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Abstract
Background: Cardiovascular disease (CVD) is a primary global health issue with multiple risk factors.
Biochemical data and Genome-wide Association Studies (GWAS) have helped researchers
understand the mechanisms of how genetic variants affect biological pathways that
contribute to CVD phenotypes.
Methods: This study aims to identify genetic factors that influence the risk of CVD. We performed
a cross-sectional genetic study in 3,877 healthcare workers from Siriraj Hospital (the
SI-Health Study: SIH). The study conducted GWAS analysis on imputed genotyping data
fasting glucose, HbA1c, total cholesterol, triglycerides, HDL-C, LDL-C, diabetes,
hypertension, dyslipidemia, and family history of premature atherosclerosis, adjusted for
sex and age. We also assessed the replication of previously reported CVD-associated genes
from the GWAS catalog.
Results: Genome-wide association analysis identified 144 variants across 15 genes significantly
associated with quantitative traits, and 13 variants within 6 genes with dyslipidemia (p <
1×10ˉ8). APOE E2 allele (rs7412) was strongly associated with decreased LDL-C (-18.9
mg/dL) and total cholesterol (-14.4 mg/dL), demonstrating a protective effect against
dyslipidemia (odds ratio = 0.5), and with increased HDL-C (+4.5 mg/dL). APOA5 variant
rs662799 was associated with increased triglycerides (+12.6 mg/dL), while CETP variant
rs3764261 was associated with increased HDL-C (+3.8 mg/dL). ABCB11 variant rs139014876
was associated with decreased fasting blood glucose (-3.6 mg/dL). Approximately 70% of
previously reported strong associations in the GWAS catalog were replicated across all
examined traits.
Conclusions: These findings reveal complex genetic variants influencing CVD risk factors and emphasize
the importance of population-specific studies for improved prediction and personalized
prevention.
Harmony in health: Innovation for Sustainable Medicine 63