Genome-wide Association Study of Cardiovascular Traits in 6142 Sardinians

National Institute On Aging

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Abstract

1) SardiNIA participated in a genome-wide meta-analysis of 100 studies in up to 835,465 individuals and revealed 493 independent genetic variants in 352 loci. We prioritized 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provided insights in their ECG signature. Two-sample Mendelian randomization analyses indicated that higher genetically predicted RHR increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We did not find evidence for a linear or non-linear genetic association between RHR and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicated that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample Mendelian randomization analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of RHR biology and give additional insights in its role in cardiovascular disease development.