The best genetic predictors of heart arrhythmia and hidden comorbidity riken_en NatureGenet
. Our study also demonstrated that, in addition to the predictive ability for AF itself, AF-PRS segregated individuals with AF-related phenotypes, such as early onset of AF and cardioembolic stroke, and those with increased risks of long-term cardiovascular and stroke mortalities. This indicated that the cumulative genetic risk for AF could be an indicator for early therapeutic intervention, including anticoagulation in at-risk individuals as a primary prevention of stroke.
Finally, MR analysis revealed evidence of a causal relationship between AF and relevant diseases or traits, which supports the results from clinical observational studies. In particular, blood pressure was the only trait that showed significant causality among atherosclerotic- and metabolic-related traits, which indicates that blood pressure is an important modifiable risk factor, and the intensive management of blood pressure may reduce the risk of AF development.
In conclusion, our large-scale Japanese and cross-ancestry genetic analyses identified 35 new risk loci and provided insights into the distinct and shared genetic architecture of AF between Japanese and Europeans. Integrative analysis of transcriptome and epigenome data highlighted candidate genes and implicated a transcription factor involved in the mechanism of disease development.
For GWAS quality control , we excluded samples with a call rate 0.2 by PLINK 2.0 . We then excluded samples with a heterozygosity rate > +4 s.d. To identify population stratification, we performed principal component analysis using PLINK 2.0 and excluded outliers from the Japanese cluster. For the case samples in GWAS, we selected individuals with AF or atrial flutter diagnosed by a physician based on the general medical practices or documented on a 12-lead electrocardiogram.
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