Genome-Wide Association Study of Non-syndromic Orofacial Clefts in a Multiethnic Sample of Families and Controls Identifies Novel Regions

MORENO-URIBE, LINA; MUÑETON, CLAUDIA P. RESTREPO; CHRISTENSEN, KAARE; HECHT, JACQUELINE T.; ADEYEMO, WASIU L.; MURRAY, JEFFREY C.; MARAZITA, MARY L.; FEINGOLD, ELEANOR; VALENCIA-RAMIREZ, LUZ CONSUELO; DELEYIANNIS, FREDERIC; ORIOLI, IEDA M.; BUTALI, AZEEZ; SHAFFER, JOHN R.; LESLIE, ELIZABETH J.; MUKHOPADHYAY, NANDITA; WEHBY, GEORGE; PADILLA, CARMENCITA; POLETTA, FERNANDO A.; BUXÓ, CARMEN J.; VIEIRA, ALEXANDRE R.; WEINBERG, SETH M.

Frontiers in Cell and Developmental Biology

Frontiers Media S.A.

Año: 2021 vol. 9

Orofacial clefts (OFCs) are among the most prevalent craniofacial birth defects worldwide and create a significant public health burden. The majority of OFCs are non-syndromic and vary in prevalence by ethnicity. Africans have the lowest prevalence of OFCs (~ 1/2,500), Asians have the highest prevalence (~1/500), Europeans and Latin Americans lie somewhere in the middle (~1/800 and 1/900, respectively). Thus, ethnicity appears to be a major determinant of the risk of developing OFC. The Pittsburgh Orofacial Clefts Multiethnic study was designed to explore this ethnic variance, comprising a large number of families and individuals (~12,000 individuals) from multiple populations worldwide: US and Europe, Asians, mixed Native American/Caucasians, and Africans. In this current study, we analyzed 2,915 OFC cases, 6,044 unaffected individuals related to the OFC cases, and 2,685 controls with no personal or family history of OFC. Participants were grouped by their ancestry into African, Asian, European, and Central and South American subsets, and genome-wide association run on the combined sample as well as the four ancestry-based groups. We observed 22 associations to cleft lip with or without cleft palate at 18 distinct loci with p-values < 1e-06, including 10 with genome-wide significance (