The P-wave duration (PWD) is an electrocardiographic measurement that represents atrial conduction. Prolonged or shortened PWD is associated with atrial fibrillation (AF). Exome-chip data was utilized to examine the associations between rare and common variants with PWD. In total, fifteen studies incorporating 64,440 individuals (630 Asian, 1186 Hispanic, 5681 African, and 56,943 European) and approximately 230 thousand variants were used to investigate associations with maximum PWD across the 12-lead ECG.
Sequence kernel and gene-based burden association tests examined the low-frequency variant-PWD associations. Meta-analyses summarized the association results for common variants. Additionally, associations between AF and PWD loci were also examined, using previous AF genome-wide association studies. 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD were identified, including several AF loci (RPL3L, MYH6, TTN, TBX5, SOX5, SYNPO2L, CAND2, CAV1, PITX2, and SCN10A). The top variants at known sarcomere genes (MYH6, TTN) were associated with higher AF risk and longer PWD. However, top variants at other loci (e.g., SCN10A and PITX2) were associated with lower AF risk and longer PWD.
In conclusion, we identified 14 novel loci in standard and low-frequency variant analyses and six gene regions in a low-frequency variant analysis for PWD. The results obtained underscore the shared mechanisms of AF and atrial conduction, and highlight multiple novel genetic loci associated with PWD.
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