Genome Biology - Insight into the genetic basis for many common autoimmune disorders has been uncovered by genome-wide association studies (GWAS), but this alone does not reveal causal variants,...

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Background The identification and characterisation of somatic cancer driver mutations in the non-coding genome remains challenging. Objective To broadly characterise non-coding driver mutations for p...

Background Over 1100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown. Results We execute a CRISPRi screen in human fetal osteoblasts (hFOBs) with single-cell RNA-seq read-out for 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci. The BMD relevance of hFOBs is supported by heritability enrichment from stratified LD-score regression involving 98 cell types grouped into 15 tissues. Twenty-three genes show perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping unexpectedly reveal that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues. Conclusions Our results provide a roadmap for how single-cell CRISPRi screens may be applied to the challenging task of resolving effector gene identities at all BMD GWAS loci. Extending our CRISPRi screening approach to other tissues could play a key role in fully elucidating the etiology of BMD.

The lag in funding extends far beyond D.E.I. initiatives, affecting almost every area of science: chemistry, computing, engineering, materials and more.

Huge reductions, if enacted, could have ‘catastrophic’ effects on US competitiveness and the scientific pipeline, critics say.

Dudek et al. use chromatin accessibility data in liver from 170 human donors to measure transcription factor binding at genetic variants. They observed 809 variants associated with binding. Given bind...

Dudek et al. use chromatin accessibility data in liver from 170 human donors to measure transcription factor binding at genetic variants. They observed 809 variants associated with binding. Given bind...

HHS would be asked to absorb a $40 billion cut, about one third of its discretionary budget.

If you want to appeal the decision, know the rules that govern terminations, as well as the specific rationale given in your notice, science policy experts say.

RFK Jr. plans to attend the funeral. He should apologize to the parents for his actions during a measles epidemic that likely involves thousands of children.

National Institutes of Health grants generated almost $95 billion in economic activity nationwide in FY 2024 according to a new report by United for Medical Research.

“Cost efficiency” order could block travel, supplies for labs and patient care

The order gives the Department of Government Efficiency more power over federal funds and spending practices.

Administration officials pressured the NIH to avoid clear advice from the agency’s own lawyers to restart grant funding now.

The National Institutes of Health had to stop considering new grant applications, delaying funding for research into diseases ranging from heart disease and cancer to Alzheimer's and allergies.

Its architect's daughter has cystic fibrosis—and benefits from a "miracle drug" backed by an agency he's attacking.

NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Supplemental Guidance to the 2024 NIH Grants Policy Statement: Indirect Cost Rates NOT-OD-25-068. OD

Researchers facing

The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal ant...