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  • Dand, NickKings Coll London, England (author)

Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-08-24
  • OXFORD UNIV PRESS,2017
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-142974
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-142974URI
  • https://doi.org/10.1093/hmg/ddx328DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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

Notes

  • Funding Agencies|Medical Research Council (MRC) Stratified Medicine award [MR/L011808/1]; Psoriasis Association [RG2/10]; MRC Clinical Training Fellowship [MR/L001543/1]; NIHR Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust; Kings College London; NIHR Biomedical Research Centre at South London; Maudsley NHS Foundation Trust; Maudsley Charity [980]; Guys and St Thomass Charity [STR130505]; MRC grant [G0000934]; Wellcome Trust grant [068545/Z/02]; German Federal Ministry of Education and Research (BMBF) [01ZX1306A]; PopGen Biobank (Kiel, Germany) [01EY1103]; Helmholtz Zentrum Munchen - German Research Center for Environmental Health; BMBF; State of Bavaria; Munich Center of Health Sciences (MC Health); Ludwig-Maximilians-Universitat, of LMUinnovativ; BMBF [01ZZ9603, 01ZZ0103, 01ZZ0403, 03152061A, 03Z1CN22]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg -West Pomerania; network Greifswald Approach to Individualized Medicine (GANI MED); Federal State of Mecklenburg West Pomerania; BMBF Metarthros grant [01EC1407A]; National Institutes of Health [R01AR042742, R01AR050511, R01AR054966, R01AR063611, R01AR065183]; GAIN award from the Foundation for the National Institutes of Health; Ann Arbor Veterans Affairs Hospital; Taubman Medical Research Institute; International Psoriasis Council
  • Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

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  • Mucha, SoerenChristian Albrechts University of Kiel, Germany (author)
  • Tsoi, Lam C.University of Michigan, MI 48109 USA (author)
  • Mahil, Satveer K.Kings Coll London, England (author)
  • Stuart, Philip E.University of Michigan, MI USA (author)
  • Arnold, AndreasUniversity of Medical Greifswald, Germany (author)
  • Baurecht, HansjoergUniversity Hospital Schleswigholstein, Germany (author)
  • David Burden, A.University of Glasgow, Scotland (author)
  • Callis Duffin, KristinaUniversity of Utah, UT USA (author)
  • Chandran, VinodUniversity of Toronto, Canada; University of Health Network, Canada (author)
  • Curtis, Charles J.NIHR, England; Maudsley NHS Fdn Trust, England; Kings Coll London, England; Kings Coll London, England (author)
  • Das, SayantanUniversity of Michigan, MI 48109 USA (author)
  • Ellinghaus, DavidChristian Albrechts University of Kiel, Germany (author)
  • Ellinghaus, EvaChristian Albrechts University of Kiel, Germany (author)
  • Enerbäck, CharlottaLinköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland(Swepub:liu)chaen00 (author)
  • Esko, TonuUniversity of Tartu, Estonia (author)
  • Gladman, Dafna D.University of Toronto, Canada; University of Health Network, Canada (author)
  • Griffiths, Christopher E. M.University of Manchester, England (author)
  • Gudjonsson, Johann E.University of Michigan, MI USA (author)
  • Hoffman, PerUniversity of Basel, Switzerland; University of Bonn, Germany (author)
  • Homuth, GeorgUniversity of Med, Germany; Ernst Moritz Arndt University of Greifswald, Germany (author)
  • Hueffmeier, UlrikeUniversity Hospital Schleswigholstein, Germany; Friedrich Alexander University of Erlangen Nurnberg, Germany (author)
  • Krueger, Gerald G.University of Utah, UT USA (author)
  • Laudes, MatthiasChristian Albrechts University of Kiel, Germany (author)
  • Hyuck Lee, SangNIHR, England; Maudsley NHS Fdn Trust, England; Kings Coll London, England; Kings Coll London, England (author)
  • Lieb, WolfgangChristian Albrechts University of Kiel, Germany (author)
  • Lim, Henry W.Henry Ford Hospital, MI 48202 USA (author)
  • Loehr, SabineFriedrich Alexander University of Erlangen Nurnberg, Germany (author)
  • Mrowietz, UlrichDepartment of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany (author)
  • Mueller-Nurayid, MartinaHelmholtz Zentrum Munich, Germany (author)
  • Noethen, MarkusUniversity of Bonn, Germany (author)
  • Peters, AnnetteHelmholtz Zentrum Munich, Germany (author)
  • Rahman, ProtonMem University of Newfoundland, Canada (author)
  • Reis, AndreFriedrich Alexander University of Erlangen Nurnberg, Germany (author)
  • Reynolds, Nick J.Newcastle University, England; Newcastle Hospital NHS Fdn Trust, England (author)
  • Rodriguez, ElkeUniversity Hospital Schleswigholstein, Germany (author)
  • Schmidt, Carsten O.University of Medical Greifswald, Germany (author)
  • Spain, Sarah L.Kings Coll London, England (author)
  • Strauch, KonstantinHelmholtz Zentrum Munich, Germany (author)
  • Tejasvi, TrilokrajUniversity of Michigan, MI USA (author)
  • Voorhees, John J.University of Michigan, MI USA (author)
  • Warren, Richard B.University of Manchester, England (author)
  • Weichenthal, MichaelUniversity of Medical Centre Schleswig Holstein, Germany (author)
  • Weidinger, StephanUniversity Hospital Schleswigholstein, Germany (author)
  • Zawistowski, MatthewUniversity of Michigan, MI 48109 USA (author)
  • Nair, Rajan P.University of Michigan, MI USA (author)
  • Capon, FrancescaKings Coll London, England (author)
  • Smith, Catherine H.Kings Coll London, England (author)
  • Trembath, Richard C.Kings Coll London, England (author)
  • Abecasis, Goncalo R.University of Michigan, MI 48109 USA (author)
  • Elder, James T.University of Michigan, MI USA; Ann Arbor Vet Hospital, MI USA (author)
  • Franke, AndreChristian Albrechts University of Kiel, Germany (author)
  • Simpson, Michael A.Kings Coll London, England (author)
  • Barker, Jonathan N.Kings Coll London, England (author)
  • Kings Coll London, EnglandChristian Albrechts University of Kiel, Germany (creator_code:org_t)

Related titles

  • In:Human Molecular Genetics: OXFORD UNIV PRESS26:21, s. 4301-43130964-69061460-2083

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