Genes

Type 2 diabetes (T2D) affects 11.1% of the global population, underscoring the need for biomarkers that inform treatment response and glycemic outcomes. We evaluated the association between the FTO variant rs9939609-A and glycemic control in a Mexican population. A total of 174 individuals living with T2D from Merida and Sisal, Yucatan, were included, of whom 85% were receiving oral hypoglycemic agents as main treatment. Glycemic control was defined cross-sectionally as good ([≤]130 mg/dL, n=...

BackgroundKlebsiella pneumoniae is a common cause of neonatal sepsis in Africa, and is frequently hospital acquired. We recently reported an outbreak of multidrug-resistant K. pneumoniae sepsis amongst neonates at a rural hospital in The Gambia, West Africa, involving 57 cases and case fatality of 60%. Here we undertook a retrospective pathogen genomic epidemiology study of clinical and environmental K. pneumoniae isolated during the outbreak, to identify the outbreak strain, refine the epidemic...

MotivationFanconi anemia (FA) is a rare disease mainly caused by biallelic pathogenic variants, including structural variants such as large deletions and insertions in FA genes. Currently, variant detection is based on short-read sequencing and probe-based approaches. However, determining the exact genomic breakpoint or achieving allelic discrimination remains challenging. Nanopore-based long-read sequencing enables a comprehensive detection of FA variants, but a unified bioinformatic analysis p...

BackgroundColorectal carcinoma (CRC) remains a significant cause of cancer morbidity and mortality worldwide. Right- and left-sided tumours differ in clinical, morphological, and molecular features. Microsatellite instability-high (MSI-H) tumours, often right-sided, are associated with distinct histopathological characteristics and prognostic implications. In Sri Lanka, molecular MSI testing is currently unavailable, highlighting the need for alternative predictive approaches. ObjectivesGeneral...

Study question: How is glycodelin, a glycoprotein secreted by reproductive tissues, causally related to reproductive diseases and traits? Summary answer: We present evidence for a causal role of sex hormones in determining glycodelin levels, but limited evidence that glycodelin subsequently causally impacts reproductive traits. What is known already: Glycodelin is expressed in female and male reproductive tissues and has four glycoforms (-A, -C, -F and -S), with the glycosylation pattern determi...

BackgroundA coronary artery calcium (CAC) score of 0 is widely considered to indicate low short- to intermediate-term risk for coronary artery disease (CAD) and is frequently used to defer lipid-lowering therapy. However, a subset of individuals with CAC=0 still experience events, highlighting residual risk not captured by imaging alone. Polygenic risk scores (PRS) quantify lifelong inherited susceptibility, but conventional approaches rely on predefined ancestry labels despite human genetic div...

Accurate classification of BRCA1 and BRCA2 variants is essential for cancer risk assessment and therapy selection, yet over one-third remain variants of uncertain significance (VUS). Here, using 120,660 real-world cancer genomic profiles with BRCA1 or BRCA2 variants from a >800,000-sample cohort, we develop machine learning models that predict pathogenicity using clinical and tumor-derived features, including a pan-cancer homologous recombination deficiency signature, co-mutated genes, zygosity,...

Rare Mendelian disorders affect 300-400 million people globally. Although genetic testing has become widely adopted, gene-specific evidence for tailored variant interpretation remains scattered across resources. We present Gene Portals, a framework for gene-centered multimodal knowledge bases that co-localize expert-harmonized clinical data, functional assays, population variation, structural annotations and gene-specific ACMG/AMP specifications within a single resource. A modular interface inte...

Tumour typing from whole-genome sequencing is increasingly accurate, yet molecular subtyping from somatic variants remains challenging because of tumour heterogeneity and inconsistent clinical annotations. Here, we present Mutation-Attention Dual-Task (MuAt2), a Transformer model that jointly classifies histological tumour types and subtypes directly from somatic single-nucleotide variants, indels and structural variants. MuAt2 leverages encoders pre-trained on 2,587 pan-cancer whole genomes, an...

We report a previously undescribed genotypic configuration identified in twins with HNRNPU-related neurodevelopmental disorder. Both twins have two closely spaced mosaic variants on the same allele that never co-occur on any single DNA molecule, resulting in three distinct cell lineages within each individual. We define this genotypic configuration as clustered monoallelic mosaicism (cMoMa). Recognizing the extreme improbability of such a configuration, we systematically explore two potential me...

Chromosome 5p15.33 harbors several independent association signals which demonstrate antagonistic pleiotropy across cancer types, with causal mechanisms largely unresolved. To identify functional variants and enhancer elements at this locus, we performed statistical fine-mapping followed by massively parallel reporter assays (MPRA) and proliferation based CRISPRi screens. This approach identified eight multi-cancer functional variants (MCFVs) across three GWAS signals. Targeting rs421629 (part o...

BackgroundThe relationship between hip osteoarthritis (hip OA) and Alzheimers disease (AD) presents a critical paradox within the emerging "bone-brain axis": widespread phenotypic comorbidity sharply contradicts evolutionary theories of biological antagonism. This study integrates longitudinal and multi-omic analyses to determine whether this clinical overlap masks an underlying genetic neuroprotection. MethodsWe analyzed longitudinal phenotypic data from 261,767 UK Biobank participants using C...

Strengthening in-country sequencing capacity generated 28 Lassa virus genomes from human clinical cases, expanding our knowledge of Lassa fever in Guinea. Phylogeographic analysis revealed cross-border exchange between Liberia and the NZerekore region, and a Sierra Leone introduction into the Gueckedou area. Enhanced genomic surveillance is crucial to guide future public health actions.

Background: Quadriceps weakness may reduce sagittal plane shock absorption during landing, shifting load toward the frontal plane and increasing knee abduction moment (KAM), a biomechanical risk factor for anterior cruciate ligament (ACL) injuries. Purpose: The purpose of this study was to evaluate the association between isokinetic quadriceps strength and peak KAM during drop vertical jump landing in adolescent athletes. Study Design: Secondary analysis of previously collected data. Methods: He...

BackgroundEmerging research indicates that light exposure may influence sleep quality. Identifying key light-exposure behaviours associated with poor sleep quality in athletes may allow practitioners to efficiently screen for sleep difficulties and prioritise athletes for further assessment. Translating these findings into a practical screening tool could enhance willingness of high-performance professionals to monitor sleep and light exposure in athletes. HypothesisKey predictor variables iden...

Objectives: Compare Anterior Cruciate Ligament (ACL) Return to Sport after Injury (ACL-RSI) scores over time following ACL reconstruction (ACLR) between male and female patients aged 15 to 25 years with primary ACL injuries and ACL reinjuries. Design: Retrospective cohort design. Setting: Sports physical therapy clinics. Participants: 332 patients aged 15-25 years who underwent ACLR following either primary ACL injury or ACL reinjury, either contralateral or ipsilateral graft reinjury, and had a...

Background: Psychological readiness to return to sport and subjective knee function are critical outcomes following ACL reconstruction (ACLR), yet they do not always progress in parallel. An athlete may demonstrate high subjective knee function but low psychological readiness, suggesting a mental barrier to return, or conversely, report high readiness despite persistent functional limitations, raising concerns of overconfidence and reinjury risk. Understanding how these domains change together d...

This study compared the effects of a 25-min nap opportunity and a 10-min non-sleep deep rest (NSDR) condition on perceptual, cognitive, and physical performance in physically active young adults. Sixty participants (26 female, 34 male; 22 {+/-} 4 years) were randomly assigned to one of three groups (nap, NSDR, control; n = 20 each). All groups completed identical assessments immediately, 20 min, and 40 min post-intervention. Mixed-effects models, adjusted for sex, prior-night sleep, and weekly p...

Aim and ObjectivesThe study aimed to evaluate the effectiveness of titanium inserts for interdental papilla reconstruction, comparing it with the Han and Takei technique using subepithelial connective tissue grafts. The objectives included assessing the black triangle height, papilla height and papilla presence index (PPI) at baseline, 1 month and 3 months postoperatively along with the evaluation of Early Wound Healing Score (EHS) during the first week of post operative healing period. Patient...

IntroductionGenome-wide association studies (GWAS) for kidney function have mainly focused on creatinine-based glomerular filtration rate (eGFRcrea), which is affected by variation in muscle mass. Moreover, the genetic basis of the sexual dimorphism of chronic kidney disease is underexplored. MethodsWe performed a GWA meta-analysis for creatinine clearance (CrCl), a muscle mass-independent kidney function phenotype, in 58,976 individuals of European descent from the Lifelines Cohort Study. Res...