The PITX2 forms an incoherent regulatory circuit with TBX5 (significantly downregulated in the MACE-affected sibship; FC = −2.7); both regulate each other’s expression and also regulate the expression of their downstream targets antagonistically, and perturbation of this co-regulated network increases atrial fibrillation susceptibility [63,64,65]. This evidence concerns the gene PITX2 and atrial fibrillation.