Our approach effectively replicated the strongest previously known association with cleft lip—the one with IRF6—in both populations and by both methods, and suggested new associations with ADH1C and PDGFC. Finally, the novel genes detected here (MKX, ALX3, ETV5, and FGF12) provide new insights for future analyses of this common and complex birth defect. Here, ALX3 is linked to cleft lip.