Genome-wide study of gene-by-sex interactions identifies risks for cleft palate.

Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP. CL/P is more common in males and CP is more frequently observed in females, so we hypothesized there would also be sex-specific differences for CP. Using a trio-based cohort, we performed sex-stratified genome-wide association studies (GWAS) based on proband sex followed by a genome-wide gene-by-sex (GxS) interaction testing. There were 13 loci significant for GxS interactions, with the top finding in LTBP1 (RR=3.37 [2.04 - 5.56], p=1.93x10 -6 ). LTBP1 plays a role in regulating TGF-B bioavailability, and knockdown in both mice and zebrafish lead to craniofacial anomalies. Further, there is evidence for differential expression of LTBP1 between males and females in both mice and humans. Therefore, we tested the association between the imputed genetically regulated gene expression of genes with significant GxS interactions and the CP phenotype. We found significant association for LTBP1 in cell cultured fibroblasts in female probands (p=0.0013) but not in males. Taken altogether, we show there are sex-specific risks for CP that are otherwise undetectable in a combined sex cohort, and LTBP1 is a candidate risk gene, particularly in females.

Qualitative Assessment of Surgical Repair of Three Types of Unilateral Cleft Lip

Abstract Objective: To assess the effect of the three types of unilateral cleft lip (UCL) [cleft lip only, cleft lip and alveolus, and cleft lip alveolus and palate] on the outcome of the repair. Material and Methods: This study was a case series of effect of types of UCL on the outcome of the repair. Fifteen subjects each were in three UCL phenotypes groups. Evaluation of the scar, lip, and nose was done qualitatively by both parents/guardians and professionals using a modified form of the criteria described by Christofides et al. (2006). Results: In the assessment of the surgical scar, the parents found a difference between the three types of cleft in terms of texture, shape, and width of the scar and presence of columella deviation. The professional assessors, however, only found the three types of cleft to be different in the presence of alar flattening. Conclusion: Differences truly exist in the outcome of surgical repair of the three types of unilateral cleft lip, especially in the aesthetics of the nose and in the width and shape of the residual lip scar. Thus, it is important to consider this in the assessment of UCL repair because putting the subtypes together might have a negative impact on the assessment.

A preprogram appraisal of factors influencing research productivity among faculty at college of medicine, University of Lagos

A defining feature of any university is its dedication to scholarly activities, leading to the generation of knowledge and ideas Research productivity is a measure of achievement of a scholar. The number of research publications in peer-reviewed journals is an important criterion for assessing productivity and prestige in the academia. Aims and Objectives: This cross-sectional descriptive study assessed the level of research productivity (RP) among junior faculty at the College of Medicine, University of Lagos, and investigated factors affecting their research output prior to the implementation of a 5-year training grant funded by the National Institutes of Health. Methods: Seventy junior faculty members attended a pre-program training, and the self-reported number of peer-reviewed publications (PRPs) was used as an indicator. Intrinsic and extrinsic factors influencing RP among the attendees were assessed and ranked. Results: The majority (42/70, 60%) of the respondents had <10 PRPs. The median (interquartile range) number of PRPs was 7 (3­18). A desire for the development of their personal skills, contribution to society, and personal research interests topped the list of intrinsic factors influencing RP. Work flexibility, research autonomy, and scholarly pursuits were the bottom three. A desire for promotion, respect from peers, and increased social standing were the top three extrinsic factors, while monetary incentives, employment opportunities, and the need to attend conferences were the lowest three. The top barriers to RP were lack of resources and lack of mentoring. Perceived older age, lack of time, and motivation were the lowest three barriers. Older age and professional cadre were associated with increased RP (P < 0.05). Conclusion: Among the participants, research output appears to be motivated primarily by a desire for personal development,promotion, and respect from peers. Lack of access to resources was the main barrier to increased RP. These factors may need to be considered when developing programs designed to promote RP