doi.org

The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements - Nature Genetics

This Perspective explores the co-evolution of transposable elements and KRAB zinc-finger proteins in relation to their integration into human gene regulatory networks, highlighting their potential eff...

nature.com

The evolution of gene regulation in mammalian cerebellum development

Gene regulatory changes are considered major drivers of evolutionary innovations, including the cerebellum’s expansion during human evolution, yet they remain largely unexplored. In this study, we com...

science.org

biorxiv.org

Functional implications of polygenic risk for schizophrenia in human neurons - Nature Communications

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in ...

nature.com

Integrating perturbational screens, eQTL, and GWAS data identifies mediating genes for complex traits

Most current GWAS-eQTL approaches prioritize genes whose mediating effects on complex traits act through cis-regulation, while trans-acting genes remain largely underexplored. Recent perturbational sc...

medrxiv.org

The craniofacial shape of modern humans embodies genomic signatures of evolution, diversity, and clinical conditions

Human craniofacial morphology is a hallmark of our species' diversity and evolutionary history, shaped by adaptation, introgression, and global dispersal. Cranial globularization and chin emergence ar...

biorxiv.org

Causal modelling of gene effects from regulators to programs to traits - Nature

Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.

nature.com

doi.org

Genomics of drug target prioritization for complex diseases - Nature Reviews Genetics

In this Review, Chen et al. discuss how the advancement and integration of large-scale genetic resources, multi-omics data and sophisticated computational tools are improving drug development pipeline...

nature.com

Intraspecific sequence variation and complete genomes refine the identification of rapidly evolved regions in humans

Summary Humans exhibit significant phenotypic differences from other great apes, yet pinpointing the underlying genetic changes has been limited by incomplete reference genomes and a reliance on sing...

biorxiv.org

Simple scaling laws control the genetic architectures of human complex traits

Genome-wide association studies have revealed that the genetic architectures of complex traits vary widely. This study shows that differences in architectures of highly polygenic traits arise mainly f...

journals.plos.org

Nucleotide dependency analysis of genomic language models detects functional elements - Nature Genetics

Mapping pairwise nucleotide dependencies by leveraging genomic language models highlights functional genomic elements and predicts deleterious genetic variants more effectively than alignment-based co...

doi.org

Polygenic and developmental profiles of autism differ by age at diagnosis - Nature

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

nature.com

Multiancestry brain pQTL fine-mapping and integration with genome-wide association studies of 21 neurologic and psychiatric conditions - Nature Genetics

Multiancestry fine-mapping of brain protein quantitative trait loci coupled with Mendelian randomization analyses identifies protein–trait pairs consistent with causal effects across neurological and ...

nature.com

Machine Learning Models Based on Histological Images from Healthy Donors Identify ImageQTLs and Predict Chronological Age

Histological images offer a wealth of data. Mining these data holds significant potential for enhancing disease diagnosis and prognosis, though challenges remain, especially in non-cancer contexts. In...

biorxiv.org

Multiple overlapping binding sites determine transcription factor occupancy - Nature

A new method enables comprehensive screening and identification of low-affinity DNA binding sites for transcription factors, and reveals that nucleotides flanking high-affinity binding sites create ov...

nature.com

Genetic regulation of cell type–specific chromatin accessibility shapes immune function and disease risk

Understanding how genetic variation influences gene regulation at the single-cell level is crucial for elucidating the mechanisms underlying complex diseases. However, limited large-scale single-cell ...

medrxiv.org

Single-cell genetics identifies cell type-specific causal mechanisms in complex traits and diseases

Genome-wide association studies (GWAS) have been instrumental in uncovering the genetic basis of complex traits. When integrated with expression quantitative trait loci (eQTL) mapping, they can elucid...

medrxiv.org

Endogenous fine-mapping and prioritization of functional regulatory elements in complex genetic loci

Most genetic loci linked to polygenic traits are in non-coding regions, with complex regulation and linkage disequilibrium (LD), complicating causal v…

sciencedirect.com

The MUC19 gene: An evolutionary history of recurrent introgression and natural selection

We study the gene MUC19, for which some modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions. We find diagnostic variants ...

science.org

Polygenic prediction of human complex traits using ancient DNA

Ancient DNA has revolutionized our understanding of human history and clarified many aspects of human evolution on a molecular level. In this article,…

sciencedirect.com

The Importance of Regulatory Network Structure for Complex Trait Heritability and Evolution

Abstract. Complex traits are determined by many loci—mostly regulatory elements—that, through combinatorial interactions, can affect multiple traits. Such

academic.oup.com

Whole-genome sequencing of 490,640 UK Biobank participants - Nature

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation a...

nature.com

Regulatory network topology and the genetic architecture of gene expression

In human populations, most of the genetic variance in gene expression can be attributed to trans -acting expression quantitative trait loci (eQTLs) spread across the genome. However, in practice it is...

biorxiv.org

Single-cell eQTL mapping of human endogenous retroviruses reveals cell type-specific genetic regulation in autoimmune diseases - Nature Communications

Human endogenous retroviruses are abundant in the genome but poorly characterised. Here, the authors map their expression and genetic regulation in immune cells and identify disease-linked loci with p...

nature.com

Towards improved fine-mapping of candidate causal variants - Nature Reviews Genetics

Fine-mapping aims to distinguish between the causal and non-causal genetic variants identified in genome-wide association studies of complex traits. In this Review, Li and Zhou cover the recent method...

nature.com