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  • Nielsen, Jonas B.Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. (författare)

Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development

  • Artikel/kapitelEngelska2018

Förlag, utgivningsår, omfång ...

  • Elsevier BV,2018
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-341499
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-341499URI
  • https://doi.org/10.1016/j.ajhg.2017.12.003DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Fritsche, Lars G.Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway. (författare)
  • Zhou, WeiUniv Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. (författare)
  • Teslovich, Tanya M.Regeneron Genet Ctr, Tarrytown, NY 10591 USA. (författare)
  • Holmen, Oddgeir L.Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;St Olavs Univ Hosp, Dept Cardiol, N-7030 Trondheim, Norway. (författare)
  • Gustafsson, StefanUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:uu)stegu732 (författare)
  • Gabrielsen, Maiken E.Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway. (författare)
  • Schmidt, Ellen M.Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. (författare)
  • Beaumont, RobinRoyal Devon & Exeter NHS Fdn Trust, Exeter EX2 5WD, Devon, England.;Univ Exeter, Exeter EX2 5WD, Devon, England. (författare)
  • Wolford, Brooke N.Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. (författare)
  • Lin, MaoxuanUniv Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. (författare)
  • Brummett, Chad M.Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. (författare)
  • Preuss, Michael H.Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. (författare)
  • Refsgaard, LenaUniv Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark. (författare)
  • Bottinger, Erwin P.Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY 10029 USA. (författare)
  • Graham, Sarah E.Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA. (författare)
  • Surakka, IdaUniv Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA. (författare)
  • Chu, YunhanNorwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway. (författare)
  • Skogholt, Anne HeidiNorwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway. (författare)
  • Dalen, HavardSt Olavs Univ Hosp, Dept Cardiol, N-7030 Trondheim, Norway.;Nord Trondelag Hosp Trust, Levanger Hosp, Dept Med, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, N-7491 Trondheim, Norway. (författare)
  • Boyle, Alan P.Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. (författare)
  • Oral, HakanUniv Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA. (författare)
  • Herron, Todd J.Univ Michigan, Ctr Arrhythmia Res, Dept Internal Med, Ann Arbor, MI 48109 USA. (författare)
  • Kitzman, JacobUniv Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. (författare)
  • Jalife, JoseUniv Michigan, Ctr Arrhythmia Res, Dept Internal Med, Ann Arbor, MI 48109 USA.;Fdn Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain. (författare)
  • Svendsen, Jesper H.Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark. (författare)
  • Olesen, Morten S.Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Dept Biomed, DK-2200 Copenhagen, Denmark. (författare)
  • Njolstad, IngerUiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway. (författare)
  • Lochen, Maja-LisaUiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway. (författare)
  • Baras, ArisRegeneron Genet Ctr, Tarrytown, NY 10591 USA. (författare)
  • Gottesman, OmriRegeneron Genet Ctr, Tarrytown, NY 10591 USA. (författare)
  • Marcketta, AnthonyRegeneron Genet Ctr, Tarrytown, NY 10591 USA. (författare)
  • O'Dushlaine, ColmRegeneron Genet Ctr, Tarrytown, NY 10591 USA. (författare)
  • Ritchie, Marylyn D.Geisinger Hlth Syst, Danville, PA 17822 USA. (författare)
  • Wilsgaard, TomUiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway. (författare)
  • Loos, Ruth J. F.Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. (författare)
  • Frayling, Timothy M.Royal Devon & Exeter NHS Fdn Trust, Exeter EX2 5WD, Devon, England.;Univ Exeter, Exeter EX2 5WD, Devon, England. (författare)
  • Boehnke, MichaelUniv Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway. (författare)
  • Ingelsson, Erik,1975-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi,Division of Cardiovascular Medicine, Depart- ment of Medicine, Stanford University School of Medicine, Stanford, USA(Swepub:uu)ering425 (författare)
  • Carey, David J. (författare)
  • Dewey, Frederick E.Regeneron Genet Ctr, Tarrytown, NY 10591 USA. (författare)
  • Kang, Hyun M.Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. (författare)
  • Abecasis, Goncalo R.Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway. (författare)
  • Hveem, KristianNorwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;Nord Trondelag Hosp Trust, Levanger Hosp, Dept Med, N-7600 Levanger, Norway. (författare)
  • Willer, Cristen J.Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. (författare)
  • Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:American Journal of Human Genetics: Elsevier BV102:1, s. 103-1150002-92971537-6605

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