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Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population
Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a w...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509597/ https://www.ncbi.nlm.nih.gov/pubmed/33033484 http://dx.doi.org/10.3389/fpsyt.2020.564239 |
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author | Li, Meng Chen, Ying Yao, Jianhua Lu, Sheming Guan, Ying Xu, Yuqiong Liu, Qiang Sun, Silong Mi, Qili Mei, Junpu Li, Xuemei Miao, Mingming Zhao, Shancen Zhu, Zhouhai |
author_facet | Li, Meng Chen, Ying Yao, Jianhua Lu, Sheming Guan, Ying Xu, Yuqiong Liu, Qiang Sun, Silong Mi, Qili Mei, Junpu Li, Xuemei Miao, Mingming Zhao, Shancen Zhu, Zhouhai |
author_sort | Li, Meng |
collection | PubMed |
description | Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. Thirteen single-nucleotide polymorphisms (SNPs) of the raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P < 5 x 10(−8)) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and sushi multiple domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1,329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5/ANKRD30A, two genes involved in cancer development, were identified and replicated. Within RFTN1, two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T, and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in the CSMD1 gene showing a significant association with smoking initiation. Further bioinformatics functional assessment suggested that RFTN1 may participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population. |
format | Online Article Text |
id | pubmed-7509597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75095972020-10-07 Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population Li, Meng Chen, Ying Yao, Jianhua Lu, Sheming Guan, Ying Xu, Yuqiong Liu, Qiang Sun, Silong Mi, Qili Mei, Junpu Li, Xuemei Miao, Mingming Zhao, Shancen Zhu, Zhouhai Front Psychiatry Psychiatry Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. Thirteen single-nucleotide polymorphisms (SNPs) of the raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P < 5 x 10(−8)) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and sushi multiple domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1,329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5/ANKRD30A, two genes involved in cancer development, were identified and replicated. Within RFTN1, two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T, and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in the CSMD1 gene showing a significant association with smoking initiation. Further bioinformatics functional assessment suggested that RFTN1 may participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population. Frontiers Media S.A. 2020-09-09 /pmc/articles/PMC7509597/ /pubmed/33033484 http://dx.doi.org/10.3389/fpsyt.2020.564239 Text en Copyright © 2020 Li, Chen, Yao, Lu, Guan, Xu, Liu, Sun, Mi, Mei, Li, Miao, Zhao and Zhu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Li, Meng Chen, Ying Yao, Jianhua Lu, Sheming Guan, Ying Xu, Yuqiong Liu, Qiang Sun, Silong Mi, Qili Mei, Junpu Li, Xuemei Miao, Mingming Zhao, Shancen Zhu, Zhouhai Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population |
title | Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population |
title_full | Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population |
title_fullStr | Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population |
title_full_unstemmed | Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population |
title_short | Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population |
title_sort | genome-wide association study of smoking behavior traits in a chinese han population |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509597/ https://www.ncbi.nlm.nih.gov/pubmed/33033484 http://dx.doi.org/10.3389/fpsyt.2020.564239 |
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