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Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank.

Wain LV, Shrine N, Miller S, Jackson VE, Ntalla I, Artigas MS, Billington CK, Kheirallah AK, Allen R, Cook JP, Probert K, Obeidat M, Bossé Y, Hao K, Postma DS, Paré PD, Ramasamy A, UK Brain Expression Consortium (UKBEC)Mägi R, Mihailov E, Reinmaa E, Melén E, O'Connell J, Frangou E, Delaneau O, OxGSK ConsortiumFreeman C, Petkova D, McCarthy M, Sayers I, Deloukas P, Hubbard R, Pavord I, Hansell AL, Thomson NC, Zeggini E, Morris AP, Marchini J, Strachan DP, Tobin MD, Hall IP - Lancet Respir Med (2015)

Bottom Line: We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.Medical Research Council.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.

No MeSH data available.


Related in: MedlinePlus

Polygenic component of low forced expiratory volume in 1 s and shared polygenic component of different phenotypes defined by forced expiratory volume in 1 s, smoking, and doctor diagnosis of asthmaThe p value in the target population shown above the bars is for the p value threshold <0·5. The sample sizes differed between the comparisons; details of these and the assumptions used in the analyses are described in the appendix (pp 18–20). FEV1=forced expiratory volume in 1 s.
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fig2: Polygenic component of low forced expiratory volume in 1 s and shared polygenic component of different phenotypes defined by forced expiratory volume in 1 s, smoking, and doctor diagnosis of asthmaThe p value in the target population shown above the bars is for the p value threshold <0·5. The sample sizes differed between the comparisons; details of these and the assumptions used in the analyses are described in the appendix (pp 18–20). FEV1=forced expiratory volume in 1 s.

Mentions: Using independent discovery and target subpopulations to generate and test risk scores, we found that the association of low FEV1 versus average FEV1 with the risk score became stronger for increasingly liberal p value thresholds of association in the discovery population (p=6·24 × 10−16 for a p value threshold of 0·5). This finding suggests a polygenic component to low FEV1, in which many variants of individually small effect size contribute to the risk of low FEV1. We found substantial sharing of genetic causes across thousands of genetic variants between low FEV1 in heavy smokers and low FEV1 in never smokers (p=2·29 × 10−16; p value threshold <0·5; figure 2; appendix p 30). Similarly, we found substantially overlapping genetic causes for low FEV1 in participants reporting a history of doctor-diagnosed asthma and low FEV1 in those without asthma (p=6·06 × 10−11; p value threshold <0·5; figure 2; appendix p 31). Finally, overlapping genetic causes were shown for high FEV1 and low FEV1 (p=1·64 × 10−22; p value threshold <0·5; figure 2; appendix p 30).


Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank.

Wain LV, Shrine N, Miller S, Jackson VE, Ntalla I, Artigas MS, Billington CK, Kheirallah AK, Allen R, Cook JP, Probert K, Obeidat M, Bossé Y, Hao K, Postma DS, Paré PD, Ramasamy A, UK Brain Expression Consortium (UKBEC)Mägi R, Mihailov E, Reinmaa E, Melén E, O'Connell J, Frangou E, Delaneau O, OxGSK ConsortiumFreeman C, Petkova D, McCarthy M, Sayers I, Deloukas P, Hubbard R, Pavord I, Hansell AL, Thomson NC, Zeggini E, Morris AP, Marchini J, Strachan DP, Tobin MD, Hall IP - Lancet Respir Med (2015)

Polygenic component of low forced expiratory volume in 1 s and shared polygenic component of different phenotypes defined by forced expiratory volume in 1 s, smoking, and doctor diagnosis of asthmaThe p value in the target population shown above the bars is for the p value threshold <0·5. The sample sizes differed between the comparisons; details of these and the assumptions used in the analyses are described in the appendix (pp 18–20). FEV1=forced expiratory volume in 1 s.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4593935&req=5

fig2: Polygenic component of low forced expiratory volume in 1 s and shared polygenic component of different phenotypes defined by forced expiratory volume in 1 s, smoking, and doctor diagnosis of asthmaThe p value in the target population shown above the bars is for the p value threshold <0·5. The sample sizes differed between the comparisons; details of these and the assumptions used in the analyses are described in the appendix (pp 18–20). FEV1=forced expiratory volume in 1 s.
Mentions: Using independent discovery and target subpopulations to generate and test risk scores, we found that the association of low FEV1 versus average FEV1 with the risk score became stronger for increasingly liberal p value thresholds of association in the discovery population (p=6·24 × 10−16 for a p value threshold of 0·5). This finding suggests a polygenic component to low FEV1, in which many variants of individually small effect size contribute to the risk of low FEV1. We found substantial sharing of genetic causes across thousands of genetic variants between low FEV1 in heavy smokers and low FEV1 in never smokers (p=2·29 × 10−16; p value threshold <0·5; figure 2; appendix p 30). Similarly, we found substantially overlapping genetic causes for low FEV1 in participants reporting a history of doctor-diagnosed asthma and low FEV1 in those without asthma (p=6·06 × 10−11; p value threshold <0·5; figure 2; appendix p 31). Finally, overlapping genetic causes were shown for high FEV1 and low FEV1 (p=1·64 × 10−22; p value threshold <0·5; figure 2; appendix p 30).

Bottom Line: We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.Medical Research Council.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.

No MeSH data available.


Related in: MedlinePlus