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...

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...

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 ...

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...

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...

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

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...

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...

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...

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

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.

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 ...

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...

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...

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 ...

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...

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

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 ...

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

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

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...

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...

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...

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...

Author summary Obesity is linked to many chronic diseases and its prevalence worldwide is increasing. Susceptibility to obesity is known to be due, to some degree, to genetic factors, and such genetic...

Here, the authors present trained models of genetically regulated enhancer RNA expression, finding that genetically regulated expression predicts chromatin contact frequency and that enhancer RNAs pla...

Most variants identified from genome-wide association studies (GWASs) are non-coding and regulate gene expression. However, many risk loci fail to col…

This mass spectrometry-based proteomic study profiles the plasma proteome in 2,147 children and adolescents and reveals its association with age, sex, puberty, body mass index and genetics.

Whole genome sequencing has identified over a billion non-coding variants in humans, while GWAS has revealed the non-coding genome as a significant contributor to disease. However, prioritizing causal...

European Journal of Human Genetics - Looking back at 2024 in the European Journal of Human Genetics

Genetic association studies provide a unique tool for identifying causal links from genes to human traits and diseases. However, it is challenging to determine the biological mechanisms underlying mos...

FLAMES is a machine learning approach combining variant fine-mapping, SNP-to-gene annotations and convergence-based gene prioritization scores to identify candidate effector genes at genome-wide assoc...

Mapping transcription start sites across five mammalian species before, during, and after embryonic genome activation unveils widespread transposable element-driven transcription and co-option of evol...

The authors explore how short tandem repeats in DNA sequences affect risk of Alzheimer’s disease. They find that individuals who carry a high burden of expanded repeats in their DNA have a more than t...

Mapping of multi-omic molecular quantitative trait loci associated with tandem repeat size variation in up to 4,412 human brain samples from 1,597 donors offers insights into how these variants affect...

Analysis of single nuclei RNA-sequencing data across eight major brain cell types identifies putative causal associations between cell-type-specific expression and brain phenotypes.

Tripotential intermediate progenitor cells are responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells and astrocytes in the human neocortex.

Popp et al. generate dozens of cell types from 53 human iPSC lines in order to characterize the dynamic genetic regulation of gene expression across early stages of cellular differentiation. Accessing these understudied contexts can clarify the functional impact of disease loci with unknown mechanisms of action.

Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by anal...

Nature - Earliest modern human genomes constrain timing of Neanderthal admixture

Gene flow from Neanderthals has shaped genetic and phenotypic variation in modern humans. We generated a catalog of Neanderthal ancestry segments in more than 300 genomes spanning the past 50,000 year...