German researchers have shown that white-striped leaves in an EMS-mutagenized barley line arise only when recessive mutations at two epistatic loci, var4 and var5, are combined, pointing to candidate

Single-cell RNA-sequencing shows that cell-type-specific expression quantitative trait loci drive much of complex trait heritability, highlighting cell-type-specific gene regulation as key to lin...

An introduction to the series Dwelling in Place which proposes a relational and active practice of dwelling that engages human and non-human actors in a shared temporal and spatial history.

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High-resolution real-time imaging of enhancer-promoter communication reveals how the two genomic loci are actively brought together through cohesin-mediated loop extrusion and how E-P interactions are temporally coordinated with transcriptional bursts. Unexpectedly, components of the RNA Pol II general machinery form nanoscale clusters at distal enhancers, and embedding the promoter into such clusters boosts GTF activities and triggers burst initiation.

We now take for granted the idea that a genome-wide association study, or GWAS, can help identify genetic variants associated with complex traits. Such studies have identified loci associated with everything from breast cancer to heart disease to diabetes.

A major goal of speciation research is identifying loci that underpin barriers to gene flow. Population genomics takes a ‘bottom-up’ approach, scanning the genome for molecular signatures of…

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Aims/hypothesis The human pancreas is a central organ for metabolic regulation that is comprised of diverse cell types that uniquely contribute to its function. Previous studies have performed expression quantitative trail loci (eQTL) discovery in either whole pancreas or in pancreatic islets, but due to differences between pancreatic cell types, this approach does not reveal cell type-specific effects. In this study, we sought to either implicate the cell type of action for known eQTLs or identify new eQTLs that may have been masked in bulk studies by performing eQTL discovery in individual pancreatic cell types. Methods We clustered 153,018 single-cell RNA sequencing (scRNA-seq) data from 71 pancreatic islet donors from the Human Pancreas Analysis Program (HPAP). We performed eQTL discovery in six pancreatic cell types using this resource directly. We further utilized this single cell resource as a reference to deconvolute bulk pancreatic RNA sequencing data from 305 Genotype Tissue Expression (GTEx) project donors and performed eQTL discovery in four pancreatic cell types. Finally, we performed fine-mapping and co-localization of pancreatic cell type eQTLs with metabolic GWAS to connect our findings to metabolic disease risk. Results From analyzing 71 individuals with single cell profiles, we identified 112 unique eGenes across six pancreatic cell types, 99 of which had been identified previously and 13 unique to this study. From the deconvoluted eQTLs, we identified 3,134 unique eGenes across four pancreatic cell types, 116 of which were unique to our study. Fine-mapping and co-localization of eQTLs with metabolic GWAS yielded key leads that warrant further investigation, such as the association of rs2168101 with LMO1 expression in alpha cells. Conclusions/interpretation We identified new signals that were previously not found in bulk pancreatic eQTL studies and potential cell type of action for several signals that were identified previously. Although there are limitations to the power, and therefore, discoverability of this study, it provides insights into how individual pancreatic cells differently contribute to metabolic disease. What is already known about this subject? What is the key question? What are the new findings? How might this impact clinical practice in the foreseeable future? ### Competing Interest Statement The authors have declared no competing interest. * ABF : approximate bayes factor eGene : gene associated with an eQTL eQTL : expression quantitative trait loci eVariant : variant associated with an eQTL FDR : false discovery rate GTEx : Genotype Tissue Expression project GWAS : genome-wide association study HPAP : Human Pancreas Analysis Program PPH4 : posterior probability of hypothesis four scRNA-seq : single cell RNA sequencing TPM : transcripts per million UMI : unique molecular identifier WGS : whole genome sequencing WHR : waist-hip-ratio WHRadjBMI : waist-hip-ratio adjusted for BMI National Institute of Diabetes and Digestive and Kidney Diseases, https://ror.org/00adh9b73, DK138512, DK140340 National Institute of Diabetes and Digestive and Kidney Diseases, https://ror.org/00adh9b73, UC4-DK112217, U01-DK123594, UC4-DK112232, U01-DK123716 NIH Common Fund, https://ror.org/001d55x84, R01 HD056465, UM1 DK126194 Daniel B Burke Endowed Chair for Diabetes Research