Perceptions and beliefs of community gatekeepers about genomic risk information in African cleft research.

BACKGROUND: A fundamental ethical issue in African genomics research is how socio-cultural factors impact perspectives, acceptance, and utility of genomic information, especially in stigmatizing conditions like orofacial clefts (OFCs). Previous research has shown that gatekeepers (e.g., religious, political, family or community leaders) wield considerable influence on the decision-making capabilities of their members, including health issues. Thus, their perspectives can inform the design of engagement strategies and increase exposure to the benefits of genomics testing/research. This is especially important for Africans underrepresented in genomic research. Our study aims to investigate the perspectives of gatekeepers concerning genomic risk information (GRI) in the presence of OFCs in a sub-Saharan African cohort. METHODS: Twenty-five focus group discussions (FGDs) consisting of 214 gatekeepers (religious, community, ethnic leaders, and traditional birth attendants) in Lagos, Nigeria, explored the opinions of participants on genomic risk information (GRI), OFC experience, and the possibility of involvement in collaborative decision-making in Lagos, Nigeria. Transcripts generated from audio recordings were coded and analyzed in NVivo using thematic analysis. RESULTS: Three main themes-knowledge, beliefs, and willingness to act-emerged from exploring the perspective of gatekeepers about GRI in this group. We observed mixed opinions regarding the acceptance of GRI. Many participants believed their role is to guide and support members when they receive results; this is based on the level of trust their members have in them. However, participants felt they would need to be trained by medical experts to do this. Also, religious and cultural beliefs were crucial to determining participants' understanding of OFCs and the acceptance and utilization of GRI. CONCLUSIONS: Incorporating cultural sensitivity into public engagement could help develop appropriate strategies to manage conflicting ideologies surrounding genomic information in African communities. This will allow for more widespread access to the advances in genomics research in underrepresented populations. We also recommend a synergistic relationship between community health specialists/scientists, and community leaders, including spiritual providers to better understand and utilize GRI.

Parents and Provider Perspectives on the Return of Genomic Findings for Cleft Families in Africa.

BACKGROUND: Inadequate knowledge among health care providers (HCPs) and parents of affected children limits the understanding and utility of secondary genetic findings (SFs) in under-represented populations in genomics research. SFs arise from deep DNA sequencing done for research or diagnostic purposes and may burden patients and their families despite their potential health importance. This study aims to evaluate the perspective of both groups regarding SFs and their choices in the return of results from genetic testing in the context of orofacial clefts. METHODS: Using an online survey, we evaluated the experiences of 252 HCPs and 197 parents across participating cleft clinics in Ghana and Nigeria toward the return of SFs across several domains. RESULTS: Only 1.6% of the HCPs felt they had an expert understanding of when and how to incorporate genomic medicine into practice, while 50.0% agreed that all SFs should be returned to patients. About 95.4% of parents were willing to receive all the information from genetic testing (including SFs), while the majority cited physicians as their primary information source (64%). CONCLUSIONS: Overall, parents and providers were aware that genetic testing could help in the clinical management of diseases. However, they cited a lack of knowledge about genomic medicine, uncertain clinical utility, and lack of available learning resources as barriers. The knowledge gained from this study will assist with developing guidelines and policies to guide providers on the return of SFs in sub-Saharan Africa and across the continent.

Using machine learning algorithms to investigate factors associated with complete edentulism among older adults in the United States.

AIMS: Edentulism is an incapacitating condition, and its prevalence is unequal among different population groups in the United States (US) despite its declining prevalence. This study aimed to investigate the current prevalence, apply Machine Learning (ML) Algorithms to investigate factors associated with complete tooth loss among older US adults, and compare the performance of the models. METHODS: The cross-sectional 2020 Behavioral Risk Factor Surveillance System (BRFSS) data was used to evaluate the prevalence and factors associated with edentulism. ML models were developed to identify factors associated with edentulism utilizing seven ML algorithms. The performance of these models was compared using the area under the receiver operating characteristic curve (AUC). RESULTS: An overall prevalence of 11.9% was reported. The AdaBoost algorithm (AUC = 84.9%) showed the best performance. Analysis showed that the last dental visit, educational attainment, smoking, difficulty walking, and general health status were among the top factors associated with complete edentulism. CONCLUSION: Findings from our study support the declining prevalence of complete edentulism in older adults in the US and show that it is possible to develop a high-performing ML model to investigate the most important factors associated with edentulism using nationally representative data.

Investigating the relationship between cancer and orofacial clefts using GWAS significant loci for cancers: A case-control and case-triad study.

Background: Several population-based case-control studies have reported concurrent presentation of cancer and congenital malformations. Many associations have been made between oral clefting and cancers, though some of these results are conflicting. Some studies have reported an increased risk of cancer among 1st-degree relatives of cleft cases and vice versa, and also an excess risk of cancers of the breast, lung, and brain among those with oral clefts. This study aimed to determine if the genetic polymorphisms found in some cancers are also associated with orofacial cleft in an African cohort. Methods: The study was a case-control and case-triad study in which cases were 400 individuals clinically diagnosed with non-syndromic cleft lip and/or palate (CL/P), while controls were 450 individuals without CL/P. Samples were obtained from three African countries while DNA extraction, PCR, and genotyping were carried out at the University of Iowa, US. Eleven SNPs in genes coding for SWI/SNF subunits and 13 GWAS significant SNPs for cancers associated with orofacial cleft were selected. Case-control analysis, transmission disequilibrium test (TDT), and DFAM to combine the parent-offspring trio data and unrelated case/control data in a single analysis were carried out using PLINK. Results: For the case-control analyses that included all the clefts and for the CLP subtype, none of the SNPs were statistically significant. Statistically increased risk for the following SNPs rs34775372 (p = 0.02; OR = 1.54, CI:1.07-2.22), rs55658222 (p = 0.009; OR = 2.64, CI:1.28-5.45) and rs72728755 (p = 0.02; OR=2.27, CI:1.17-4.45) was observed with the CL only sub-group. None of these were significant after Bonferoni correction. In the TDT analyses, a significantly reduced risk with rs10941679 (p = 0.003; OR = 0.43, CI:0.24-0.75) was observed and this was significant after Bonferroni correction. The rs10941679 was also significant (p = 0.003) in the DFAM analyses as well even after Bonferroni correction. Conclusion: The results from this study represent an important starting point for understanding the concurrent presentation of some cancers in orofacial clefts, and cancer risks in cleft patients. The associations observed warrant further investigation in a larger cohort and will set the stage for a more mechanistic approach toward understanding the risk for cancers in families with clefts.