Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function
Abstract 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...
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Nature Portfolio
2021
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oai:doaj.org-article:622bb4c77e7b41ef8a75042749b5e1662021-12-02T17:18:21ZRare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function10.1038/s41598-021-98120-72045-2322https://doaj.org/article/622bb4c77e7b41ef8a75042749b5e1662021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98120-7https://doaj.org/toc/2045-2322Abstract 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.Tianzhong YangVictoria E. JacksonAlbert V. SmithHan ChenTraci M. BartzColleen M. SitlaniBruce M. PsatySina A. GharibGeorge T. O’ConnorJosée DupuisJiayi XuKurt LohmanYongmei LiuStephen B. KritchevskyPatricia A. CassanoClaudia FlexederChristian GiegerStefan KarraschAnnette PetersHolger SchulzSarah E. HarrisJohn M. StarrIan J. DearyAni ManichaikulElizabeth C. OelsnerR. G. BarrKent D. TaylorStephen S. RichTobias N. BontenDennis O. Mook-KanamoriRaymond NoordamRuifang Li-GaoMarjo-Riitta JarvelinMatthias WielscherNatalie TerzikhanLies LahousseGuy BrusselleStefan WeissRalf EwertSven GläserGeorg HomuthNick ShrineIan P. HallMartin TobinStephanie J. LondonPeng WeiAlanna C. MorrisonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
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DOAJ |
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DOAJ |
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EN |
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Medicine R Science Q |
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Medicine R Science Q Tianzhong Yang Victoria E. Jackson Albert V. Smith Han Chen Traci M. Bartz Colleen M. Sitlani Bruce M. Psaty Sina A. Gharib George T. O’Connor Josée Dupuis Jiayi Xu Kurt Lohman Yongmei Liu Stephen B. Kritchevsky Patricia A. Cassano Claudia Flexeder Christian Gieger Stefan Karrasch Annette Peters Holger Schulz Sarah E. Harris John M. Starr Ian J. Deary Ani Manichaikul Elizabeth C. Oelsner R. G. Barr Kent D. Taylor Stephen S. Rich Tobias N. Bonten Dennis O. Mook-Kanamori Raymond Noordam Ruifang Li-Gao Marjo-Riitta Jarvelin Matthias Wielscher Natalie Terzikhan Lies Lahousse Guy Brusselle Stefan Weiss Ralf Ewert Sven Gläser Georg Homuth Nick Shrine Ian P. Hall Martin Tobin Stephanie J. London Peng Wei Alanna C. Morrison Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function |
| description |
Abstract 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. |
| format |
article |
| author |
Tianzhong Yang Victoria E. Jackson Albert V. Smith Han Chen Traci M. Bartz Colleen M. Sitlani Bruce M. Psaty Sina A. Gharib George T. O’Connor Josée Dupuis Jiayi Xu Kurt Lohman Yongmei Liu Stephen B. Kritchevsky Patricia A. Cassano Claudia Flexeder Christian Gieger Stefan Karrasch Annette Peters Holger Schulz Sarah E. Harris John M. Starr Ian J. Deary Ani Manichaikul Elizabeth C. Oelsner R. G. Barr Kent D. Taylor Stephen S. Rich Tobias N. Bonten Dennis O. Mook-Kanamori Raymond Noordam Ruifang Li-Gao Marjo-Riitta Jarvelin Matthias Wielscher Natalie Terzikhan Lies Lahousse Guy Brusselle Stefan Weiss Ralf Ewert Sven Gläser Georg Homuth Nick Shrine Ian P. Hall Martin Tobin Stephanie J. London Peng Wei Alanna C. Morrison |
| author_facet |
Tianzhong Yang Victoria E. Jackson Albert V. Smith Han Chen Traci M. Bartz Colleen M. Sitlani Bruce M. Psaty Sina A. Gharib George T. O’Connor Josée Dupuis Jiayi Xu Kurt Lohman Yongmei Liu Stephen B. Kritchevsky Patricia A. Cassano Claudia Flexeder Christian Gieger Stefan Karrasch Annette Peters Holger Schulz Sarah E. Harris John M. Starr Ian J. Deary Ani Manichaikul Elizabeth C. Oelsner R. G. Barr Kent D. Taylor Stephen S. Rich Tobias N. Bonten Dennis O. Mook-Kanamori Raymond Noordam Ruifang Li-Gao Marjo-Riitta Jarvelin Matthias Wielscher Natalie Terzikhan Lies Lahousse Guy Brusselle Stefan Weiss Ralf Ewert Sven Gläser Georg Homuth Nick Shrine Ian P. Hall Martin Tobin Stephanie J. London Peng Wei Alanna C. Morrison |
| author_sort |
Tianzhong Yang |
| title |
Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function |
| title_short |
Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function |
| title_full |
Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function |
| title_fullStr |
Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function |
| title_full_unstemmed |
Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function |
| title_sort |
rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/622bb4c77e7b41ef8a75042749b5e166 |
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