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

Daan Loth; MS Artigas; SA Gharib; LV Wain; N Franceschini; B Koch; TD Pottinger; AV Smith; Q Duan; C Oldmeadow; MK Lee; DP Strachan; AL James; JE Huffman; V Vitart; A Ramasamy; NJ Wareham; J Kaprio; XQ Wang; H Trochet; M Kahonen; C Flexeder; E Albrecht; LM Lopez; Kim Jong; B Thyagarajan; AC Alves; S Enroth; E Omenaas; PK Joshi; T Fall; A Vinuela; LJ (Lenore) Launer; LR Loehr; M Fornage; G Li; JB Wik; WB Tang; A Manichaikul; Lies Lahousse; TB Harris; KE North; AR Rudnicka; J Hui; XJ Gu; T Lumley; AF Wright; ND Hastie; S Campbell; R Kumar; I Pin; RA Scott; KH Pietilainen; I Surakka; YM Liu; EG Holliday; H Schulz; J (Joachim) Heinrich; G Davies; JM Vonk; M Wojczynski; A Pouta; A Johansson; SH Wild; E Ingelsson; Fernando Rivadeneira; H Vozke; PG Hysi; G Eiriksdottir; AC Morrison; JI Rotter; W Gao; DS Postma; WB White; SS Rich; Bert Hofman; T Aspelund; D Couper; LJ Smith; BM Psaty; K Lohman; EG Burchard; André Uitterlinden; M Garcia; BR Joubert; WL McArdle; AB Musk; N Hansel; SR Heckbert; L Zgaga; Joyce van Meurs; P Navarro; I Rudan; YM Oh; S Redline; DL Jarvis; JH Zhao; T Rantanen; GT O'Connor; S Ripatti; RJ Scott; S Karrasch; H Grallert; NC Gaddis; JM Starr; C Wijmenga; RL Minster; DJ Lederer; J Pekkanen; U Gyllensten; H Campbe; AP Morris; S Glaser; CJ Hammond; KM Burkart; J Beilby; SB Kritchevsky; V Gucinason; DB Hancock; D Williams; O Polasek; T Zemunik; I Kolcic; MF Petrini; M Wjst; WJ Kim; DJ Porteous; G Scotland; BH Smith; A Villanen; M Heliovaara; JR Attia; I Sayers; R Hampel; C Gieger; IJ Deary; HM Boezen; A Newman; MR Jarvelin; JF Wilson; L Lind; Bruno Stricker; A Teumer; TD Spector; E Melen; Marjolein Peters; LA Lange; RG Barr; KR Bracke; FM Verhamme; J Sung; PS Hiemstra; PA Cassano; A Sood; C Hayward; J Dupuis; IP Hall; Guy Brusselle; MD Tobin; SJ London

doi:10.1038/ng.3011

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

Daan Loth, MS Artigas, SA Gharib, LV Wain, N Franceschini, B Koch, TD Pottinger, AV Smith, Q Duan, C Oldmeadow, MK Lee, DP Strachan, AL James, JE Huffman, V Vitart, A Ramasamy, NJ Wareham, J Kaprio, XQ Wang, H TrochetM Kahonen, C Flexeder, E Albrecht, LM Lopez, Kim Jong, B Thyagarajan, AC Alves, S Enroth, E Omenaas, PK Joshi, T Fall, A Vinuela, LJ (Lenore) Launer, LR Loehr, M Fornage, G Li, JB Wik, WB Tang, A Manichaikul, Lies Lahousse, TB Harris, KE North, AR Rudnicka, J Hui, XJ Gu, T Lumley, AF Wright, ND Hastie, S Campbell, R Kumar, I Pin, RA Scott, KH Pietilainen, I Surakka, YM Liu, EG Holliday, H Schulz, J (Joachim) Heinrich, G Davies, JM Vonk, M Wojczynski, A Pouta, A Johansson, SH Wild, E Ingelsson, Fernando Rivadeneira, H Vozke, PG Hysi, G Eiriksdottir, AC Morrison, JI Rotter, W Gao, DS Postma, WB White, SS Rich, Bert Hofman, T Aspelund, D Couper, LJ Smith, BM Psaty, K Lohman, EG Burchard, André Uitterlinden, M Garcia, BR Joubert, WL McArdle, AB Musk, N Hansel, SR Heckbert, L Zgaga, Joyce van Meurs, P Navarro, I Rudan, YM Oh, S Redline, DL Jarvis, JH Zhao, T Rantanen, GT O'Connor, S Ripatti, RJ Scott, S Karrasch, H Grallert, NC Gaddis, JM Starr, C Wijmenga, RL Minster, DJ Lederer, J Pekkanen, U Gyllensten, H Campbe, AP Morris, S Glaser, CJ Hammond, KM Burkart, J Beilby, SB Kritchevsky, V Gucinason, DB Hancock, D Williams, O Polasek, T Zemunik, I Kolcic, MF Petrini, M Wjst, WJ Kim, DJ Porteous, G Scotland, BH Smith, A Villanen, M Heliovaara, JR Attia, I Sayers, R Hampel, C Gieger, IJ Deary, HM Boezen, A Newman, MR Jarvelin, JF Wilson, L Lind, Bruno Stricker, A Teumer, TD Spector, E Melen, Marjolein Peters, LA Lange, RG Barr, KR Bracke, FM Verhamme, J Sung, PS Hiemstra, PA Cassano, A Sood, C Hayward, J Dupuis, IP Hall, Guy Brusselle, MD Tobin, SJ London

Research output: Contribution to journal › Article › Academic › 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 x 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	Undefined/Unknown
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 - 2014

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EMC MM-01-39-09-A
EMC NIHES-01-64-03

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

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10.1038/ng.3011

Cite this

Loth, D., 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., ... London, SJ. (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{63ea7f7beb3d4793a19c9b0f51042957,

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 x 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 = "Daan Loth and MS Artigas and SA Gharib and LV Wain and N Franceschini and B Koch and TD Pottinger and AV Smith and Q Duan and C Oldmeadow and MK Lee and DP Strachan and AL James and JE Huffman and V Vitart and A Ramasamy and NJ Wareham and J Kaprio and XQ Wang and H Trochet and M Kahonen and C Flexeder and E Albrecht and LM Lopez and Kim Jong and B Thyagarajan and AC Alves and S Enroth and E Omenaas and PK Joshi and T Fall and A Vinuela and Launer, {LJ (Lenore)} and LR Loehr and M Fornage and G Li and JB Wik and WB Tang and A Manichaikul and Lies Lahousse and TB Harris and KE North and AR Rudnicka and J Hui and XJ Gu and T Lumley and AF Wright and ND Hastie and S Campbell and R Kumar and I Pin and RA Scott and KH Pietilainen and I Surakka and YM Liu and EG Holliday and H Schulz and Heinrich, {J (Joachim)} and G Davies and JM Vonk and M Wojczynski and A Pouta and A Johansson and SH Wild and E Ingelsson and Fernando Rivadeneira and H Vozke and PG Hysi and G Eiriksdottir and AC Morrison and JI Rotter and W Gao and DS Postma and WB White and SS Rich and Bert Hofman and T Aspelund and D Couper and LJ Smith and BM Psaty and K Lohman and EG Burchard and Andr{\'e} Uitterlinden and M Garcia and BR Joubert and WL McArdle and AB Musk and N Hansel and SR Heckbert and L Zgaga and {van Meurs}, Joyce and P Navarro and I Rudan and YM Oh and S Redline and DL Jarvis and JH Zhao and T Rantanen and GT O'Connor and S Ripatti and RJ Scott and S Karrasch and H Grallert and NC Gaddis and JM Starr and C Wijmenga and RL Minster and DJ Lederer and J Pekkanen and U Gyllensten and H Campbe and AP Morris and S Glaser and CJ Hammond and KM Burkart and J Beilby and SB Kritchevsky and V Gucinason and DB Hancock and D Williams and O Polasek and T Zemunik and I Kolcic and MF Petrini and M Wjst and WJ Kim and DJ Porteous and G Scotland and BH Smith and A Villanen and M Heliovaara and JR Attia and I Sayers and R Hampel and C Gieger and IJ Deary and HM Boezen and A Newman and MR Jarvelin and JF Wilson and L Lind and Bruno Stricker and A Teumer and TD Spector and E Melen and Marjolein Peters and LA Lange and RG Barr and KR Bracke and FM Verhamme and J Sung and PS Hiemstra and PA Cassano and A Sood and C Hayward and J Dupuis and IP Hall and Guy Brusselle and MD Tobin and SJ London",

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doi = "10.1038/ng.3011",

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volume = "46",

pages = "669--677",

journal = "Nature Genetics",

issn = "1061-4036",

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Loth, D, 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, Kahonen, M, Flexeder, C, Albrecht, E, Lopez, LM, Jong, K, Thyagarajan, B, Alves, AC, Enroth, S, Omenaas, E, Joshi, PK, Fall, T, Vinuela, A, Launer, LJ, Loehr, LR, Fornage, M, Li, G, Wik, JB, Tang, WB, Manichaikul, A, Lahousse, L, Harris, TB, North, KE, Rudnicka, AR, Hui, J, Gu, XJ, Lumley, T, Wright, AF, Hastie, ND, Campbell, S, Kumar, R, Pin, I, Scott, RA, Pietilainen, KH, Surakka, I, Liu, YM, Holliday, EG, Schulz, H, Heinrich, J, Davies, G, Vonk, JM, Wojczynski, M, Pouta, A, Johansson, A, Wild, SH, Ingelsson, E, Rivadeneira, F, Vozke, H, Hysi, PG, Eiriksdottir, G, Morrison, AC, Rotter, JI, Gao, W, Postma, DS, White, WB, Rich, SS, Hofman, B, Aspelund, T, Couper, D, Smith, LJ, Psaty, BM, Lohman, K, Burchard, EG, Uitterlinden, A, Garcia, M, Joubert, BR, McArdle, WL, Musk, AB, Hansel, N, Heckbert, SR, Zgaga, L, van Meurs, J, 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, Campbe, H, Morris, AP, Glaser, S, Hammond, CJ, Burkart, KM, Beilby, J, Kritchevsky, SB, Gucinason, V, Hancock, DB, Williams, D, Polasek, O, Zemunik, T, Kolcic, I, Petrini, MF, Wjst, M, Kim, WJ, Porteous, DJ, Scotland, G, Smith, BH, Villanen, A, Heliovaara, M, Attia, JR, Sayers, I, Hampel, R, Gieger, C, Deary, IJ, Boezen, HM, Newman, A, Jarvelin, MR, Wilson, JF, Lind, L, Stricker, B, Teumer, A, Spector, TD, Melen, E, Peters, M, Lange, LA, Barr, RG, Bracke, KR, Verhamme, FM, Sung, J, Hiemstra, PS, Cassano, PA, Sood, A, Hayward, C, Dupuis, J, Hall, IP, Brusselle, G, 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

AU - Artigas, MS

AU - Gharib, SA

AU - Wain, LV

AU - Franceschini, N

AU - Koch, B

AU - Pottinger, TD

AU - Smith, AV

AU - Duan, Q

AU - Oldmeadow, C

AU - Lee, MK

AU - Strachan, DP

AU - James, AL

AU - Huffman, JE

AU - Vitart, V

AU - Ramasamy, A

AU - Wareham, NJ

AU - Kaprio, J

AU - Wang, XQ

AU - Trochet, H

AU - Kahonen, M

AU - Flexeder, C

AU - Albrecht, E

AU - Lopez, LM

AU - Jong, Kim

AU - Thyagarajan, B

AU - Alves, AC

AU - Enroth, S

AU - Omenaas, E

AU - Joshi, PK

AU - Fall, T

AU - Vinuela, A

AU - Launer, LJ (Lenore)

AU - Loehr, LR

AU - Fornage, M

AU - Li, G

AU - Wik, JB

AU - Tang, WB

AU - Manichaikul, A

AU - Lahousse, Lies

AU - Harris, TB

AU - North, KE

AU - Rudnicka, AR

AU - Hui, J

AU - Gu, XJ

AU - Lumley, T

AU - Wright, AF

AU - Hastie, ND

AU - Campbell, S

AU - Kumar, R

AU - Pin, I

AU - Scott, RA

AU - Pietilainen, KH

AU - Surakka, I

AU - Liu, YM

AU - Holliday, EG

AU - Schulz, H

AU - Heinrich, J (Joachim)

AU - Davies, G

AU - Vonk, JM

AU - Wojczynski, M

AU - Pouta, A

AU - Johansson, A

AU - Wild, SH

AU - Ingelsson, E

AU - Rivadeneira, Fernando

AU - Vozke, H

AU - Hysi, PG

AU - Eiriksdottir, G

AU - Morrison, AC

AU - Rotter, JI

AU - Gao, W

AU - Postma, DS

AU - White, WB

AU - Rich, SS

AU - Hofman, Bert

AU - Aspelund, T

AU - Couper, D

AU - Smith, LJ

AU - Psaty, BM

AU - Lohman, K

AU - Burchard, EG

AU - Uitterlinden, André

AU - Garcia, M

AU - Joubert, BR

AU - McArdle, WL

AU - Musk, AB

AU - Hansel, N

AU - Heckbert, SR

AU - Zgaga, L

AU - van Meurs, Joyce

AU - Navarro, P

AU - Rudan, I

AU - Oh, YM

AU - Redline, S

AU - Jarvis, DL

AU - Zhao, JH

AU - Rantanen, T

AU - O'Connor, GT

AU - Ripatti, S

AU - Scott, RJ

AU - Karrasch, S

AU - Grallert, H

AU - Gaddis, NC

AU - Starr, JM

AU - Wijmenga, C

AU - Minster, RL

AU - Lederer, DJ

AU - Pekkanen, J

AU - Gyllensten, U

AU - Campbe, H

AU - Morris, AP

AU - Glaser, S

AU - Hammond, CJ

AU - Burkart, KM

AU - Beilby, J

AU - Kritchevsky, SB

AU - Gucinason, V

AU - Hancock, DB

AU - Williams, D

AU - Polasek, O

AU - Zemunik, T

AU - Kolcic, I

AU - Petrini, MF

AU - Wjst, M

AU - Kim, WJ

AU - Porteous, DJ

AU - Scotland, G

AU - Smith, BH

AU - Villanen, A

AU - Heliovaara, M

AU - Attia, JR

AU - Sayers, I

AU - Hampel, R

AU - Gieger, C

AU - Deary, IJ

AU - Boezen, HM

AU - Newman, A

AU - Jarvelin, MR

AU - Wilson, JF

AU - Lind, L

AU - Stricker, Bruno

AU - Teumer, A

AU - Spector, TD

AU - Melen, E

AU - Peters, Marjolein

AU - Lange, LA

AU - Barr, RG

AU - Bracke, KR

AU - Verhamme, FM

AU - Sung, J

AU - Hiemstra, PS

AU - Cassano, PA

AU - Sood, A

AU - Hayward, C

AU - Dupuis, J

AU - Hall, IP

AU - Brusselle, Guy

AU - Tobin, MD

AU - London, SJ

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 x 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 x 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.

U2 - 10.1038/ng.3011

DO - 10.1038/ng.3011

M3 - Article

C2 - 24929828

SN - 1061-4036

VL - 46

SP - 669

EP - 677

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -