Dataset Information

Genome Wide Epistasis Study of On-Statin Cardiovascular Events with Iterative Feature Reduction and Selection.

ABSTRACT: Predicting risk for major adverse cardiovascular events (MACE) is an evidence-based practice that incorporates lifestyle, history, and other risk factors. Statins reduce risk for MACE by decreasing lipids, but it is difficult to stratify risk following initiation of a statin. Genetic risk determinants for on-statin MACE are low-effect size and impossible to generalize. Our objective was to determine high-level epistatic risk factors for on-statin MACE with GWAS-scale data. Controlled-access data for 5890 subjects taking a statin collected from Vanderbilt University Medical Center's BioVU were obtained from dbGaP. We used Random Forest Iterative Feature Reduction and Selection (RF-IFRS) to select highly informative genetic and environmental features from a GWAS-scale dataset of patients taking statin medications. Variant-pairs were distilled into overlapping networks and assembled into individual decision trees to provide an interpretable set of variants and associated risk. 1718 cases who suffered MACE and 4172 controls were obtained from dbGaP. Pathway analysis showed that variants in genes related to vasculogenesis (FDR = 0.024), angiogenesis (FDR = 0.019), and carotid artery disease (FDR = 0.034) were related to risk for on-statin MACE. We identified six gene-variant networks that predicted odds of on-statin MACE. The most elevated risk was found in a small subset of patients carrying variants in COL4A2, TMEM178B, SZT2, and TBXAS1 (OR = 4.53, p < 0.001). The RF-IFRS method is a viable method for interpreting complex "black-box" findings from machine-learning. In this study, it identified epistatic networks that could be applied to risk estimation for on-statin MACE. Further study will seek to replicate these findings in other populations.

SUBMITTER: Adams SM

PROVIDER: S-EPMC7712544 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Genome Wide Epistasis Study of On-Statin Cardiovascular Events with Iterative Feature Reduction and Selection.

Adams Solomon M SM Feroze Habiba H Nguyen Tara T Eum Seenae S Cornelio Cyrille C Harralson Arthur F AF

Journal of personalized medicine 20201107 4

Predicting risk for major adverse cardiovascular events (MACE) is an evidence-based practice that incorporates lifestyle, history, and other risk factors. Statins reduce risk for MACE by decreasing lipids, but it is difficult to stratify risk following initiation of a statin. Genetic risk determinants for on-statin MACE are low-effect size and impossible to generalize. Our objective was to determine high-level epistatic risk factors for on-statin MACE with GWAS-scale data. Controlled-access data ...[more]

PMID: 33171725

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Project description:Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10(-8) as significant.Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6). Among migraineurs with aura rs7698623 in MEPE (OR?=?6.37; 95% CI 3.15-12.90; p?=?2.7×10(-7)) and rs4975709 in IRX4 (OR?=?5.06; 95% CI 2.66-9.62; p?=?7.7×10(-7)) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR?=?3.05; 95% CI 1.98-4.69; p?=?4.3×10(-7)), and the intergenic rs1406961 with CVD death (OR?=?12.33; 95% CI 4.62-32.87; p?=?5.2×10(-7)). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR?=?4.67; 95% CI 2.53-8.62; p?=?8.0×10(-7)).Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research.

Dataset Information

Genome Wide Epistasis Study of On-Statin Cardiovascular Events with Iterative Feature Reduction and Selection.

Publications

Genome Wide Epistasis Study of On-Statin Cardiovascular Events with Iterative Feature Reduction and Selection.

Similar Datasets

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