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Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function.

Publication ,  Journal Article
Yang, T; Jackson, VE; Smith, AV; Chen, H; Bartz, TM; Sitlani, CM; Psaty, BM; Gharib, SA; O'Connor, GT; Dupuis, J; Xu, J; Lohman, K; Liu, Y ...
Published in: Sci Rep
September 29, 2021

Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV1. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 29, 2021

Volume

11

Issue

1

Start / End Page

19365

Location

England

Related Subject Headings

  • Risk Factors
  • Receptors, G-Protein-Coupled
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Lung
  • Humans
  • Genome-Wide Association Study
  • Gene-Environment Interaction
  • Forced Expiratory Volume
 

Citation

APA
Chicago
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MLA
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Yang, T., Jackson, V. E., Smith, A. V., Chen, H., Bartz, T. M., Sitlani, C. M., … Morrison, A. C. (2021). Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function. Sci Rep, 11(1), 19365. https://doi.org/10.1038/s41598-021-98120-7
Yang, Tianzhong, Victoria E. Jackson, Albert V. Smith, Han Chen, Traci M. Bartz, Colleen M. Sitlani, Bruce M. Psaty, et al. “Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function.Sci Rep 11, no. 1 (September 29, 2021): 19365. https://doi.org/10.1038/s41598-021-98120-7.
Yang T, Jackson VE, Smith AV, Chen H, Bartz TM, Sitlani CM, et al. Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function. Sci Rep. 2021 Sep 29;11(1):19365.
Yang, Tianzhong, et al. “Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function.Sci Rep, vol. 11, no. 1, Sept. 2021, p. 19365. Pubmed, doi:10.1038/s41598-021-98120-7.
Yang T, Jackson VE, Smith AV, Chen H, Bartz TM, Sitlani CM, Psaty BM, Gharib SA, O’Connor GT, Dupuis J, Xu J, Lohman K, Liu Y, Kritchevsky SB, Cassano PA, Flexeder C, Gieger C, Karrasch S, Peters A, Schulz H, Harris SE, Starr JM, Deary IJ, Manichaikul A, Oelsner EC, Barr RG, Taylor KD, Rich SS, Bonten TN, Mook-Kanamori DO, Noordam R, Li-Gao R, Jarvelin M-R, Wielscher M, Terzikhan N, Lahousse L, Brusselle G, Weiss S, Ewert R, Gläser S, Homuth G, Shrine N, Hall IP, Tobin M, London SJ, Wei P, Morrison AC. Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function. Sci Rep. 2021 Sep 29;11(1):19365.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 29, 2021

Volume

11

Issue

1

Start / End Page

19365

Location

England

Related Subject Headings

  • Risk Factors
  • Receptors, G-Protein-Coupled
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Lung
  • Humans
  • Genome-Wide Association Study
  • Gene-Environment Interaction
  • Forced Expiratory Volume