Genomic analyses in African populations identify novel risk loci for cleft palate

• Published in: Human molecular genetics Vol. 28; no. 6; pp. 1038 - 1051
• Main Authors: Butali, Azeez, Mossey, Peter A, Adeyemo, Wasiu L, Eshete, Mekonen A, Gowans, Lord J J, Busch, Tamara D, Jain, Deepti, Yu, Wenjie, Huan, Liu, Laurie, Cecelia A, Laurie, Cathy C, Nelson, Sarah, Li, Mary, Sanchez-Lara, Pedro A, Magee, William P, Magee, Kathleen S, Auslander, Allyn, Brindopke, Frederick, Kay, Denise M, Caggana, Michele, Romitti, Paul A, Mills, James L, Audu, Rosemary, Onwuamah, Chika, Oseni, Ganiyu O, Owais, Arwa, James, Olutayo, Olaitan, Peter B, Aregbesola, Babatunde S, Braimah, Ramat O, Oginni, Fadekemi O, Oladele, Ayodeji O, Bello, Saidu A, Rhodes, Jennifer, Shiang, Rita, Donkor, Peter, Obiri-Yeboah, Solomon, Arthur, Fareed Kow Nanse, Twumasi, Peter, Agbenorku, Pius, Plange-Rhule, Gyikua, Oti, Alexander Acheampong, Ogunlewe, Olugbenga M, Oladega, Afisu A, Adekunle, Adegbayi A, Erinoso, Akinwunmi O, Adamson, Olatunbosun O, Elufowoju, Abosede A, Ayelomi, Oluwanifemi I, Hailu, Taiye, Hailu, Abiye, Demissie, Yohannes, Derebew, Miliard, Eliason, Steve, Romero-Bustillous, Miguel, Lo, Cynthia, Park, James, Desai, Shaan, Mohammed, Muiawa, Abate, Firke, Abdur-Rahman, Lukman O, Anand, Deepti, Saadi, Irfaan, Oladugba, Abimibola V, Lachke, Salil A, Amendt, Brad A, Rotimi, Charles N, Marazita, Mary L, Cornell, Robert A, Murray, Jeffrey C, Adeyemo, Adebowale A
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.03.2019
• Subjects: Alleles; Animals; Association Studies; Black People - genetics; Chromosome Mapping; Cleft Palate - genetics; Disease Models, Animal; Enhancer Elements, Genetic; Female; Gene Expression; Gene Frequency; Genetic Predisposition to Disease; Genetics, Population; Genome, Human; Genome-Wide Association Study; Genomics - methods; Genotype; Humans; Male; Mice; Odds Ratio; Polymorphism, Single Nucleotide; Quantitative Trait Loci
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddy402

Abstract Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.