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  • Thorgeirsson, T. E. (author)

A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-03-08
  • Springer Science and Business Media LLC,2016

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/236906
  • https://gup.ub.gu.se/publication/236906URI
  • https://doi.org/10.1038/mp.2016.13DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-120800URI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Steinberg, S. (author)
  • Reginsson, G. W. (author)
  • Bjornsdottir, G. (author)
  • Rafnar, T. (author)
  • Jonsdottir, I. (author)
  • Helgadottir, A. (author)
  • Gretarsdottir, S. (author)
  • Helgadottir, H. (author)
  • Jonsson, S. (author)
  • Matthiasson, S. E. (author)
  • Gislason, T. (author)
  • Tyrfingsson, T. (author)
  • Gudbjartsson, T. (author)
  • Isaksson, H. J. (author)
  • Hardardottir, H. (author)
  • Sigvaldason, A. (author)
  • Kiemeney, L. A. (author)
  • Haugen, A. (author)
  • Zienolddiny, S. (author)
  • Wolf, H. J. (author)
  • Franklin, W. A. (author)
  • Panadero, A. (author)
  • Mayordomo, J. I. (author)
  • Hall, I. P. (author)
  • Rönmark, EvaUmeå universitet,Yrkes- och miljömedicin,The OLIN studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Luleå, Sweden(Swepub:umu)evra0004 (author)
  • Lundbäck, Bo,1948Gothenburg University,Göteborgs universitet,Krefting Research Centre(Swepub:gu)xlunbo (author)
  • Dirksen, A. (author)
  • Ashraf, H. (author)
  • Pedersen, J. H. (author)
  • Masson, G. (author)
  • Sulem, P. (author)
  • Thorsteinsdottir, U. (author)
  • Gudbjartsson, D. F. (author)
  • Stefansson, K. (author)
  • Umeå universitetYrkes- och miljömedicin (creator_code:org_t)

Related titles

  • In:Molecular Psychiatry: Springer Science and Business Media LLC21:5, s. 594-6001359-41841476-5578

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