Psoriasis and rheumatoid arthritis (RA) are immune-mediated diseases that co-occur clinically, but their shared genetic architecture and the direction of shared effects remain debated. We integrated genome-wide association study (GWAS) summary statistics from FinnGen and UK Biobank using linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), ρ-HESS, MTAG, CPASSOC, colocalization, and MAGMA. The primary cross-population analysis showed a negative global genetic correlation (LDSC unconstrained: rg = − 0.3004, P = 6.70 × 10⁻³; constrained: rg = − 0.2251, P = 3.00 × 10⁻⁴; HDL: rg = − 0.3307, P = 1.14 × 10⁻³). Ancestry-matched sensitivity analyses produced positive but heterogeneous estimates (FinnGen: rg = 0.2422 to 0.6334; UK Biobank: rg = 0.1294 to 0.3777) that were not uniformly significant. Cross-trait analyses identified 95 independent SNPs and 10 additional shared loci. After allele harmonization, all 10 loci showed opposite MTAG effect directions for psoriasis and RA (two-sided exact binomial P = 1.95 × 10⁻³), indicating directional heterogeneity and possible antagonistic pleiotropy. Colocalization provided evidence for a shared causal signal at two TYK2 variants, rs11085727 and rs144309607 (PP.H4 > 0.8; r² = 0.0805 and D′ = 1.0), although these results should be interpreted cautiously because they may reflect distinct correlated variants. MAGMA identified immune-related tissue enrichment for psoriasis but not RA. Collectively, these findings indicate that psoriasis and RA share genetic loci, but the global direction of genetic correlation is ancestry- and data-source-dependent and that locus-level effects include opposing directions. TYK2 remains a plausible shared target, but its therapeutic implications require direction-aware fine-mapping and functional validation.
Childhood epilepsy, particularly when drug-resistant, often has an underlying genetic etiology. Populations with high consanguinity rates, such as Saudi Arabia, are expected to have a higher burden of autosomal recessive disorders. However, the diagnostic yield and clinical utility of whole-exome sequencing (WES) in this context require further characterization. We conducted a retrospective cross-sectional study at King Faisal Specialist Hospital and Research Centre-Jeddah (KFSHRC-J) between May 2017 and November 2021. We reviewed charts of all patients with clinical WES results (n = 561) and included 108 pediatric patients (< 14 years) for whom epilepsy was the primary indication for testing. Data on demographics, clinical presentation, radiological findings, and WES results were extracted from electronic medical records. Variants were classified according to ACMG guidelines. Among 108 patients (53 males, 49
Grain size and shape are important determinants of cereal yield and quality, yet their genetic regulation remains insufficiently characterized in rye (Secale cereale L.). Here, we examined associations of ScGDD1/BC12 transcript abundance and sequence variation with grain morphology in a panel of 91 winter rye genotypes comprising 78 gene bank accessions and 13 breeding materials. Relative transcript abundance was quantified at 14 days after pollination, and grain morphometric traits were evaluated in mature grains. Genome-wide DArTseq data available for 90 genotypes were used to assess population structure and as covariates in association models. Principal component analysis performed exclusively on grain phenotypic traits showed that Grain_PC1 explained 62.88
Antimicrobial resistance (AMR) is a major One Health challenge, yet wildlife remains underrepresented in surveillance systems. This systematized narrative review synthesized studies published between 2011 and 2025 on antimicrobial-resistant bacteria in bats, wild rodents, and marsupials, aiming to evaluate their role as reservoirs, disseminators, and ecosentinels of environmental AMR. The search was conducted in PubMed, SciELO, MEDLINE, and Scopus, and original studies reporting bacterial identification and phenotypic or genotypic resistance data were included. A total of 110 studies met the inclusion criteria, comprising rodents (n = 56), bats (n = 37), and marsupials (n = 17). The most frequently reported bacterial groups included Escherichia coli, Staphylococcus spp., Klebsiella pneumoniae, Enterococcus spp., and Salmonella spp. Rodents frequently harbored multidrug-resistant Enterobacterales, including ESBL-producing E. coli and resistance genes associated with last-line antimicrobials, reflecting exposure to urban, agricultural, and waste-contaminated environments. Bats were prominent reservoirs of resistant Staphylococcus spp., including methicillin-resistant strains, and carried clinically relevant Gram-negative bacteria, likely influenced by mobility, diet, colony behavior, and anthropogenic landscape exposure. Marsupials generally showed lower AMR burdens in free-ranging conditions, but captive and rehabilitated individuals exhibited increased resistance, suggesting human-mediated acquisition and amplification. Across host groups, the detection of mobile genetic elements and resistance determinants shared with clinical contexts supports the occurrence of cross-ecosystem exchange. These findings reinforce the need to integrate wildlife into AMR monitoring frameworks as early-warning indicators of environmental contamination and resistance dissemination.
The insulin receptor gene (INSR) encodes a ligand-activated tyrosine kinase that plays a central role in glucose homeostasis. Pathogenic variants in INSR are associated with a spectrum of insulin resistance syndromes. Here we report a novel INSR variant in a large multigenerational family. A 53-year-old woman presented to the endocrinology clinic with recurrent hypoglycemic episodes. Exome sequencing was performed for the index case, and variant segregation analysis was conducted in family members by Sanger sequencing. Genetic testing revealed a likely pathogenic variant in exon 19 of the INSR gene, NM_000208.4:c.3473G > C,p.(Arg1158Pro). Segregation analysis identified eight heterozygous carriers among thirteen tested family members. Reverse phenotyping revealed recurrent hyperinsulinemic hypoglycemia. Affected individuals demonstrated normal body mass index, low adiposity, and preserved fat-free mass, distinguishing this phenotype from classical insulin-resistance syndromes. Female carriers frequently exhibited hyperandrogenic features including hirsutism, menstrual irregularities, and acanthosis nigricans. These findings expand the clinical spectrum of INSR-related disorders and highlight the importance of considering INSR variants in patients with familial hyperinsulinemic hypoglycemia, particularly when clinical features mimic insulinoma.
