Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of genes important to bone biology in general, and particularly for identifying components unique to intramembranous ossification, which cannot be captured at other skeletal sites. We assessed genetic determinants of SK-BMD in 43,800 individuals, identifying 59 genome-wide significant loci (4 novel), explaining 12.5% of its variance. Pathway and enrichment analyses of the association signals resulted in clustering within gene-sets involved in regulating the development of the skeleton; overexpressed in the musculoskeletal system; and enriched in enhancer and transcribed regions in osteoblasts. From the four novel loci (mapping to ZIC1, PRKAR1A, ATP6V1C1, GLRX3), two (ZIC1 and PRKAR1A) have previously been related to craniofacial developmental defects. Functional validation of skull development in zebrafish revealed abnormal cranial bone initiation that culminated in ectopic sutures and reduced BMD in mutated zic1 and atp6v1c1 fish and asymmetric bone growth and elevated BMD in mutated prkar1a fish. We confirmed a role of ZIC1 loss-of-function in suture patterning and discovered ATP6V1C1 gene associated with suture development. In light of the evidence presented suggesting that SK-BMD is genetically related to craniofacial abnormalities, our study opens new avenues to the understanding of the pathophysiology of craniofacial defects and towards the effective pharmacological treatment of bone diseases.
A significant number of banks folded up during the Ghanaian banking financial crisis of 2017 to 2018 causing significant social costs as well as impeding economic growth. We take a step backward to present the significant drivers of the profitability of banks in Ghana. Obtaining panel data from the banks’ websites, the Ghana Statistical Service (GSS), and the Ghana Stock Exchange (GSE), the regression analysis was used to assess the drivers of profitability of banks in Ghana. The findings show that the bank-specific variables had no combined effect on profitability. Hence, the study concludes that the bank-specific variables do not have a significant influence on the performance of the Ghanaian listed banks. On the other hand, some of the external factors were observed to have a significant influence on profitability. The findings further showed that the drivers of profitability of the Ghanaian banks were, inflation, capital adequacy, and monetary policy. Since these are all external factors, the banks must learn how to predict and anticipate the external factors and make adjustments in their operations to enable them to improve profitability. While this study recommends to the managers of Ghanaian banks to be cautious in their operational decisions, the economy must also be managed soundly to ensure the growth of banks and hopefully avoid future crises.
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