MTHFR and atrial fibrillation: However, these observations are in contradiction regarding the causal role of tHcy: the former could be viewed as evidence of the causal tHcy effect, potentially indicating that tHcy concentration does not critically depend on MTHFR 677C>T, whereas the latter resulted in a two-sample MR analysis claiming no causal effect of tHcy on (NV)AF [19].