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

by Spector, Timothy D , Morris, Andrew P , Loth, Daan W , O'Connor, George T , Gudnason, Vilmundur , Rotter, Jerome I , Lohman, Kurt , Sayers, Ian , Minster, Ryan L , Harris, Tamara B , Burchard, Esteban G , Franceschini, Nora , White, Wendy B , Fornage, Myriam , Postma, Dirkje S , Hall, Ian P , Zemunik, Tatijana , Morrison, Alanna C , Liu, Yongmei , Zgaga, Lina , Lederer, David J , Garcia, Melissa , Rudan, Igor , Eiriksdottir, Gudny , Gao, Wei , Holliday, Elizabeth G , Gu, Xiangjun , Strachan, David P , Burkart, Kristin M , Trochet, Holly , Kaprio, Jaakko , Williams, O Dale , Smith, Lewis J , Navarro, Pau , Hammond, Christopher J , Pietiläinen, Kirsi H , Wilson, James F , Hayward, Caroline , Wijmenga, Cisca , Uitterlinden, André G , Campbell, Harry , Viljanen, Anne , Vonk, Judith M , Kähönen, Mika , Barr, R Graham , Hastie, Nicholas D , Redline, Susan , Gyllensten, Ulf , Newman, Anne , Tobin, Martin D , Oldmeadow, Chris , Smith, Blair H , Scott, Robert A , Davies, Gail , Lahousse, Lies , Heinrich, Joachim , Lind, Lars , Boezen, H Marike , Joshi, Peter K , Lee, Mi Kyeong , Gieger, Christian , Ramasamy, Adaikalavan , Psaty, Bruce M , Hansel, Nadia , Deary, Ian J , Bracke, Ken R , Hec

in 45/43 / 45/88 / 631/208/205/2138 / 631/208/457 / 692/308/2056 / 692/699/1785 / African Americans / Agriculture / Animal Genetics and Genomics / Biomedicine / Cancer Research / Cohort Studies / Databases, Genetic / Follow-Up Studies / Forced Expiratory Volume / Gene expression / Gene Function / Gene loci / Genealogy / Genetic aspects / Genetic Loci - genetics / Genetic Predisposition to Disease / Genome, Human / Genome-wide association studies / Genome-Wide Association Study / Genomes / Hispanic people / Human Genetics / Humans / Identification and classification / Lung Diseases - genetics / Lung Diseases - pathology / Lungs / Meta-analysis / Meta-Analysis as Topic / Mortality / Physiological aspects / Polymorphism, Single Nucleotide - genetics / Prognosis / Pulmonary function tests / Quantitative trait loci / Quantitative Trait Loci - genetics / Respiratory function / Respiratory Function Tests / Smoking / Spirometry / Studies / Twins / Vital Capacity - genetics

2014

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

2014

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2014

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Journal Article

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

Spector, Timothy D,

Morris, Andrew P,

Loth, Daan W,

O'Connor, George T,

Gudnason, Vilmundur,

Rotter, Jerome I,

Lohman, Kurt,

Sayers, Ian,

Minster, Ryan L,

Harris, Tamara B,

Burchard, Esteban G,

Franceschini, Nora,

White, Wendy B,

Fornage, Myriam,

Postma, Dirkje S,

Hall, Ian P,

Zemunik, Tatijana,

Morrison, Alanna C,

Liu, Yongmei,

Zgaga, Lina,

Lederer, David J,

Garcia, Melissa,

Rudan, Igor,

Eiriksdottir, Gudny,

Gao, Wei,

Holliday, Elizabeth G,

Gu, Xiangjun,

Strachan, David P,

Burkart, Kristin M,

Trochet, Holly,

Kaprio, Jaakko,

Williams, O Dale,

Smith, Lewis J,

Navarro, Pau,

Hammond, Christopher J,

Pietiläinen, Kirsi H,

Wilson, James F,

Hayward, Caroline,

Wijmenga, Cisca,

Uitterlinden, André G,

Campbell, Harry,

Viljanen, Anne,

Vonk, Judith M,

Kähönen, Mika,

Barr, R Graham,

Hastie, Nicholas D,

Redline, Susan,

Gyllensten, Ulf,

Newman, Anne,

Tobin, Martin D,

Oldmeadow, Chris,

Smith, Blair H,

Scott, Robert A,

Davies, Gail,

Lahousse, Lies,

Heinrich, Joachim,

Lind, Lars,

Boezen, H Marike,

Joshi, Peter K,

Lee, Mi Kyeong,

Gieger, Christian,

Ramasamy, Adaikalavan,

Psaty, Bruce M,

Hansel, Nadia,

Deary, Ian J,

Bracke, Ken R,

Hec

2014

Overview

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells. 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.

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