM, Uitterlinden, A, Vonk, JM, Wannamethee, SG, Whincup, PH, Wijmenga, C, Williams, OD, Wong, A, Mangino, M, Marciante, KD, McArdle, WL, Meibohm, B, Morrison, AC, North, KE, Omenaas, E, Palmer, LJ, Pietilainen, KH, Pin, I, Polasek, O, Pouta, A, Psaty, BM, Hartikainen, AL, Rantanen, T, Ripatti, S, Rotter, JI, Rudan, I, Rudnicka, AR, Schulz, H, Shin, SY, Spector, TD, Surakka, I, Vitart, V, Volzke, H, Wareham, NJ, Warrington, NM, Wichmann, HE, Wild, SH, Wilk, JB, Wjst, M, Wright, AF, Zgaga, L, Zemunik, T, Pennell, CE, Nyberg, F, Kuh, D, Holloway, JW, Boezen, HM, Lawlor, DA, Morris, RW, Probst-Hensch, N, Kaprio, J, Wilson, JF, Hayward, C, Kahonen, M, Heinrich, J, Musk, AW, Jarvis, DL, Glaser, S, Jarvelin, MR, Stricker, B, Elliott, P, O'Connor, GT, Strachan, DP, London, SJ, Hall, IP, Gudnason, V & Tobin, MD 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, MS

AU - Loth, Daan

AU - Wain, LV

AU - Gharib, SA

AU - Obeidat, M

AU - Tang, WB

AU - Zhai, GJ

AU - Zhao, JH

AU - Smith, AV

AU - Huffman, JE

AU - Albrecht, E

AU - Jackson, CM

AU - Evans, DM

AU - Cadby, G

AU - Fornage, M

AU - Manichaikul, A

AU - Lopez, LM

AU - Johnson, T

AU - Aldrich, MC

AU - Aspelund, T

AU - Barroso, I

AU - Campbell, H

AU - Cassano, PA

AU - Couper, DJ

AU - Eiriksdottir, G

AU - Franceschini, N

AU - Garcia, M

AU - Gieger, C

AU - Gislason, GK

AU - Grkovic, I

AU - Hammond, CJ

AU - Hancock, DB

AU - Harris, TB

AU - Ramasamy, A

AU - Heckbert, SR

AU - Heliovaara, M

AU - Homuth, G

AU - Hysi, PG

AU - Alan, L

AU - Jankovic, S

AU - Joubert, BR

AU - Karrasch, S

AU - Klopp, N

AU - Koch, B

AU - Kritchevsky, SB

AU - Launer, LJ (Lenore)

AU - Liu, YM

AU - Loehr, LR

AU - Lohman, K

AU - Loos, RJF

AU - Lumley, T

AU - Al Balushi, KA

AU - Ang, WQ

AU - Barr, RG

AU - Beilby, J

AU - Blakey, JD

AU - Boban, M

AU - Boraska, V

AU - Brisman, J

AU - Britton, JR

AU - Brusselle, Guy

AU - Cooper, C

AU - Curjuric, I

AU - Dahgam, S

AU - Deary, IJ

AU - Ebrahim, S

AU - Eijgelsheim, Mark

AU - Francks, C

AU - Gaysina, D

AU - Granell, R

AU - Gu, XJ

AU - Hankinson, JL

AU - Hardy, R

AU - Harris, SE

AU - Henderson, J

AU - Henry, A

AU - Hingorani, AD

AU - Hofman, Bert

AU - Holt, PG

AU - Hui, JN

AU - Hunter, ML

AU - Imboden, M

AU - Jameson, KA

AU - Kerr, SM

AU - Kolcic, I

AU - Kronenberg, F

AU - Liu, JZ

AU - Marchini, J

AU - McKeever, T

AU - Morris, AD

AU - Olin, AC

AU - Porteous, DJ

AU - Postma, DS

AU - Rich, SS

AU - Ring, SM

AU - Rivadeneira, Fernando

AU - Rochat, T

AU - Sayer, AA

AU - Sayers, I

AU - Sly, PD

AU - Smith, GD

AU - Sood, A

AU - Starr, JM

AU - Uitterlinden, André

AU - Vonk, JM

AU - Wannamethee, SG

AU - Whincup, PH

AU - Wijmenga, C

AU - Williams, OD

AU - Wong, A

AU - Mangino, M

AU - Marciante, KD

AU - McArdle, WL

AU - Meibohm, B

AU - Morrison, AC

AU - North, KE

AU - Omenaas, E

AU - Palmer, LJ

AU - Pietilainen, KH

AU - Pin, I

AU - Polasek, O

AU - Pouta, A

AU - Psaty, BM

AU - Hartikainen, AL

AU - Rantanen, T

AU - Ripatti, S

AU - Rotter, JI

AU - Rudan, I

AU - Rudnicka, AR

AU - Schulz, H

AU - Shin, SY

AU - Spector, TD

AU - Surakka, I

AU - Vitart, V

AU - Volzke, H

AU - Wareham, NJ

AU - Warrington, NM

AU - Wichmann, HE

AU - Wild, SH

AU - Wilk, JB

AU - Wjst, M

AU - Wright, AF

AU - Zgaga, L

AU - Zemunik, T

AU - Pennell, CE

AU - Nyberg, F

AU - Kuh, D

AU - Holloway, JW

AU - Boezen, HM

AU - Lawlor, DA

AU - Morris, RW

AU - Probst-Hensch, N

AU - Kaprio, J

AU - Wilson, JF

AU - Hayward, C

AU - Kahonen, M

AU - Heinrich, J (Joachim)

AU - Musk, AW

AU - Jarvis, DL

AU - Glaser, S

AU - Jarvelin, MR

AU - Stricker, Bruno

AU - Elliott, P

AU - O'Connor, GT

AU - Strachan, DP

AU - London, SJ

AU - Hall, IP

AU - Gudnason, V

AU - Tobin, MD

PY - 2011

Y1 - 2011

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.

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 -