189 papers
This study demonstrates that Nanopore long-read sequencing combined with targeted de novo assembly provides a highly accurate, reference-free method for resolving the complex human opsin gene cluster, enabling precise diagnosis of color vision deficiencies and reliable carrier detection where current alignment-based methods fail.
TumorLens is a unified long-read sequencing framework that simultaneously detects diverse genetic and epigenetic alterations, including SNVs, structural variants, copy-number changes, and methylation patterns, to enable comprehensive tumor profiling and advance precision oncology.
This study of over 500,000 veterans demonstrates that the externalizing spectrum, characterized by behavioral disinhibition and shared genetic factors, is a significant and often overlooked predictor of suicide-related outcomes, including ideation, attempts, and death.
This study introduces a new statistical framework demonstrating that local ancestry significantly modulates gene expression through ancestry-specific regulatory variants, thereby explaining cross-population inconsistencies in genomic studies and improving the understanding of disease risk and health disparities in Hispanic/Latino and African American populations.
This meta-analysis of over 190,000 individuals demonstrates that the GBA1 p.E427K variant is a significant risk factor for synucleinopathies, including Parkinson's disease, with an effect size comparable to established risk variants and supported by reduced glucocerebrosidase enzymatic activity.
This study utilizes a multi-ancestry trio-based whole-genome sequencing approach to identify four genome-wide significant loci, including novel subtype-specific associations for alveolar involvement and left-sidedness, thereby demonstrating the value of granular phenotypic characterization in uncovering distinct genetic etiologies within isolated cleft lip.
This study utilizes clustered Mendelian randomization to reveal that major depressive disorder comprises distinct genetic subtypes with opposing causal effects on type 2 diabetes and cardiometabolic health, where one cluster linked to atypical symptoms increases metabolic risk while another linked to melancholic symptoms decreases it.
By integrating long-read sequencing, epigenetic profiling, and imputation strategies across hundreds of individuals, this study characterizes the complex haplotype and structural variant landscape of Alzheimer's disease GWAS loci, identifying numerous candidate structural variants that likely drive disease mechanisms through regulatory and epigenetic alterations.
The paper introduces CoNVict, a two-stage agentic AI system that leverages large language models to automate the prioritization of copy number variants in rare disease diagnosis by integrating patient phenotypes and performing pairwise comparisons, thereby outperforming existing tools in identifying causal variants while bridging the gap between automated annotation and clinical reasoning.
This study utilizes proteome-wide Mendelian randomization to identify 18 causal proteins for bone mineral density and fracture risk, with a specific focus on establishing tissue inhibitor of metalloproteinases 2 (TIMP2) as a promising new therapeutic target due to its genetically supported association with lower bone density and increased fracture risk.
This study conducted a genome-wide association meta-analysis of over one million individuals to identify 54 genetic loci associated with urinary incontinence and its subtypes, revealing distinct tissue-specific mechanisms and confirming causal risk factors such as smoking, BMI, and pelvic organ prolapse.
By integrating signatures of recent positive selection with cross-trait genetic association data across 13 South Asian populations, this study identifies IP6K3 and MAPT as metabolically relevant loci for type 2 diabetes and establishes a scalable framework for genomic discovery in underrepresented groups without relying on ancestry-matched molecular resources.
By integrating multi-trait GWAS, gene-based testing, and functional annotations, this study significantly expands the genetic landscape of spontaneous coronary artery dissection (SCAD) by identifying 40 independent loci and 56 candidate genes that implicate arterial wall integrity, extracellular matrix organization, and TGF-beta signaling as key biological mechanisms.
This study found that while both AI predictions and explainable AI (XAI) saliency maps improved diagnostic accuracy when the AI was correct, medical geneticists relied more heavily on the raw prediction probabilities than on XAI explanations, which were viewed less favorably and failed to significantly enhance decision-making integration.
This multi-ancestry genome-wide association study meta-analysis of over 54 cohorts identifies 77 significant genetic loci for suicidality, revealing novel biological insights into synaptic pathways and subcortical neuronal populations while establishing suicidality as a polygenic trait with both shared and distinct genetic influences.
Using long-read sequencing, this study reveals that three CAA interruptions within intermediate ATXN2 CAG repeats are rare in healthy controls but highly prevalent in ALS patients, where they are strongly associated with a specific European haplotype tagged by the SNV rs148019457, offering a potential marker for precision genomic medicine.
By employing a novel multi-level trivariate genetic analysis framework, this study identifies that 55% of the genetic risk for insomnia, depression, and anxiety is shared, converging on synaptic processes and highlighting specific druggable genes like CACNA2D3, DRD2, GRIA1, and GRM5 as promising transdiagnostic therapeutic targets.
This study utilizes sex-stratified genome-wide association analyses to reveal that while the overall genetic architecture of alcohol use is largely shared between sexes, distinct genetic loci, correlations with comorbid traits, and medical outcomes exist, highlighting the importance of sex-aware approaches in understanding the genetic etiology of alcohol use behaviors.
This multicenter study of 30 patients provides the first radiological description of the natural history of PIK3CA-related overgrowth spectrum (PROS), demonstrating that tissue malformations typically exhibit sustained progression and volume increase into adulthood.
This study found no association between ZFHX3 GGC repeat expansions and amyotrophic lateral sclerosis (ALS) risk, but revealed a highly diverse landscape of repeat motif compositions, including pure polyglycine tracts, suggesting that motif configuration alongside allele length is crucial for understanding neurodegenerative disease mechanisms.