Genetic risk factors for orofacial clefts in Central Africans and Southeast Asians.

Genome-wide association studies (GWAS) for orofacial clefts have identified several susceptibility regions, but have largely focused on non-Hispanic White populations in developed countries. We performed a targeted genome-wide study of single nucleotide polymorphisms (SNPs) in exons using the Illumina HumanExome+ array with custom fine mapping of 16 cleft susceptibility regions in three underserved populations: Congolese (87 case-mother, 210 control-mother pairs), Vietnamese (131 case-parent trios), and Filipinos (42 case-mother, 99 control-mother pairs). All cases were children with cleft lip with or without cleft palate. Families were recruited from local hospitals and parental exposures were collected using interviewer-administered questionnaires. We used logistic regression models for case-control analyses, family-based association tests for trios, and fixed-effect meta-analyses to determine individual SNP effects corrected for multiple testing. Of the 16 known susceptibility regions tested, SNPs in four regions reached statistical significance in one or more of these populations: 1q32.2 (IRF6), 10q25.3 (VAX1), and 17q22 (NOG). Due to different linkage disequilibrium patterns, significant SNPs in these regions differed between the Vietnamese and Filipino populations from the index SNP selected from previous GWAS studies. Among Africans, there were no significant associations identified for any of the susceptibility regions. rs10787738 near VAX1 (P = 4.98E-3) and rs7987165 (P = 6.1E-6) were significant in the meta-analysis of all three populations combined. These results confirm several known susceptibility regions and identify novel risk alleles in understudied populations.

Effectiveness of international surgical program model to build local sustainability.

Background. Humanitarian medical missions may be an effective way to temporarily overcome limitations and promote long-term solutions in the local health care system. Operation Smile, an international medical not-for-profit organization that provides surgery for patients with cleft lip and palate, not only provides surgery through short-term international missions but also focuses on developing local capacity. Methods. The history of Operation Smile was evaluated globally, and then on a local level in 3 countries: Colombia, Bolivia, and Ethiopia. Historical data was assessed by two-pronged success of (1) treating the surgical need presented by cleft patients and (2) advancing the local capacity to provide primary and ongoing care to patients. Results. The number of patients treated by Operation Smile has continually increased. Though it began by using only international teams to provide care, by 2012, this had shifted to 33% of patients being treated by international teams, while the other 67% received treatment from local models of care. The highest level of sustainability was achieved in Columbia, where two permanent centers have been established, followed by Bolivia and lastly Ethiopia. Conclusions. International missions have value because of the patients that receive surgery and the local sustainable models of care that they promote.