Genetic Contribution for Non-Syndromic Cleft Lip With or Without Cleft Palate (NS CL/P) in Different Regions of Brazil and Implications for

Non-syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (SantarFortaleza, Barbalha, Maceiand Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santar� (44%) and the lowest in Macei� (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarem (71%), Rio de Janeiro (70%), Fortaleza (64%), and Macei� (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5-1.6%, varying according to the location studied (0.6-0.7% in Maceio 2.2-2.8% in Barbalha). Our findings show that the degree of genetic contri- bution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consan- guinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analysesandshowthatcaremustbetakenwhenpoolingsamples from different populations for association studies.