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van Zuydam, N.R.* ; Stiby, A.* ; Abdalla, M.* ; Austin, E.* ; Dahlström, E.H.* ; McLachlan, S.* ; Vlachopoulou, E.* ; Ahlqvist, E.* ; Di Liao, C.* ; Sandholm, N.* ; Forsblom, C.* ; Mahajan, A.* ; Robertson, N.R.* ; Rayner, N.W.* ; Lindholm, E.* ; Sinisalo, J.* ; Perola, M.* ; Kallio, M.* ; Weiss, E.* ; Price, J.* ; Paterson, A.* ; Klein, B.* ; Salomaa, V.* ; Palmer, C.N.A.* ; Groop, P.H.* ; Groop, L.* ; McCarthy, M.I.* ; de Andrade, M.* ; Morris, A.P.* ; Hopewell, J.C.* ; Colhoun, H.M.* ; Kullo, I.J.* ; SUMMIT consortium (Thorand, B.)

Genome-wide association study of peripheral artery disease.

Circ. Genom. Precis. Med. 14:e002862 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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 (Passociation ≤5×10-8) associations with PAD in 449 548 (Ncases=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], Pdiabetes=2.5×10-9, Pinteractionwithdiabetes=5.3×10-7). Furthermore, in smokers, rs12910984 at the CHRNA3 locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11-1.19], Psmokers=9.3×10-10, Pinteractionwithsmoking=3.9×10-5). 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Diabetes ; Genome-wide Association Study ; Peripheral Vascular Disease ; Smoking
ISSN (print) / ISBN 2574-8300
e-ISSN 2574-8300
Zeitschrift Circulation Genomic and precision medicine
Quellenangaben Band: 14, Heft: 5, Seiten: , Artikelnummer: e002862 Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Philadelphia, Pa.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Förderungen Medical Research Council
NIDDK NIH HHS
Chief Scientist Office [UK]
British Heart Foundation