Genome-Wide Association Study of Peripheral Artery Disease

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Genome-Wide Association Study of Peripheral Artery Disease

van Zuydam, Natalie (författare): Uppsala 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

Stiby, Alexander (författare): Univ Oxford, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Epidemiol Studies Unit, Oxford, England.,University of Oxford

Abdalla, Moustafa (författare): 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

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Austin, Erin (författare): 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

Dahlstrom, Emma H. (författare): 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

McLachlan, Stela (författare): Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.,University of Edinburgh

Vlachopoulou, Efthymia (författare): Univ Helsinki, Dept Med, Helsinki Univ Cent Hosp, Helsinki, Finland.,University of Helsinki

Ahlqvist, Emma (författare): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Di Liao, Chen (författare): Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.;SickKids, Genet & Genome Biol, Toronto, ON, Canada.,University of Toronto

Sandholm, Niina (författare): 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.,Helsinki University Central Hospital,Folkhälsan Research Center,University of Helsinki

Forsblom, Carol (författare): 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

Mahajan, Anubha (författare): Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Genentech Inc, San Francisco, CA USA.,University of Oxford

Robertson, Neil R. (författare): 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

Rayner, N. William (författare): Univ 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

Lindholm, Eero (författare): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Sinisalo, Juha (författare): Univ Helsinki, Heart & Lung Ctr, Helsinki, Finland.,University of Helsinki

Perola, Markus (författare): Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Finnish Inst Hlth & Welf, Helsinki, Finland.,University of Helsinki

Kallio, Milla (författare): Univ Helsinki, Vasc Surg, Abdominal Ctr, Helsinki, Finland.,University of Helsinki

Weiss, Emily (författare): Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.,University of Edinburgh

Price, Jackie (författare): Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.,University of Edinburgh

Paterson, Andrew (författare): Univ 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

Klein, Barbara (författare): Univ Wisconsin Madison, Ocular Epidemiol Res Grp, Madison, WI USA.,University of Wisconsin-Madison

Salomaa, Veikko (författare): Finnish Inst Hlth & Welf, Helsinki, Finland.

Palmer, Colin N. A. (författare): Univ Dundee, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Ninewells Hosp & Med Sch, Dundee, Scotland.,University of Dundee

Groop, Per-Henrik (författare): 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.;Monash Univ, Dept Med, Cent Clin Sch, Melbourne, Vic, Australia.,Helsinki University Central Hospital,University of Helsinki,Folkhälsan Research Center

Groop, Leif (författare): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Helsinki

McCarthy, Mark I. (författare): 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

de Andrade, Mariza (författare): 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

Morris, Andrew P. (författare): 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.

Hopewell, Jemma C. (författare): Univ Oxford, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Epidemiol Studies Unit, Oxford, England.,University of Oxford

Colhoun, Helen M. (författare): Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp Campus, Edinburgh, Midlothian, Scotland.,University of Edinburgh

Kullo, Iftikhar J. (författare): 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

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(creator_code:org_t)

Lippincott Williams & Wilkins, 2021
2021
Engelska.
Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 2574-8300. ; 14:5

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://uu.diva-port... (primary) (Raw object); http://dx.doi.org/10... (free); https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

diabetes
genome-wide association study
peripheral vascular disease
smoking
diabetes
genome-wide association study
peripheral vascular disease
smoking

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Av lärosätet: Uppsala universitet; Lunds universitet

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