Genome-wide analysis refines the genetic architecture of orofacial clefts and identifies novel risk loci in the african population.
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Unilag Press, 2018
BACKGROUND: Orofacial clefts (OFCs) are the most common birth defects in the head and neck region, affecting one out of every 700 live births worldwide. These defects lead to significant financial, educational, medical, psychological, and cultural problems. OBJECTIVE: To conduct genome wide association study (GWAS) for OFC in Africa. METHODS: A total of 3,353 participants were genotyped on the pre-release consortium version of Illumina Multi Ethnic Genotyping Array (MEGA). Imputation was done into the 1000 Genomes Phase 3 reference imputation panel using IMPUTE2. The final dataset that passed quality control consisted of 3,178 participants enrolled from Ethiopia (30%), Ghana (43%), and Nigeria (27%). They included 814 cases of CLP, 205 cases of isolated CP, and 2,159 related and unrelated controls. Over 45million SNPs were imputed including the 2.2million SNPs in the Multi Ethnic Genotyping Array. Of these SNPs, only 16 million passed our quality control filter and were included in the final analyses. Given the known differences in the developmental and genetic basis of CL/P versus isolated CP, we conducted two separate GWAS (one for each phenotype). RESULTS: The GWAS for CL/P showed that the most significant hits are on chromosomes 8 and 3. The chromosome 8 locus (leading SNP, rs72728755, p = 1.52 × 10–6) is in the 8q.24 region that has been previously reported to be associated with CL/P in Europeans. The GWAS for isolated CP revealed one genome-wide significant locus on chromosome 2 (leading SNP rs140938806, p = 2.76 × 10–9). CONCLUSIONS: Our study has refined the genetic architecture of OFC in Africa, identified new loci and demonstrated genetic heterogeneity for the two cleft sub-phenotypes. This will lead to additional insights into craniofacial development and biology. Keywords: Orofacial clefts; GWAS, Africa
Orofacial clefts , GWAS , Africa , Research Subject Categories::ODONTOLOGY
Adeyemo WL, James O, Ogunlewe MO, Oseni GO. Jain D, Mossey PA, Busch T, Gowans LJJ, Eshete MA, Laurie CA, Olaitan PB, Aregbesola BS, Bello SA, Abdur-Rahman L, Marazita ML, Murray JC, Adeyemo AA, Butali A. Genome-wide analysis refines the genetic architecture of orofacial clefts and identifies novel risk loci in the african population. 13th Annual Conference and Fair, University of Lagos. August 2018. (Poster presentation).