Genome-wide association study of lung function phenotypes in a founder population

Tsung Chieh Yao, Gaixin Du, Lide Han, Ying Sun, Donglei Hu, James J. Yang, Rasika Mathias, Lindsey A. Roth, Nicholas Rafaels, Emma E. Thompson, Dagan A. Loisel, Rebecca Anderson, Celeste Eng, Maitane Arruabarrena Orbegozo, Melody Young, James M. Klocksieben, Elizabeth Anderson, Kathleen Shanovich, Lucille A. Lester, L. Keoki Williams & 5 others Kathleen C. Barnes, Esteban G. Burchard, Dan L. Nicolae, Mark Abney, Carole Ober

Research output: Contribution to journalArticle

Abstract

Background Lung function is a long-term predictor of mortality and morbidity. Objective We sought to identify single nucleotide polymorphisms (SNPs) associated with lung function. Methods We performed a genome-wide association study (GWAS) of FEV1, forced vital capacity (FVC), and FEV1/FVC in 1144 Hutterites aged 6 to 89 years, who are members of a founder population of European descent. We performed least absolute shrinkage and selection operation regression to select the minimum set of SNPs that best predict FEV1/FVC in the Hutterites and used the GRAIL algorithm to mine the Gene Ontology database for evidence of functional connections between genes near the predictive SNPs. Results Our GWAS identified significant associations between FEV1/FVC and SNPs at the THSD4-UACA-TLE3 locus on chromosome 15q23 (P = 5.7 × 10-8 to 3.4 × 10 -9). Nine SNPs at or near 4 additional loci had P <10 -5 with FEV1/FVC. Only 2 SNPs were found with P <10-5 for FEV1 or FVC. We found nominal levels of significance with SNPs at 9 of the 27 previously reported loci associated with lung function measures. Among a predictive set of 80 SNPs, 6 loci were identified that had a significant degree of functional connectivity (GRAIL P

Original languageEnglish (US)
JournalThe Journal of Allergy and Clinical Immunology
Volume133
Issue number1
DOIs
StatePublished - Jan 2014

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Genome-Wide Association Study
Single Nucleotide Polymorphism
Vital Capacity
Phenotype
Lung
Population
Gene Ontology
Chromosomes
Databases
Morbidity
Mortality
Genes

Keywords

  • FEV
  • FEV/FVC
  • FVC
  • GRAIL
  • GWAS
  • LASSO regression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Genome-wide association study of lung function phenotypes in a founder population. / Yao, Tsung Chieh; Du, Gaixin; Han, Lide; Sun, Ying; Hu, Donglei; Yang, James J.; Mathias, Rasika; Roth, Lindsey A.; Rafaels, Nicholas; Thompson, Emma E.; Loisel, Dagan A.; Anderson, Rebecca; Eng, Celeste; Arruabarrena Orbegozo, Maitane; Young, Melody; Klocksieben, James M.; Anderson, Elizabeth; Shanovich, Kathleen; Lester, Lucille A.; Williams, L. Keoki; Barnes, Kathleen C.; Burchard, Esteban G.; Nicolae, Dan L.; Abney, Mark; Ober, Carole.

In: The Journal of Allergy and Clinical Immunology, Vol. 133, No. 1, 01.2014.

Research output: Contribution to journalArticle

Yao, TC, Du, G, Han, L, Sun, Y, Hu, D, Yang, JJ, Mathias, R, Roth, LA, Rafaels, N, Thompson, EE, Loisel, DA, Anderson, R, Eng, C, Arruabarrena Orbegozo, M, Young, M, Klocksieben, JM, Anderson, E, Shanovich, K, Lester, LA, Williams, LK, Barnes, KC, Burchard, EG, Nicolae, DL, Abney, M & Ober, C 2014, 'Genome-wide association study of lung function phenotypes in a founder population', The Journal of Allergy and Clinical Immunology, vol. 133, no. 1. https://doi.org/10.1016/j.jaci.2013.06.018
Yao, Tsung Chieh ; Du, Gaixin ; Han, Lide ; Sun, Ying ; Hu, Donglei ; Yang, James J. ; Mathias, Rasika ; Roth, Lindsey A. ; Rafaels, Nicholas ; Thompson, Emma E. ; Loisel, Dagan A. ; Anderson, Rebecca ; Eng, Celeste ; Arruabarrena Orbegozo, Maitane ; Young, Melody ; Klocksieben, James M. ; Anderson, Elizabeth ; Shanovich, Kathleen ; Lester, Lucille A. ; Williams, L. Keoki ; Barnes, Kathleen C. ; Burchard, Esteban G. ; Nicolae, Dan L. ; Abney, Mark ; Ober, Carole. / Genome-wide association study of lung function phenotypes in a founder population. In: The Journal of Allergy and Clinical Immunology. 2014 ; Vol. 133, No. 1.
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AU - Yao, Tsung Chieh

AU - Du, Gaixin

AU - Han, Lide

AU - Sun, Ying

AU - Hu, Donglei

AU - Yang, James J.

AU - Mathias, Rasika

AU - Roth, Lindsey A.

AU - Rafaels, Nicholas

AU - Thompson, Emma E.

AU - Loisel, Dagan A.

AU - Anderson, Rebecca

AU - Eng, Celeste

AU - Arruabarrena Orbegozo, Maitane

AU - Young, Melody

AU - Klocksieben, James M.

AU - Anderson, Elizabeth

AU - Shanovich, Kathleen

AU - Lester, Lucille A.

AU - Williams, L. Keoki

AU - Barnes, Kathleen C.

AU - Burchard, Esteban G.

AU - Nicolae, Dan L.

AU - Abney, Mark

AU - Ober, Carole

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N2 - Background Lung function is a long-term predictor of mortality and morbidity. Objective We sought to identify single nucleotide polymorphisms (SNPs) associated with lung function. Methods We performed a genome-wide association study (GWAS) of FEV1, forced vital capacity (FVC), and FEV1/FVC in 1144 Hutterites aged 6 to 89 years, who are members of a founder population of European descent. We performed least absolute shrinkage and selection operation regression to select the minimum set of SNPs that best predict FEV1/FVC in the Hutterites and used the GRAIL algorithm to mine the Gene Ontology database for evidence of functional connections between genes near the predictive SNPs. Results Our GWAS identified significant associations between FEV1/FVC and SNPs at the THSD4-UACA-TLE3 locus on chromosome 15q23 (P = 5.7 × 10-8 to 3.4 × 10 -9). Nine SNPs at or near 4 additional loci had P <10 -5 with FEV1/FVC. Only 2 SNPs were found with P <10-5 for FEV1 or FVC. We found nominal levels of significance with SNPs at 9 of the 27 previously reported loci associated with lung function measures. Among a predictive set of 80 SNPs, 6 loci were identified that had a significant degree of functional connectivity (GRAIL P

AB - Background Lung function is a long-term predictor of mortality and morbidity. Objective We sought to identify single nucleotide polymorphisms (SNPs) associated with lung function. Methods We performed a genome-wide association study (GWAS) of FEV1, forced vital capacity (FVC), and FEV1/FVC in 1144 Hutterites aged 6 to 89 years, who are members of a founder population of European descent. We performed least absolute shrinkage and selection operation regression to select the minimum set of SNPs that best predict FEV1/FVC in the Hutterites and used the GRAIL algorithm to mine the Gene Ontology database for evidence of functional connections between genes near the predictive SNPs. Results Our GWAS identified significant associations between FEV1/FVC and SNPs at the THSD4-UACA-TLE3 locus on chromosome 15q23 (P = 5.7 × 10-8 to 3.4 × 10 -9). Nine SNPs at or near 4 additional loci had P <10 -5 with FEV1/FVC. Only 2 SNPs were found with P <10-5 for FEV1 or FVC. We found nominal levels of significance with SNPs at 9 of the 27 previously reported loci associated with lung function measures. Among a predictive set of 80 SNPs, 6 loci were identified that had a significant degree of functional connectivity (GRAIL P

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