Researchers from the US and Lebanon profile somatic mutation patterns in dozens of glioblastoma (GBM) tumors from Lebanese patients in a study appearing in PLOS One. Using exome sequencing, the team assessed 60 patient-derived GBM tumor samples from 37 men and 23 women with the aggressive brain tumor type, looking in particular at mutational signatures and somatic variant patterns across 50 genes associated with GBM in other populations. In addition to spelling out the most frequently mutated genes in the GBM tumors at hand, the authors focused on NLRP5 gene mutations that appeared to correspond to poorer-than-usual patient outcomes, along with genes showing possible ties to tumor location. "Taken together," they write, "this report confirms several genetic associations with GBM and highlights the need for further studies with larger sample sizes to elucidate the mechanisms of proliferation, invasion, and treatment resistance in the context of GBM."
In PLOS Genetics, a Stanford University-led team reports on findings from a phenome-wide association study (PheWAS) focused on 60 phenotypic features associated with Marfan syndrome, DiGeorge syndrome, Noonan syndrome, or Alagille syndrome in almost 337,200 UK Biobank participants. Based on phenotypic clues that the researchers compiled from participant questionnaire data, hospital records, and physiological measurements, the researchers tracked down phenotype-genotype associations involving common variants in genes linked to each syndrome, including variants that appeared to coincide with traits such as blood pressure, body mass index, or height in individuals from the UK Biobank population. "Our findings suggest that common and rare alleles in syndromic disease genes are causative of individual component phenotypes present in a general population," they report, adding that "further research is needed to characterize the pleiotropic effects of alleles in syndromic genes in persons without the syndromic disease."
For another paper in PLOS Genetics, investigators in Denmark, Norway, Israel, and the US outline 16 loci linked to blood cytokine concentrations in Danish newborns. The team turned to available newborn blood spot samples collected in the first five days to a week after birth in nearly 9,500 infants in Denmark through the iPSYCH-Broad study for a genome-wide association study centered on concentrations for 10 cytokines in the blood, uncovering cytokine concentration-related variants at four new and a dozen known loci before mapping out related regulatory features. "[O]ur study sheds some light on the complex genetic architecture of inflammatory markers and highlights the important role of regulatory elements therein," the authors report, noting that comparisons with past studies on adults suggest that "mechanisms involved are relatively stable throughout life."