Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Genetic characterization of Strongyloides fuelleborni infecting free-roaming African vervets (Chlorocebus aethiops sabaeus) on the Caribbean island of St. Kitts

Human strongyloidiasis is an important neglected tropical disease primarily caused by the nematode Strongyloides stercoralis, and to a lesser extent Strongyloides fuelleborni which mainly infects non-human primates. Zoonotic sources of infection have important implications for control and prevention of morbidity and mortality caused by strongyloidiasis. Recent molecular evidence suggests that for S. fuelleborni, primate host specificity is variable among genotypes across the Old World, and consequently that these types likely vary in their capacity for human spillover infections. Populations of free-roaming vervet monkeys (Chlorocebus aethiops sabaeus), introduced to the Caribbean Island of Staint Kitts from Africa, live in close contact with humans, and concern has arisen regarding their potential to serve as reservoirs of zoonotic infections. In this study, we sought to determine the genotypes of S. fuelleborni infecting St. Kitts vervets to explore whether they are potential reservoirs for human-infecting S. fuelleborni types. Fecal specimens were collected from St. Kitts vervets and S. fuelleborni infections were confirmed microscopically and by PCR. Strongyloides fuelleborni genotypes were determined from positive fecal specimens using an Illumina amplicon sequencing-based genotyping approach targeting the mitochondrial cox1 locus and 18S rDNA hypervariable regions I and IV of Strongyloides species. Phylogenetic analysis of resultant genotypes supported that S. fuelleborni from St. Kitts vervets is of an exclusively African variety, falling within the same monophyletic group as an isolate which has been detected previously in a naturally infected human from Guinea-Bissau. This observation highlights that St. Kitts vervets may serve as potential reservoirs for zoonotic S. fuelleborni infection, which warrants further exploration