Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Editorial boards of dermatology journals and their potential financial conflict of interest

Background: Financial relationships between editorial board members of peer-reviewed journals and pharmaceutical and medical device manufacturing companies can potentially lead to biases and loss of objectivity of the medical literature. The purpose of this study was to evaluate the potential financial conflicts of interest that exist among editorial board members of dermatology journals.Methods: Editorial board members for 36 dermatology journals were identified and searched using the Open Payments database on the Center for Medicare and Medicaid Services website. The total amount of general payments made to these physician editors were collected and stratified using a tier system: 1) nothing reported, 2) &gt;0 and <10,000, 3) &gt;10,000 and <100,000, and 4) &gt;$100,000.Results: We identified 551 editors from 36 dermatology journals for use in our analysis. Some form of general payment was made to 87$100,000.Conclusions: Financial relationships exist between editorial board members of dermatology journals and pharmaceutical/medical device manufacturing companies, which could lead to financial conflicts of interest. Publications coming from journals with highly paid physician editors have more potential to be biased

Editorial boards of dermatology journals and their potential financial conflict of interest

Background: Financial relationships between editorial board members of peer-reviewed journals and pharmaceutical and medical device manufacturing companies can potentially lead to biases and loss of objectivity of the medical literature. The purpose of this study was to evaluate the potential financial conflicts of interest that exist among editorial board members of dermatology journals.Methods: Editorial board members for 36 dermatology journals were identified and searched using the Open Payments database on the Center for Medicare and Medicaid Services website. The total amount of general payments made to these physician editors were collected and stratified using a tier system: 1) nothing reported, 2) &gt;0 and <10,000, 3) &gt;10,000 and <100,000, and 4) &gt;$100,000.Results: We identified 551 editors from 36 dermatology journals for use in our analysis. Some form of general payment was made to 87$100,000.Conclusions: Financial relationships exist between editorial board members of dermatology journals and pharmaceutical/medical device manufacturing companies, which could lead to financial conflicts of interest. Publications coming from journals with highly paid physician editors have more potential to be biased

Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream

This randomized, double-blind, placebo-controlled trial examined the use of topical fluorouracil, 5%, to prevent keratinocyte carcinoma

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85–0.92, p = 6.3 × 10−10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49–0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D