In PLOS Genetics, researchers from the University of North Carolina-Chapel Hill and elsewhere explore the complex functional effects of different variants linked to the glucose regulation-related hormone adiponectin in a past genome-wide association study. With conditional analyses, reporter assays, expression quantitative trait locus analyses, fine mapping, and other approaches, the team investigated variants at four adiponectin-related loci identified using genetic data for more than 9,200 non-diabetic male participants in the Metabolic Syndrome in Men study, uncovering examples of allelic heterogeneity and distinct expression effects for variants within specific loci. "Some GWAS loci are relatively straightforward, with a single association signal, functional variant, and mechanism," they report. "We demonstrate that multiple signals within a locus may also be functionally examined separately from each other, even when they are not statistically independent, and that multiple signals can exhibit distinct effects through multiple mechanisms and multiple transcripts."
A European team reporting in PLOS One outlines a pair of clear cell renal cell carcinoma (ccRCC) subtypes marked by distinct microRNA expression patterns. The researchers did small RNA sequencing on primary tumor, metastatic tumor, and/or matched normal samples collected from 128 ccRCC patients at Leuven University Hospitals, comparing that data to miRNA and expression profiles from ccRCC cases profiled for the Cancer Genome Atlas project. Their analysis highlighted two ccRCC clusters, including groups of miRNAs that appeared to track with survival patterns and with the four gene expression-based subtypes reported for ccRCC in the past. From these and other results, the authors point to "a general shift in miRNA expression in ccRCC, between more and less aggressive tumors."
Investigators at Umea University and other centers in Sweden report on regional differences detected by whole-genome sequencing of individuals from a relatively unpopulated region in northern Sweden for another paper in PLOS One. The team did whole-genome sequencing on 300 individuals from Västerbotten County to complement population results previously reported from southern Sweden. Along with genetic differentiation from populations in southern Sweden, they saw signs of population structure within the area, apparently reflecting the region's demographic patterns. "Historically, the inland region has predominantly been inhabited by the indigenous Sami population, but settlement programs were initiated by the state during the mid- to late-17th century," the authors write, arguing that the new genome sequence collection "provides a high-resolution map of the genetic variation which agrees with earlier studies of protein markers and marriage patterns."