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A rare missense mut...
A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences
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Thorgeirsson, T. E. (author)
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Steinberg, S. (author)
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Reginsson, G. W. (author)
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Bjornsdottir, G. (author)
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Rafnar, T. (author)
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Jonsdottir, I. (author)
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Helgadottir, A. (author)
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Gretarsdottir, S. (author)
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Helgadottir, H. (author)
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Jonsson, S. (author)
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Matthiasson, S. E. (author)
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Gislason, T. (author)
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Tyrfingsson, T. (author)
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Gudbjartsson, T. (author)
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Isaksson, H. J. (author)
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Hardardottir, H. (author)
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Sigvaldason, A. (author)
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Kiemeney, L. A. (author)
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Haugen, A. (author)
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Zienolddiny, S. (author)
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Wolf, H. J. (author)
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Franklin, W. A. (author)
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Panadero, A. (author)
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Mayordomo, J. I. (author)
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Hall, I. P. (author)
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- Rönmark, Eva (author)
- Umeå universitet,Yrkes- och miljömedicin,The OLIN studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå, Sweden
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- Lundbäck, Bo, 1948 (author)
- Gothenburg University,Göteborgs universitet,Krefting Research Centre
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Dirksen, A. (author)
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Ashraf, H. (author)
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Pedersen, J. H. (author)
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Masson, G. (author)
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Sulem, P. (author)
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Thorsteinsdottir, U. (author)
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Gudbjartsson, D. F. (author)
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Stefansson, K. (author)
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(creator_code:org_t)
- 2016-03-08
- 2016
- English.
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:5, s. 594-600
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P = 1.2 x 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P = 4.0 x 10(-4)), chronic obstructive pulmonary disease (COPD; P = 9.3 x 10(-4)), peripheral artery disease (PAD; P = 0.090) and abdominal aortic aneurysms (AAAs; P = 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49, P = 2.2 x 10(-4)), COPD (OR = 3.22, P = 2.9 x 10(-4)), PAD (OR = 3.47, P = 9.2 x 10(-3)) and AAA (OR = 6.44, P = 6.3 x 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P = 6.8 x 10(-5)), particularly for early-onset cases (P = 2.1 x 10(-7)). Our results are in agreement with functional studies showing that the human alpha 4 beta 2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- nicotinic acetylcholine-receptors
- genome-wide association
- lung-cancer
- pharmacological chaperone
- susceptibility locus
- sequence variants
- fagerstrom test
- heavy smoking
- dependence
- smokers
- Biochemistry & Molecular Biology
- Neurosciences & Neurology
- Psychiatry
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Thorgeirsson, T. ...
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Steinberg, S.
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Reginsson, G. W.
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Bjornsdottir, G.
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Rafnar, T.
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Jonsdottir, I.
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show more...
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Helgadottir, A.
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Gretarsdottir, S ...
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Helgadottir, H.
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Jonsson, S.
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Matthiasson, S. ...
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Gislason, T.
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Tyrfingsson, T.
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Gudbjartsson, T.
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Isaksson, H. J.
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Hardardottir, H.
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Sigvaldason, A.
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Kiemeney, L. A.
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Haugen, A.
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Zienolddiny, S.
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Wolf, H. J.
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Franklin, W. A.
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Panadero, A.
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Mayordomo, J. I.
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Hall, I. P.
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Rönmark, Eva
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Lundbäck, Bo, 19 ...
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Dirksen, A.
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Ashraf, H.
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Pedersen, J. H.
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Masson, G.
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Sulem, P.
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Thorsteinsdottir ...
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Gudbjartsson, D. ...
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Stefansson, K.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Molecular Psychi ...
- By the university
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University of Gothenburg
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Umeå University