Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Genome-Wide Association Study of Peripheral Artery Disease

van Zuydam, Natalie R. ; Stiby, Alexander ; Abdalla, Moustafa ; Austin, Erin ; Dahlström, Emma H. ; McLachlan, Stela ; Vlachopoulou, Efthymia ; Ahlqvist, Emma LU ; Di Liao, Chen and Sandholm, Niina , et al. (2021) In Circulation. Genomic and precision medicine 14(5). p.002862-002862
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
diabetes, genome-wide association study, peripheral vascular disease, smoking
in
Circulation. Genomic and precision medicine
volume
14
issue
5
pages
002862 - 002862
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85119458238
  • pmid:34601942
ISSN
2574-8300
DOI
10.1161/CIRCGEN.119.002862
language
English
LU publication?
yes
id
e1caed53-8988-4aec-bc62-cd3abd2a9d95
date added to LUP
2021-12-03 11:15:10
date last changed
2024-04-20 18:04:48
@article{e1caed53-8988-4aec-bc62-cd3abd2a9d95,
  abstract     = {{<p>BACKGROUND: Peripheral artery disease (PAD) affects &gt;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.</p>}},
  author       = {{van Zuydam, Natalie R. and Stiby, Alexander and Abdalla, Moustafa and Austin, Erin and Dahlström, Emma H. and McLachlan, Stela and Vlachopoulou, Efthymia and Ahlqvist, Emma and Di Liao, Chen and Sandholm, Niina and Forsblom, Carol and Mahajan, Anubha and Robertson, Neil R. and Rayner, N. William and Lindholm, Eero and Sinisalo, Juha and Perola, Markus and Kallio, Milla and Weiss, Emily and Price, Jackie and Paterson, Andrew and Klein, Barbara and Salomaa, Veikko and Palmer, Colin N.A. and Groop, Per Henrik and Groop, Leif and McCarthy, Mark I. and de Andrade, Mariza and Morris, Andrew P. and Hopewell, Jemma C. and Colhoun, Helen M. and Kullo, Iftikhar J.}},
  issn         = {{2574-8300}},
  keywords     = {{diabetes; genome-wide association study; peripheral vascular disease; smoking}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{002862--002862}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Circulation. Genomic and precision medicine}},
  title        = {{Genome-Wide Association Study of Peripheral Artery Disease}},
  url          = {{http://dx.doi.org/10.1161/CIRCGEN.119.002862}},
  doi          = {{10.1161/CIRCGEN.119.002862}},
  volume       = {{14}},
  year         = {{2021}},
}