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

Autor: George T. O'Connor, Natalie Terzikhan, Albert V. Smith, Georg Homuth, Nick Shrine, Raymond Noordam, Stephen B. Kritchevsky, Patricia A. Cassano, Matthias Wielscher, Tobias Bonten, Yongmei Liu, Kurt Lohman, Traci M. Bartz, Elizabeth C. Oelsner, John M. Starr, Sarah E. Harris, Ani Manichaikul, Stefan Weiss, Lies Lahousse, Stefan Karrasch, Tianzhong Yang, Josée Dupuis, Alanna C. Morrison, Holger Schulz, Stephen S. Rich, Han Chen, Ian P. Hall, Sven Gläser, Sina A. Gharib, Victoria E. Jackson, Christian Gieger, Kent D. Taylor, Ruifang Li-Gao, Marjo-Riitta Järvelin, Annette Peters, Ralf Ewert, Bruce M. Psaty, Dennis O. Mook-Kanamori, Peng Wei, Ian J. Deary, Guy Brusselle, Jiayi Xu, Claudia Flexeder, Stephanie J. London, R. G. Barr, Colleen M. Sitlani, Martin D. Tobin
Přispěvatelé: Epidemiology
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, 11(1):19365. Nature Publishing Group
Yang, T, Jackson, V E, Smith, A V, Chen, H, Bartz, T M, Sitlani, C M, Psaty, B M, Gharib, S A, O’connor, G T, Dupuis, J, Xu, J, Lohman, K, Liu, Y, Kritchevsky, S B, Cassano, P A, Flexeder, C, Gieger, C, Karrasch, S, Peters, A, Schulz, H, Harris, S E, Starr, J M, Deary, I J, Manichaikul, A, Oelsner, E C, Barr, R G, Taylor, K D, Rich, S S, Bonten, T N, Mook-kanamori, D O, 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, I P, Tobin, M, London, S J, Wei, P & Morrison, A C 2021, ' Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function ', Scientific Reports, vol. 11, no. 1 . https://doi.org/10.1038/s41598-021-98120-7
SCIENTIFIC REPORTS
Scientific Reports, 11(1). NATURE PORTFOLIO
Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-021-98120-7
Popis: 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.
Databáze: OpenAIRE
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