We identified three novel loci, KANK4, LAMC1 and ATP1B1, for FECD, and demonstrated cellular expression of TCF4. Our results support a multifactorial model for disease aetiology with strong predictive power (AUC=0.78 from an oligogenic risk-score model), although variants in TCF4 alone do a commendable job of predicting risk in Caucasians. This evidence concerns the gene LAMC1 and Fuchs endothelial corneal dystrophy.