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

Loth, Daan W.; Artigas, Mar�a 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; K�h�nen, 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; Vi�uela, 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.; Pietil�inen, Kirsi H.; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G.; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M.; Wojczynski, Mary; Pouta, Anneli; Johansson, �sa; Wild, Sarah H.; Ingelsson, Erik; Rivadeneira, Fernando; V�lzke, 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, Andr� 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.; Gl�ser, 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.; Smith, Blair H.; Viljanen, Anne; Heli�vaara, 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.; Mel�n, 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, Jos�e; Hall, Ian P.; Brusselle, Guy G.; Tobin, Martin D.; London, Stephanie J.

doi:10.1038/ng.3011

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

Loth, Daan W.; Artigas, Mar?a 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; K?h?nen, 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; Vi?uela, 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.; Pietil?inen, Kirsi H.; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G.; Schulz, Holger; Heinrich, Joachim;...

Authors

Daan W. Loth

Mar�a 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 K�h�nen

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 Vi�uela

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. Pietil�inen

Ida Surakka

Yongmei Liu

Elizabeth G. Holliday

Holger Schulz

Joachim Heinrich

Gail Davies

Judith M. Vonk

Mary Wojczynski

Anneli Pouta

�sa Johansson

Sarah H. Wild

Erik Ingelsson

Fernando Rivadeneira

Henry V�lzke

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

Andr� 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 Gl�ser

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

Blair H. Smith

Anne Viljanen

Markku Heli�vaara

John R. Attia

Professor IAN SAYERS ian.sayers@nottingham.ac.uk
Professor of Respiratory Molecular Genetics

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 Mel�n

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

Jos�e Dupuis

IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine

Guy G. Brusselle

Martin D. Tobin

Stephanie J. London

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.

Citation

Loth, D. W., Artigas, M. S., Gharib, S. A., Wain, L. V., Franceschini, N., Koch, B., …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

Journal Article Type	Article
Acceptance Date	May 22, 2014
Online Publication Date	Jun 15, 2014
Publication Date	Jun 15, 2014
Deposit Date	Apr 5, 2016
Publicly Available Date	Apr 5, 2016
Journal	Nature Genetics
Print ISSN	1061-4036
Electronic ISSN	1546-1718
Publisher	Nature Publishing Group
Peer Reviewed	Peer Reviewed
Volume	46
Issue	7
Pages	669-677
DOI	https://doi.org/10.1038/ng.3011
Keywords	Genetics research, Genome-wide association studies, Population genetics, Respiratory tract diseases
Public URL	https://nottingham-repository.worktribe.com/output/995024
Publisher URL	https://www.nature.com/articles/ng.3011