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Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence

While substantial progress has been made in finding genetic variants associated with nicotine dependence (ND), a large proportion of the genetic variants remain undiscovered. The current research focuses have shifted toward uncovering rare variants, gene-gene/gene-environment interactions, and struc...

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Autores principales: Zhang, Xuefen, Lan, Tongtong, Wang, Tong, Xue, Wei, Tong, Xiaoran, Ma, Tengfei, Liu, Guifen, Lu, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534062/
https://www.ncbi.nlm.nih.gov/pubmed/31164900
http://dx.doi.org/10.3389/fgene.2019.00448
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author Zhang, Xuefen
Lan, Tongtong
Wang, Tong
Xue, Wei
Tong, Xiaoran
Ma, Tengfei
Liu, Guifen
Lu, Qing
author_facet Zhang, Xuefen
Lan, Tongtong
Wang, Tong
Xue, Wei
Tong, Xiaoran
Ma, Tengfei
Liu, Guifen
Lu, Qing
author_sort Zhang, Xuefen
collection PubMed
description While substantial progress has been made in finding genetic variants associated with nicotine dependence (ND), a large proportion of the genetic variants remain undiscovered. The current research focuses have shifted toward uncovering rare variants, gene-gene/gene-environment interactions, and structural variations predisposing to ND, the impact of genetic heterogeneity in ND has been nevertheless paid less attention. The study of genetic heterogeneity in ND not only could enhance the power of detecting genetic variants with heterogeneous effects in the population but also improve our understanding of genetic etiology of ND. As an initial step to understand genetic heterogeneity in ND, we applied a newly developed heterogeneity weighted U (HWU) method to 26 ND-related genes, investigating heterogeneous effects of these 26 genes in ND. We found no strong evidence of genetic heterogeneity in genes such as CHRNA5. However, results from our analysis suggest heterogeneous effects of CHRNA6 and CHRNB3 on nicotine dependence in males and females. Following the gene-based analysis, we further conduct a joint association analysis of two gene clusters, CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6. While both CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6 clusters are significantly associated with ND, there is a much stronger association of CHRNB3-CHRNA6 with ND when considering heterogeneous effects in gender (p-value = 2.11E-07).
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spelling pubmed-65340622019-06-04 Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence Zhang, Xuefen Lan, Tongtong Wang, Tong Xue, Wei Tong, Xiaoran Ma, Tengfei Liu, Guifen Lu, Qing Front Genet Genetics While substantial progress has been made in finding genetic variants associated with nicotine dependence (ND), a large proportion of the genetic variants remain undiscovered. The current research focuses have shifted toward uncovering rare variants, gene-gene/gene-environment interactions, and structural variations predisposing to ND, the impact of genetic heterogeneity in ND has been nevertheless paid less attention. The study of genetic heterogeneity in ND not only could enhance the power of detecting genetic variants with heterogeneous effects in the population but also improve our understanding of genetic etiology of ND. As an initial step to understand genetic heterogeneity in ND, we applied a newly developed heterogeneity weighted U (HWU) method to 26 ND-related genes, investigating heterogeneous effects of these 26 genes in ND. We found no strong evidence of genetic heterogeneity in genes such as CHRNA5. However, results from our analysis suggest heterogeneous effects of CHRNA6 and CHRNB3 on nicotine dependence in males and females. Following the gene-based analysis, we further conduct a joint association analysis of two gene clusters, CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6. While both CHRNA5-CHRNA3-CHRNB4 and CHRNB3-CHRNA6 clusters are significantly associated with ND, there is a much stronger association of CHRNB3-CHRNA6 with ND when considering heterogeneous effects in gender (p-value = 2.11E-07). Frontiers Media S.A. 2019-05-17 /pmc/articles/PMC6534062/ /pubmed/31164900 http://dx.doi.org/10.3389/fgene.2019.00448 Text en Copyright © 2019 Zhang, Lan, Wang, Xue, Tong, Ma, Liu and Lu. 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 Genetics
Zhang, Xuefen
Lan, Tongtong
Wang, Tong
Xue, Wei
Tong, Xiaoran
Ma, Tengfei
Liu, Guifen
Lu, Qing
Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence
title Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence
title_full Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence
title_fullStr Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence
title_full_unstemmed Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence
title_short Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence
title_sort considering genetic heterogeneity in the association analysis finds genes associated with nicotine dependence
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534062/
https://www.ncbi.nlm.nih.gov/pubmed/31164900
http://dx.doi.org/10.3389/fgene.2019.00448
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