eQTL Set–Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma

BACKGROUND: Over 20 susceptibility single-nucleotide polymorphisms (SNPs) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), explaining a small portion of heritability. METHODS: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTLs), and set-based SKAT association using selected eQTLs that predict the gene expression. RESULTS: While the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641 and HSP90AA1). CONCLUSIONS: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set based genetic association approach. IMPACT: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set based genetic association approach as an alternative method for TWAS analysis

Multi-epoch monitoring of TXS 0506+056 with MAGIC and MWL partners

The measurement of an astrophysical flux of high-energy neutrinos by IceCube is an important step towards finding the long-sought sources of cosmic rays. Nevertheless, the long exposure neutrino sky map shows no significant indication of point sources so far. The real-time follow- up of neutrino events turned out to be the most successful approach in neutrino point-source searches. It brought, among others, the most compelling evidence for a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 in coincidence with a single high-energy neutrino from IceCube (IceCube-170922A). The fast multiwavelength(MWL) follow-up of this alert was key for establishing this coincidence and constraining the subsequent theoretical modeling for this event. In the long run, accurate and contemporaneous MWL spectral measurements are essential ingredients in investigating the physical processes leading to particle acceleration and emission of radiation. A deeper understanding of those processes allows us to put constraints on the potential neutrino emission. Here we present the light curves and simultaneous spectral energy distributions from November 2017 till February 2021 of MAGIC and MWL monitoring of TXS 0506+056. The more than two-year-long rise and high state of the radio light curve of TXS 0506+056, which started near the time of the IceCube neutrino detection, seems to have ended, as indicated by a steep decrease in the first half of 2021. We also present the theoretical interpretation of our observations