SynthesisPloS one2022
Genome-wide and phenome-wide analysis of ideal cardiovascular health in the VA Million Veteran Program.
Synthesis in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Shared genetic architecture of posttraumatic stress disorder with cardiovascular imaging, risk, and diagnoses.Nature communications · 2025Article
- Exploring beyond diagnoses in electronic health records to improve discovery: a review of the phenome-wide association study.JAMIA open · 2025Review
- Causal effects of cardiovascular health on five epigenetic clocks.Clinical epigenetics · 2024Article
- Genetics of posttraumatic stress disorder and cardiovascular conditions using Life's Essential 8, Electronic Health Records, and Heart Imaging.medRxiv : the preprint server for health sciences · 2024Article
- Are ICD codes reliable for observational studies? Assessing coding consistency for data quality.Digital healthArticle
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Authors and funding
20 authors.
Funding
Abstract
backgroundGenetic studies may help identify causal pathways; therefore, we sought to identify genetic determinants of ideal CVH and their association with CVD outcomes in the multi-population Veteran Administration Million Veteran Program.
methodsAn ideal health score (IHS) was calculated from 3 clinical factors (blood pressure, total cholesterol, and blood glucose levels) and 3 behavioral factors (smoking status, physical activity, and BMI), ascertained at baseline. Multi-population genome-wide association study (GWAS) was performed on IHS and binary ideal health using linear and logistic regression, respectively. Using the genome-wide significant SNPs from the IHS GWAS, we created a weighted IHS polygenic risk score (PRSIHS) which was used (i) to conduct a phenome-wide association study (PheWAS) of associations between PRSIHS and ICD-9 phenotypes and (ii) to further test for associations with mortality and selected CVD outcomes using logistic and Cox regression and, as an instrumental variable, in Mendelian Randomization.
resultsThe discovery and replication cohorts consisted of 142,404 (119,129 European American (EUR); 16,495 African American (AFR)), and 45,766 (37,646 EUR; 5,366 AFR) participants, respectively. The mean age was 65.8 years (SD = 11.2) and 92.7% were male. Overall, 4.2% exhibited ideal CVH based on the clinical and behavioral factors. In the multi-population meta-analysis, variants at 17 loci were associated with IHS and each had known GWAS associations with multiple components of the IHS. PheWAS analysis in 456,026 participants showed that increased PRSIHS was associated with a lower odds ratio for many CVD outcomes and risk factors. Both IHS and PRSIHS measures of ideal CVH were associated with significantly less CVD outcomes and CVD mortality.
conclusionA set of high interest genetic variants contribute to the presence of ideal CVH in a multi-ethnic cohort of US Veterans. Genetically influenced ideal CVH is associated with lower odds of CVD outcomes and mortality.
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