Dataset Information

Genome-Wide Association Study of Peripheral Artery Disease.

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 identified 5 genome-wide significant (P_association ≤5×10^-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=2.5×10^-9, P_{interactionwithdiabetes}=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], P_smokers=9.3×10^-10, P_{interactionwithsmoking}=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.

SUBMITTER: van Zuydam NR

PROVIDER: S-EPMC8542067 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Genome-Wide Association Study of Peripheral Artery Disease.

van Zuydam Natalie R NR Stiby Alexander A Abdalla Moustafa M Austin Erin E Dahlström Emma H EH Dahlström Emma H EH McLachlan Stela S Vlachopoulou Efthymia E Ahlqvist Emma E Di Liao Chen C Sandholm Niina N Forsblom Carol C Mahajan Anubha A Robertson Neil R NR Rayner N William NW Lindholm Eero E Sinisalo Juha J Perola Markus M Kallio Milla M Weiss Emily E Price Jackie J Paterson Andrew A Klein Barbara B Salomaa Veikko V Palmer Colin N A CNA Groop Per-Henrik PH Groop Leif L McCarthy Mark I MI de Andrade Mariza M Morris Andrew P AP Hopewell Jemma C JC Colhoun Helen M HM Kullo Iftikhar J IJ

Circulation. Genomic and precision medicine 20211004 5

<h4>Background</h4>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.<h4>Methods</h4>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 as ...[more]

PMID: 34601942

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Dataset Information

Genome-Wide Association Study of Peripheral Artery Disease.

Background

Methods

Results

Conclusions

Publications

Genome-Wide Association Study of Peripheral Artery Disease.

Similar Datasets

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