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Sci Rep. 2017 Dec 4;7(1):16907. doi: 10.1038/s41598-017-16964-4.

Genetic Pleiotropy between Nicotine Dependence and Respiratory Outcomes.

Zhang J1,2, Peng S3,4, Cheng H3,4, Nomura Y5,6, Di Narzo AF7, Hao K8,9,10.

Author information

1
Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
2
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
4
Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Department of Psychology, Queens College & Graduate Center, the City University of New York, New York, NY 10016, USA.
6
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
7
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. dinarzo.antonio@gmail.com.
8
Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China. ke.hao@mssm.edu.
9
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. ke.hao@mssm.edu.
10
Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. ke.hao@mssm.edu.

Abstract

Smoking is a major cause of respiratory conditions. To date, the genetic pleiotropy between smoking behavior and lung function/chronic obstructive pulmonary disease (COPD) have not been systematically explored. We leverage large data sets of smoking behavior, lung function and COPD, and addressed two questions, (1) whether the genetic predisposition of nicotine dependence influence COPD risk and lung function; and (2) the genetic pleiotropy follow causal or independent model. We found the genetic predisposition of nicotine dependence was associated with COPD risk, even after adjusting for smoking behavior, indicating genetic pleiotropy and independent model. Two known nicotine dependent loci (15q25.1 and 19q13.2) were associated with smoking adjusted lung function, and 15q25.1 reached genome-wide significance. At various suggestive p-value thresholds, the smoking adjusted lung function traits share association signals with cigarettes per day and former smoking, substantially greater than random chance. Empirical data showed the genetic pleiotropy between nicotine dependence and COPD or lung function. The basis of pleiotropic effect is rather complex, attributable to a large number of genetic variants, and many variants functions through independent model, where the pleiotropic variants directly affect lung function, not mediated by influencing subjects' smoking behavior.

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