PITX2 and atrial fibrillation: Although the mechanism of action of these variants is still unclear, their genetic localization in an intergenic region, with the nearest gene, PITX2 (encodes the paired-like homeodomain transcription factor 2), 150 kilobases (kb) away, suggests a plausible role of both SNPs in the pathogenesis of AF [125,126] In fact, experimental studies in mice, including ours, demonstrated that Pitx2 is crucial for embryonic development, atria and sinus node formation/function, and left-right heart asymmetry [127,128,129].