188 papers
This study identifies loss-of-function variants in the JAK1 gene as the underlying cause of epidermodysplasia verruciformis, revealing that impaired JAK1 signaling leads to defective interferon responses and T cell activation, thereby increasing susceptibility to cutaneous HPV infection and nonmelanoma skin cancer.
This epigenome-wide association study of discordant monozygotic and dizygotic twin pairs identifies differentially methylated regions, particularly at the CYP26A1 locus, implicating retinoic acid signaling and chromatin regulation in the etiology of nonsyndromic orofacial clefts while demonstrating the utility of twin designs in distinguishing environmental from genetic epigenetic contributions.
By integrating whole-genome sequencing with stomach-specific chromatin accessibility and promoter interaction analyses, this study identified novel oligogenic mechanisms involving deletions of regulatory elements in the CDH1 and MLH1 loci, as well as immune and mucin-related pathways, that explain the missing heritability in 47% of hereditary diffuse gastric cancer-like families.
This study demonstrates that an open-source Large Language Model pipeline, enhanced with retrieval-augmented generation on curated genetic corpora, can effectively analyze unstructured clinical notes to identify undiagnosed patients with rare genetic aortopathies who would benefit from genetic testing, achieving high accuracy and offering a promising decision-support tool for earlier disease recognition.
In a large-scale study of the All of Us Research Program, researchers found that social risk factors, such as perceived stress and adverse childhood experiences, exhibit stronger associations with bipolar disorder than genetic risk scores alone, demonstrating that integrating social and environmental data with genetics is essential for more accurate and equitable psychiatric risk prediction.
By analyzing 173 multiplex Portuguese families, this study reveals the shared genetic architecture of schizophrenia, mood disorders, and autism, identifying a rare CHD2 loss-of-function mutation that demonstrates how single neurodevelopmental gene disruptions can cross diagnostic boundaries to cause diverse serious mental illnesses.
This study reveals that while non-European patients with monogenic diabetes face a significant 70% annotation gap in ClinVar and gnomAD, the primary equity issue is not a simple excess of variants of uncertain significance but rather a distinct curation deficit and reclassification lag compared to European populations, highlighting the urgent need for ancestry-stratified evaluation of variant curation standards.
This study presents a proteogenomic analysis of 5,411 plasma proteins in 343 sickle cell disease patients, identifying 560 protein quantitative trait loci (including 58 novel ones) and using Mendelian randomization to prioritize five proteins that may increase fetal hemoglobin production as potential therapeutic targets.
A secondary analysis of a large U.S. survey reveals that attitudes toward mRNA vaccines are significantly shaped by religious affiliation, political orientation, and healthcare distrust, with Evangelical Protestants and those holding conservative or fundamentalist views showing greater skepticism compared to atheists and liberals.
This study identifies and corrects for key biases—such as population stratification, non-additive genetic effects, and mis-calibrated standard errors—in estimating the heritability of complex traits from ultra-rare variants, demonstrating significant contributions for specific phenotypes while highlighting the need for larger samples and improved methods for ordinal and binary traits.
This study identifies the non-coding variant rs4263114 at the 2p24.2 locus as the causal factor for non-syndromic cleft lip and palate, demonstrating that it increases disease susceptibility by disrupting FOXP2-mediated liquid-liquid phase separation, which impairs enhancer-promoter looping and suppresses MYCN expression in cranial neural crest cells.
Singapore's nationwide reproductive carrier screening program, utilizing a customized 112-gene panel tailored to Asian diversity, has successfully engaged thousands of couples and stakeholders since its 2024 pilot launch, demonstrating high community interest and religious support while highlighting the need for enhanced healthcare professional training and equitable outreach to address sociodemographic disparities in awareness and uptake.
This multi-ancestry study reveals that while kidney function and Alzheimer's disease lack a genome-wide genetic correlation, they share specific pleiotropic loci—most notably APOE across ancestries and others like PICALM and EFTUD1 in Europeans—where distinct causal variants and mixed horizontal and vertical pleiotropy explain the complex kidney-brain genetic axis.
This study analyzes the largest DNM1-related disorder cohort to date, revealing mutational hotspots, distinct genotype-phenotype correlations for recurrent variants, and a homogeneous clinical profile that supports the development of targeted therapies.
The paper introduces PAVS, a standardized, publicly accessible database integrating thousands of Saudi Arabian and global clinical cases with phenotype-genotype data to address the lack of population-specific resources and demonstrate high utility in prioritizing disease-causing genes for under-represented populations.
By analyzing over one million individuals, this study demonstrates that the disease risk associated with *TET2* and *DNMT3A* clonal hematopoiesis is driven by specific enzymatically disruptive mutations and can be accurately predicted using novel methylation-based activity scores that quantify functional impairment and outperform existing clinical risk models.
While integrating genetic testing into cardiology clinics significantly improved patient access and reduced wait times compared to traditional genetics referrals, it resulted in lower rates of informed decision-making, underscoring the critical need for structured education within mainstreamed pathways.
This paper reports the first case of a complex structural variant at the *FBRSL1* locus causing a profound developmental and epileptic encephalopathy, providing evidence for a dominant-negative mechanism and expanding the known phenotypic and genotypic spectrum of *FBRSL1*-related disorders.
Berrylyzer is an efficient, traceable, and lightweight AI-driven system that outperforms existing state-of-the-art tools in prioritizing causative variants for prenatal genetic diagnosis by effectively integrating both structured and free-text clinical data to achieve high accuracy and robustness across diverse diagnostic contexts.
RD-Embed is a lightweight, three-stage representation framework that unifies clinical text and coded signals to significantly improve rare-disease retrieval and diagnosis from heterogeneous electronic health records compared to existing models.