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  • van Zuydam, NatalieUppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.,University of Oxford (author)

Genome-Wide Association Study of Peripheral Artery Disease

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • Lippincott Williams & Wilkins,2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-458405
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-458405URI
  • https://doi.org/10.1161/CIRCGEN.119.002862DOI
  • https://lup.lub.lu.se/record/e1caed53-8988-4aec-bc62-cd3abd2a9d95URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

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

Notes

  • Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status. Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status. Results: We identified 5 genome-wide significant (P-association <= 5x10(-8)) associations with PAD in 449 548 (N-cases=12 086) individuals of European ancestry near LPA (lipoprotein [a]), CDKN2BAS1 (CDKN2B antisense RNA 1), SH2B3 (SH2B adaptor protein 3) - PTPN11 (protein tyrosine phosphatase non-receptor type 11), HDAC9 (histone deacetylase 9), and CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit) loci (which overlapped previously reported associations). Meta-analysis with variants previously associated with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the CCSER1 (coiled-coil serine rich protein 1) locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32-1.74], P-diabetes=2.5x10(-9), P-interactionwithdiabetes=5.3x10(-7)). Furthermore, in smokers, rs12910984 at the CHRNA3 locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11-1.19], P-smokers=9.3x10(-10), P-interactionwithsmoking=3.9x10(-5)). Conclusions: Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.

Subject headings and genre

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  • Stiby, AlexanderUniv Oxford, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Epidemiol Studies Unit, Oxford, England.,University of Oxford (author)
  • Abdalla, MoustafaUniv Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.,University of Oxford (author)
  • Austin, ErinMayo Clin, Dept Cardiovasc Med, 200 First St SW, Rochester, MN 55905 USA.;Mayo Clin, Gonda Vasc Ctr, 200 First St SW, Rochester, MN 55905 USA.,Mayo Clinic Minnesota (author)
  • Dahlstrom, Emma H.Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr, Nephrol, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Res Program Clin & Mol Metab, Fac Med, Helsinki, Finland.,Folkhälsan Research Center,University of Helsinki,Helsinki University Central Hospital (author)
  • McLachlan, StelaUniv Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.,University of Edinburgh (author)
  • Vlachopoulou, EfthymiaUniv Helsinki, Dept Med, Helsinki Univ Cent Hosp, Helsinki, Finland.,University of Helsinki (author)
  • Ahlqvist, EmmaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)infl-eah (author)
  • Di Liao, ChenUniv Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.;SickKids, Genet & Genome Biol, Toronto, ON, Canada.,University of Toronto (author)
  • Sandholm, NiinaFolkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr, Nephrol, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Res Program Clin & Mol Metab, Fac Med, Helsinki, Finland.,Helsinki University Central Hospital,Folkhälsan Research Center,University of Helsinki (author)
  • Forsblom, CarolFolkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr, Nephrol, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Res Program Clin & Mol Metab, Fac Med, Helsinki, Finland.,Folkhälsan Research Center,University of Helsinki,Helsinki University Central Hospital (author)
  • Mahajan, AnubhaUniv Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Genentech Inc, San Francisco, CA USA.,University of Oxford (author)
  • Robertson, Neil R.Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.,University of Oxford (author)
  • Rayner, N. WilliamUniv Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.,University of Oxford (author)
  • Lindholm, EeroLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-eli (author)
  • Sinisalo, JuhaUniv Helsinki, Heart & Lung Ctr, Helsinki, Finland.,University of Helsinki (author)
  • Perola, MarkusUniv Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Finnish Inst Hlth & Welf, Helsinki, Finland.,University of Helsinki(Swepub:lu)med-mkp (author)
  • Kallio, MillaUniv Helsinki, Vasc Surg, Abdominal Ctr, Helsinki, Finland.,University of Helsinki (author)
  • Weiss, EmilyUniv Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.,University of Edinburgh (author)
  • Price, JackieUniv Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.,University of Edinburgh (author)
  • Paterson, AndrewUniv Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.;SickKids, Genet & Genome Biol, Toronto, ON, Canada.,University of Toronto,University of Manchester,University of Liverpool (author)
  • Klein, BarbaraUniv Wisconsin Madison, Ocular Epidemiol Res Grp, Madison, WI USA.,University of Wisconsin-Madison (author)
  • Salomaa, VeikkoFinnish Inst Hlth & Welf, Helsinki, Finland. (author)
  • Palmer, Colin N. A.Univ Dundee, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Ninewells Hosp & Med Sch, Dundee, Scotland.,University of Dundee (author)
  • Groop, Per-HenrikFolkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr, Nephrol, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Res Program Clin & Mol Metab, Fac Med, Helsinki, Finland.;Monash Univ, Dept Med, Cent Clin Sch, Melbourne, Vic, Australia.,Helsinki University Central Hospital,University of Helsinki,Folkhälsan Research Center (author)
  • Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Helsinki(Swepub:lu)endo-lgr (author)
  • McCarthy, Mark I.Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.;Genentech Inc, San Francisco, CA USA.,University of Oxford,Oxford University Hospitals NHS Foundation Trust (author)
  • de Andrade, MarizaMayo Clin, Dept Cardiovasc Med, 200 First St SW, Rochester, MN 55905 USA.;Mayo Clin, Gonda Vasc Ctr, 200 First St SW, Rochester, MN 55905 USA.,Mayo Clinic Minnesota (author)
  • Morris, Andrew P.Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Manchester, Ctr Genet & Genom Versus Arthrit, Ctr Musculoskeletal Res, Manchester, Lancs, England. (author)
  • Hopewell, Jemma C.Univ Oxford, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Epidemiol Studies Unit, Oxford, England.,University of Oxford (author)
  • Colhoun, Helen M.Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp Campus, Edinburgh, Midlothian, Scotland.,University of Edinburgh (author)
  • Kullo, Iftikhar J.Mayo Clin, Dept Cardiovasc Med, 200 First St SW, Rochester, MN 55905 USA.;Mayo Clin, Gonda Vasc Ctr, 200 First St SW, Rochester, MN 55905 USA.,Mayo Clinic Minnesota (author)
  • Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

Related titles

  • In:Circulation: Lippincott Williams & Wilkins14:52574-8300

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