Mark J. Daly

Ultra-rare coding variants in schizophrenia risk genes are associated with longitudinal phenotypic differences across psychotic disorders

This study identifies ultra-rare damaging variants in schizophrenia risk genes and shows they are associated with earlier hospitalizations, greater childhood adversity, and poorer neuropsychological outcomes across psychotic disorders.

Sex-related signatures in the plasma proteome not attributable to XX and XY chromosomes and their impact on health and disease

The paper introduces the Proteomic Sex Index (PSI), a continuous measure of plasma proteome alignment with chromosomal sex, showing its association with health and disease traits.

Large language model classifies prior evidence in gene-phenotype associations

PESTO classifies gene-phenotype associations as Novel, Hypothesized, Existing, or Established using a large language model and structured genetic evidence, identifying 7% as Novel and 21% as Hypothesized in 940 associations.

Rare coding variation implicates thirteen genes in bipolar disorder across 232,536 individuals from global populations

Clinical history shapes the predictive value of polygenic risk

The paper develops and validates polygenic risk scores (PRS) for 150 diseases and mortality using UK Biobank and FinnGen data, showing genetic information provides the largest predictive gains for certain diseases but not others.

Autism genes converge on three functional programs organized by neuronal subclass, developmental timing, and cortical patterning

This study identifies three functional programs impacted by autism genes, contextualized across neuronal subclasses, developmental timing, and cortical regions.

Scalable context-dependent single-cell eQTL mapping reveals disease-relevant regulatory variation beyond static models

The paper introduces CASTIE, a method for context-dependent eQTL mapping in single-cell data, identifying regulatory variants missed by static models and linking them to disease traits.

Rare variation illuminates the distinct and pleiotropic genetic architecture of autism across neuropsychiatric traits

The paper identifies 253 autism-associated genes using rare variation from 62,429 individuals and finds pleiotropy across physiological systems and developmental disorders.

A unified framework for local-ancestry-aware genetic association analysis across biobanks

FELIX improves genetic association analysis by accounting for local ancestry in admixed populations, increasing significant loci and improving polygenic score prediction.

Systematic identification of disease-associated 3D neighborhoods in protein structures

The paper develops a framework to map rare variants onto protein structures and identifies disease-associated 3D neighborhoods in 872 genes for Mendelian disease and others for autism, epilepsy, and schizophrenia.

Resolving inflammatory bowel disease risk variants to genes and cell types

This study identifies 619 IBD risk signals, resolves 81 high-confidence variants, and prioritizes 664 candidate effector genes using GWAS, eQTL, and exome sequencing.

Genetic variants affect diurnal glucose levels throughout the day

The paper identifies genetic variants associated with diurnal glucose levels and their role in type 2 diabetes risk.

Exome sequencing directly implicates 68 genes in inflammatory bowel disease

This study uses exome and genome sequencing to identify 68 genes directly associated with inflammatory bowel disease, providing clearer genetic insights and therapeutic targets.

Systematic common and rare variant association testing in 392,030 whole genomes in All of Us

The paper performs large-scale GWAS and RVAS on 392,030 whole genomes from All of Us, identifying 49,863 associations and 193 novel pLoF gene-phenotype links through meta-analysis with UK Biobank.

Modeling rare coding variation on chromosome X provides insight into the genetics and differential sex prevalence of autism spectrum disorder

The paper develops a model to analyze X-linked rare variation in ASD, identifying 9 genes associated with ASD and explaining how X-linked variation could contribute to sex-differential prevalence.

Integrating 730,947 exome sequences with clinical literature improves gene discovery

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

Gene Portals: A Framework for Integrating Clinical, Functional, and Structural Evidence into Rare Disease Variant Classification

The paper introduces Gene Portals, a framework that integrates clinical, functional, and structural data for rare disease variant classification, demonstrating its utility across five gene-specific portals.

Characterization of the functional and clinical impacts of CACNA1A missense variants found in neurodevelopmental disorders

This study analyzes 42 de novo CACNA1A missense variants in neurodevelopmental disorders, finding most alter channel function and correlate with clinical outcomes.

Cystic fibrosis risk variants confer protection against inflammatory bowel disease

The paper identifies CFTR loss-of-function variants as protective against IBD using large-scale exome sequencing data and evaluates variant prioritization methods.

Population-scale multiome immune cell atlas reveals complex disease drivers

The paper uses population-scale single-nucleus ATAC-seq and RNA-seq to identify regulatory variants and their disease associations in immune cells.

The 9p21.3 Coronary Artery Disease Risk Locus Modulates Vascular Cell-State Transitions via Enhancer-Driven Regulation of MTAP

This study identifies 12 enhancers in the 9p21.3 CAD risk locus that regulate MTAP, modulating vascular cell-state transitions and CAD risk through stress-responsive mechanisms.

Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

Industrialization drives convergent microbial and physiological shifts in the human metaorganism

The paper investigates how industrialization affects microbial and physiological traits in the human gut across diverse populations, finding homogenized microbiomes, reduced diversity, and impaired disease prediction accuracy in less industrialized groups.

Improved Allele Frequencies in gnomAD through Local Ancestry Inference

This paper improves allele frequency estimates in gnomAD by applying local ancestry inference to admixed populations, revealing significant frequency differences that could affect clinical interpretation.

Blood donor biobank pipeline to collect genome-based samples for research

The paper describes a pipeline for collecting high-quality blood samples from donors for multi-omics research, demonstrating their suitability for genetic and phenotypic studies.

Genetic and structural evidence links calcium dysregulation and ATP2B2 to neuropsychiatric illness

The paper integrates genetic, transcriptomic, and structural data to show that Ca2+ dysregulation via ATP2B2 missense variants contributes to neuropsychiatric disorders.

Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty

This study identifies 1,242 novel genetic variants and 31 novel genes associated with frailty through genome-wide association and proteomics integration.

Frequency enrichment of coding variants in a French-Canadian founder population and its implication for inflammatory bowel diseases

The paper identifies enriched coding variants in a French-Canadian founder population and explores their association with inflammatory bowel diseases.

Genome-wide Association Study Identifies SORCS3 as a Novel Susceptibility Locus for Panic Disorder in the FinnGen Study

This paper identifies SORCS3 as a novel genetic locus associated with panic disorder through a genome-wide association study in the FinnGen study and validates it in independent samples.

PGS Browser: a public platform for personalized polygenic score interpretation

The paper benchmarks polygenic scores in a large cohort, identifies top-performing models, and provides a public platform for PGS analysis and interpretation.