Non-syndromic orofacial clefts are one of the most common birth defects worldwide. Genetic variation is thought to play a major role in risk of non-syndromic clefts; indeed, several genetic risk loci have been identified, to date. However, these loci cumulatively explain only part of the heritability, and for most of these loci, the specific causal variants have not yet been determined. Moreover, recent work has suggested that subclinical cleft-related phenotypes may comprise part of the cleft phenotypic spectrum, and may serve as indicators of the underlying cleft liability. The genetics of such cleft-related phenotypes is not well understood. This proposal will seek to fill the gap in knowledge regarding the genetic variants leading to overt forms of clefts and related subclinical phenotypes. In this CIDR access proposal we request genotyping services for our previously collected cohort comprising cases with orofacial clefts, their immediate family members, and controls with no history of clefts. We will use these data to perform genome-wide association studies for orofacial clefts, cleft subtypes (e.g., cleft lip alone, cleft lip and palate, cleft palate alone), and related subclinical phenotypes. Understanding the genetic architecture of orofacial clefts and related subclinical features may ultimately lead to improved prediction of risk and recurrence, and may inform new preventive or therapeutic interventions.