TBX5 and Holt-Oram syndrome: Holt-Oram syndrome is partially caused by variants in the TBX5 gene [43, 44], and GWAS studies on AF have shown several significant loci with nearest genes known to be important for heart development and causal for CHD, such as NKX2-5, GATA4, GJA1, and GJA5 [11, 45].