Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.

Heterogeneous phenotypes of complex disorders pose a great challenge for genetic association studies and for the development of personalized treatment strategies. Cluster analysis of phenotypic data has been recently proposed as a reliable auxiliary method for such studies. A cohort of 236 treatment...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Judit Lazary, Peter Dome, Iren Csala, Gabor Kovacs, Gabor Faludi, Mari Kaunisto, Balazs Dome
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a9712a0c2274ed0a52338071f2fdce8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4a9712a0c2274ed0a52338071f2fdce8
record_format	dspace
spelling	oai:doaj.org-article:4a9712a0c2274ed0a52338071f2fdce82021-11-18T08:34:50ZMassive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.1932-620310.1371/journal.pone.0087141https://doaj.org/article/4a9712a0c2274ed0a52338071f2fdce82014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24498031/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Heterogeneous phenotypes of complex disorders pose a great challenge for genetic association studies and for the development of personalized treatment strategies. Cluster analysis of phenotypic data has been recently proposed as a reliable auxiliary method for such studies. A cohort of 236 treatment-seeking smokers was investigated after overnight nicotine abstinence. Alpha4 nicotinic acetylcholine receptor (nAChR) subunit-related phenotypes were assessed by the Fagerström Test for Nicotine Dependence (FTND), exhaled carbon monoxide (CO) measurements, the Minnesota Nicotine Withdrawal Scale (MNWS) and the Zung Self-Rating Depression Scale (ZSDS). Seven tag SNPs (single-nucleotide polymorphisms) across CHRNA4 (the gene encoding alpha4 subunit of the nicotinic acetylcholine receptor) were genotyped and two-step cluster analysis was used for phenotypic cluster characterization. Haplotype estimation was determined by HapStat module of R 2.0 software. Three different phenotypic clusters were identified and the C3 cluster was characterized by the highest ZSDS and MNWS scores compared to others. Furthermore, lifetime prevalence of major depression was significantly higher in the C3 cluster (p = 0.019). In genetic association tests, this cluster was also significantly associated with rs3787138 genotypes (p = 0.004) while haplotype analyses of three SNPs (rs3787138, rs1044396, rs3787140) revealed that the risk for C3 phenotype was almost three times higher in GCC haplotype carriers compared to others (pperm = 0.013). This is the first report on a significant association between CHRNA4 variants and a subgroup of smokers characterized by massive withdrawal symptoms and affective vulnerability. Identification of such a phenotypic cluster can be a pivotal step for further pharmacogenetic studies on ligands of the alpha4 nAChR subunit. Our results suggest that performing cluster analysis in genetic association studies can be proposed for complex disorders.Judit LazaryPeter DomeIren CsalaGabor KovacsGabor FaludiMari KaunistoBalazs DomePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e87141 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Judit Lazary Peter Dome Iren Csala Gabor Kovacs Gabor Faludi Mari Kaunisto Balazs Dome Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
description	Heterogeneous phenotypes of complex disorders pose a great challenge for genetic association studies and for the development of personalized treatment strategies. Cluster analysis of phenotypic data has been recently proposed as a reliable auxiliary method for such studies. A cohort of 236 treatment-seeking smokers was investigated after overnight nicotine abstinence. Alpha4 nicotinic acetylcholine receptor (nAChR) subunit-related phenotypes were assessed by the Fagerström Test for Nicotine Dependence (FTND), exhaled carbon monoxide (CO) measurements, the Minnesota Nicotine Withdrawal Scale (MNWS) and the Zung Self-Rating Depression Scale (ZSDS). Seven tag SNPs (single-nucleotide polymorphisms) across CHRNA4 (the gene encoding alpha4 subunit of the nicotinic acetylcholine receptor) were genotyped and two-step cluster analysis was used for phenotypic cluster characterization. Haplotype estimation was determined by HapStat module of R 2.0 software. Three different phenotypic clusters were identified and the C3 cluster was characterized by the highest ZSDS and MNWS scores compared to others. Furthermore, lifetime prevalence of major depression was significantly higher in the C3 cluster (p = 0.019). In genetic association tests, this cluster was also significantly associated with rs3787138 genotypes (p = 0.004) while haplotype analyses of three SNPs (rs3787138, rs1044396, rs3787140) revealed that the risk for C3 phenotype was almost three times higher in GCC haplotype carriers compared to others (pperm = 0.013). This is the first report on a significant association between CHRNA4 variants and a subgroup of smokers characterized by massive withdrawal symptoms and affective vulnerability. Identification of such a phenotypic cluster can be a pivotal step for further pharmacogenetic studies on ligands of the alpha4 nAChR subunit. Our results suggest that performing cluster analysis in genetic association studies can be proposed for complex disorders.
format	article
author	Judit Lazary Peter Dome Iren Csala Gabor Kovacs Gabor Faludi Mari Kaunisto Balazs Dome
author_facet	Judit Lazary Peter Dome Iren Csala Gabor Kovacs Gabor Faludi Mari Kaunisto Balazs Dome
author_sort	Judit Lazary
title	Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
title_short	Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
title_full	Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
title_fullStr	Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
title_full_unstemmed	Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
title_sort	massive withdrawal symptoms and affective vulnerability are associated with variants of the chrna4 gene in a subgroup of smokers.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4a9712a0c2274ed0a52338071f2fdce8
work_keys_str_mv	AT juditlazary massivewithdrawalsymptomsandaffectivevulnerabilityareassociatedwithvariantsofthechrna4geneinasubgroupofsmokers AT peterdome massivewithdrawalsymptomsandaffectivevulnerabilityareassociatedwithvariantsofthechrna4geneinasubgroupofsmokers AT irencsala massivewithdrawalsymptomsandaffectivevulnerabilityareassociatedwithvariantsofthechrna4geneinasubgroupofsmokers AT gaborkovacs massivewithdrawalsymptomsandaffectivevulnerabilityareassociatedwithvariantsofthechrna4geneinasubgroupofsmokers AT gaborfaludi massivewithdrawalsymptomsandaffectivevulnerabilityareassociatedwithvariantsofthechrna4geneinasubgroupofsmokers AT marikaunisto massivewithdrawalsymptomsandaffectivevulnerabilityareassociatedwithvariantsofthechrna4geneinasubgroupofsmokers AT balazsdome massivewithdrawalsymptomsandaffectivevulnerabilityareassociatedwithvariantsofthechrna4geneinasubgroupofsmokers
_version_	1718421619483869184

Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.

Ejemplares similares