SEARCH · Search PubMed

Results for “genetic correlation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

562 records · Page 3Linked to original sources

PubMed2026

Diffusion MRI radiomics in meningiomas: imaging correlates of tumor grade and intraoperative consistency.

OBJECTIVE: Despite advancements in imaging studies, the preoperative prediction of the biological behavior and intraoperative consistency of intracranial meningiomas remains limited. This study evaluated the association of volumetric diffusion-based and texture-derived radiomic features extracted from routine MRI with histopathological aggressiveness and intraoperative tumor consistency. METHODS: Ninety-seven intracranial meningiomas resected at two tertiary centers were retrospectively analyzed. Volumetric segmentation was performed on contrast-enhanced T1-weighted MRI and coregistered to apparent diffusion coefficient (ADC) maps. Data on first-order diffusion metrics and selected texture features were collected. The associations between World Health Organization (WHO) grade and Ki-67 index were assessed using nonparametric tests and Spearman correlation analysis. Independent factors associated with intraoperative tumor consistency (Zada grades 1-5) were evaluated via multivariate ordinal logistic regression analysis that adjusted for tumor volume, skull base location, calcification status, and WHO grade. Secondary receiver operating characteristic (ROC) curve analyses were performed to differentiate solid (Zada grades 4-5) from soft (Zada grades 1-2) tumors. ROC analyses were performed within the study cohort and were intended as exploratory assessments of discriminative performance. RESULTS: The mean ADC (ADCmean) and the 10th percentile of the ADC decreased significantly with increasing WHO grade (p < 0.001). ADCmean had a moderate inverse correlation with the Ki-67 index (r = -0.42, p < 0.001) and intraoperative tumor consistency (r = -0.45, p < 0.001). In the multivariate analysis, the ADCmean remained independently associated with increasing tumor firmness. Each 0.1 × 10-3 mm2/sec increase corresponded to a 38% reduction in the odds of belonging to a higher consistency category (OR 0.62, 95% CI 0.51-0.74, p < 0.001). The ROC analysis showed good discrimination for solid tumors (area under the curve 0.847, 95% CI 0.742-0.953) and soft tumors (area under the curve 0.824, 95% CI 0.714-0.935). Texture features had weaker associations with intraoperative tumor consistency. CONCLUSIONS: Volumetric diffusion-derived metrics, particularly ADCmean, are associated with both histopathological aggressiveness and intraoperative tumor firmness in meningiomas. Diffusion imaging may reflect a graded microstructural continuum rather than a purely dichotomous property, providing complementary preoperative insights into surgical complexity.

Humans↗

PubMed2026

Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis.

CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.

Humans↗

PubMed2026

Metabolomics and genomics reveal high diversity and concentrations of cyanopeptides during a Microcystis bloom.

Cyanobacterial blooms are an immense global problem that release complex mixtures of poorly characterized biologically active cyanopeptides into freshwater. In this study, metabolomics and genomics were used to assess the diversity and concentrations of cyanopeptides during a dense Microcystis bloom during the late summer of 2023 in Lake Champlain, a large transboundary lake situated between Canada and the United States. Despite the relatively low genetic diversity of the bloom determined by 16S rRNA metabarcoding, 151 cyanopeptides were detected by non-targeted metabolomics. This represents the most recorded cyanopeptides from a single lake plankton bloom event to date. Fifty-two cyanopeptides were previously reported and 99 represent putative new structures. Standards from the microcystin, cyanopeptolin, microginin, and anabaenopeptin groups were used to either quantify or approximate respective cyanopeptide concentrations over the sampling period. Cyanopeptolins were the most diverse (n = 68) cyanopeptides and the second most abundant, reaching 12,892 μg/L. Microginins were the second most diverse (n = 24) and reached the highest concentrations (18,262 μg/L). Anabaenopeptins were the third most diverse (n = 17) cyanopeptides, reaching 4,818 μg/L. Only 8 microcystins were detected, reaching 4,935 μg/L, where MC-LR was the dominant congener. Target cyanopeptide biosynthesis genes for microcystins (mcyE), cyanopeptolins (mcnC), anabaenopeptins (apnD), microviridins (mdnC), and aeruginosins (aerA) were also quantified using digital droplet PCR (ddPCR). The gene copy numbers for mcyE, mcnC, and apnD were highly correlated with their corresponding cyanopeptide concentrations. Overall, the studied Microcystis bloom produced a very diverse cyanopeptide mixture with high cyanopeptide concentrations including non-microcystin groups.

Microcystis↗

PubMed2026

Electrocardiographic correlates of pacing induced cardiomyopathy and response to cardiac resynchronization therapy.

BACKGROUND: Chronic right ventricular (RV) pacing (RVP) causes pacing-induced cardiomyopathy (PICM) in only a small number of patients. We evaluated ECG correlates of (i) PICM and (ii) response to cardiac resynchronization therapy (CRT) upgrade. METHODS: We conducted a retrospective case-control study by including all CRT upgrades for PICM (LVEF <50%) at our center between 2014 and 2018. Controls were patients with ≥5 ECGs all demonstrating RVP over ≥2 years and all echocardiographic LVEF ≥50%. Root-summed-squared (3D) ECG was obtained from reconstructed vectorcardiographic X-Y-Z leads. Predictors of PICM and CRT response were assessed as area under ROC curve (AUC) for pre-CRT and Δ (post-CRT - pre-CRT) ECG intervals and QRS voltage-time-integrals (VTI). RESULTS: We included 104 patients with CRT upgrade for PICM (age 73.7 ± 10.5 years, female 29.1%, QRS duration 167.8 ± 25.2 ms, LVEF 28.8 ± 8.0%, ΔLVEF 13.8 ± 10.3%) and 178 controls without PICM (age 73.2 ± 14.9 years, female 52.8%, QRS duration 144.0 ± 20.9 ms, LVEF 56.7 ± 5.2%). PICM was best identified by VTIQRS-3D (AUC 0.851; VTIQRS-3D ≥ 80 μVs sensitivity 87.5%, specificity 63.5%), VTIQRS-Y (0.846), and QRS duration (0.775). CRT response (LVEF increase ≥10% at 3-12 months) occurred in 73/104 (70.2%) patients. Lack of CRT response was best predicted by longer pre-CRT QRS duration (AUC 0.640; QRS duration ≥180 ms sensitivity 45.2%, specificity 83.6%), and less ΔVTIQRS-3D (0.609) and ΔVTIQRS-X (0.608). CONCLUSION: In patients with chronic RVP, VTIQRS-3D ≥ 80 μVs can be used as a screening test for echocardiographic confirmation of PICM. RV-paced QRS duration >180 ms, on the other hand, identifies those who may not respond to CRT upgrade.

Humans↗

PubMed2026

Patterns and implications of co-use between vaping and hallucinogens: a systematic review and meta-analysis.

BACKGROUND: The co-occurrence use of e-cigarettes and hallucinogens has become increasingly common, particularly among youth and young adults. However, evidence regarding the association between these behaviors remains limited and fragmented. This systematic review and meta-analysis aimed to synthesize current evidence, examining the correlation between hallucinogen use and the likelihood of being an e-cigarette user. METHODS: A comprehensive search was conducted in PubMed, Scopus, Web of Science, EMBASE, and Cochrane CENTRAL up to June 2025. Eligible studies measured both hallucinogen and e-cigarette use and reported quantitative associations between these behaviors. Data extraction and risk-of-bias assessments were performed independently by three reviewers using the Newcastle-Ottawa Scale. Pooled effect sizes were calculated using a random-effects model (REML). Certainty of evidence was evaluated with the GRADE approach. RESULTS: Eleven studies met the inclusion criteria (n = 247,904), and seven were included in the meta-analysis (n = 217,478). The pooled analysis demonstrated that hallucinogen users had 4.47 times higher odds of being e-cigarette users (OR: 4.47, 95% CI 2.72 to 7.34; p < 0.001; I2 = 95.7%, n = 7). The certainty of evidence was rated as low. CONCLUSIONS: Hallucinogen use is directionally and strongly associated with e-cigarette use across diverse populations. Although the direction of association was consistent across studies, the magnitude of effect was heterogeneous. These behaviors likely share psychosocial and environmental determinants, although alternative explanations, including shared genetic liability, recall bias, and residual confounding, cannot be excluded. Further longitudinal studies are needed to clarify the underlying mechanisms of this association and establish temporality. The findings also support integrating hallucinogen-use screening into e-cigarette prevention and harm-reduction programs targeting youth and young adults.

Humans↗

PubMed2026

Genetic Diversity Analysis of Red Fox Populations (Vulpes vulpes L., 1758) in Natural and Anthropogenic Isolation.

This study presents a comparative analysis of the genetic structure and diversity of three red fox (Vulpes vulpes L.) populations representing different microevolutionary scenarios: panmixia (free-ranging Belarusian foxes), geographic isolation (free-ranging Scottish foxes), and anthropogenic selection (farm-bred foxes). Using a validated set of STR markers, multivariate statistical analysis was conducted to assess the genetic structure and the degree of genetic erosion across the studied groups. The wild red fox population in Belarus has been shown to maintain a state close to panmixia (PHWE = 0.090), characterized by a high effective population size (Ne = 694) and high allelic diversity. The island population from Scotland exhibits moderate gene pool depletion (Ne = 75.9) and a pronounced heterozygote deficiency (FIS = 0.18). Critical genetic erosion, which was characterized by a minimal effective population size (Ne = 60.2) and allelic fixation, was detected in the farm-bred group. The genetic distance between farm-bred and wild foxes (FST = 0.279; p = 0.001) reflects both the phylogeographic divergence between the Nearctic ancestors of farmed lineages and Palearctic wild populations, and the consequences of prolonged anthropogenic isolation, genetic drift, and selective breeding. These data indicate that artificial isolation and the impacts of genetic drift and targeted selection lead to a substantial depletion of the species' adaptive potential.

Animals↗

PubMed2026

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2 years) and the longer-lived cold-water Argopecten purpuratus (7-10 years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56 days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30 days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56 days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae↗

PubMed2026

Exploring the mechanism of aroma production in fermented cherry juice by L. brevis LD1.0600 using flavomics and whole genome analysis.

This study focused on L.brevis LD1.0600 with excellent fermentation traits: it analyzed genome-wide key regulatory genes for micro-metabolites, combined with fermented cherry juice flavor metabolomics data, and used machine learning to explore correlations between gene regulation, metabolite production, and flavor formation. The SVM model screened and verified fermented cherry juice VOCs; through OAV and flavor wheel analysis, LD1.0600 emerged as the top-performing strain, with a sweet, fruity dominant aroma. Key aroma-active components (OAV > 100) included 2-methoxy-4-vinylphenol, benzaldehyde, 2-methyl-butanoic acid and hexanoic acid, and 2-methoxy-4-vinylphenol and hexanoic acid elevated by LD1.0600-regulated genes (Chrom1-001884, Chrom1-000925, fabF and Chrom1-000199). At the same time, through research, a "strain screening-SVM screening of DVCs-OAV screening of key aroma components-whole genome sequencing of flavor regulatory genes" system was established. This system can not only be applied to the screen fermentation strains, but also can be extended to the application of other fermentation products.

Fermentation↗

PubMed2026

Alternative genetic codes in bacteria and archaea identified with a fast k-mer-based algorithm.

The genetic code is conserved across all domains of life and is often described as universal. Nevertheless, many exceptions to the "universal" code have now been documented, most of these through manual or semiautomated inspection of highly conserved genes. Modern bioinformatics tools improved our ability to find alternative genetic codes but remain computationally expensive, preventing widespread use on thousands of new species identified by sequencing environmental samples. Here, I report a >100-fold accelerated method for inferring the genetic code directly from assembled genomes and apply it to thousands of previously uncharacterized assemblies from archaea and bacteria. I describe three candidate genetic code variations, one of which, an alternative genetic code used by a family of Asgard archaea, is a unique example of sense codon reassignments for this domain. Identifying genetic code variations is important for understanding evolution of the standard code and improving accuracy of protein databases and open reading frame identification.

Genetic Code↗

PubMed2026

Characterizing 46,XY Differences of Sex Development: Novel Genetic Variants and Diagnostic Pitfalls in a Single-Center Cohort.

Explore the source record for details and available documents.

17β-hydroxysteroid dehydrogenase deficiency↗

PubMed2026

Changes in hemoglobin levels and cardiometabolic health in adults with metabolic syndrome - a secondary outcome analysis of a six-month randomized controlled trial.

BACKGROUND: Lower hemoglobin (Hb) levels within the normal range have been associated with favorable metabolic traits in cross-sectional studies. This study investigated whether changes in Hb levels correlated with changes in physiological and cardiometabolic parameters during a six-month behavioral intervention in individuals with metabolic syndrome. METHODS: The six-month randomized controlled trial aimed to reduce sedentary behavior in adults with metabolic syndrome (n = 64). Key measurements included fasting blood samples, insulin sensitivity during a hyperinsulinemic-euglycemic clamp, insulin-stimulated liver glucose uptake, liver fat content (LFC), indirect calorimetry, cardiorespiratory fitness, and cardiac function. Correlations between changes in these variables and changes in Hb levels at baseline, three, and six months were examined. RESULTS: Cross-sectionally, higher Hb levels correlated with lower insulin sensitivity (r=-0.35, p = 0.005), higher resting O2 consumption (r = 0.41, p < 0.001), higher resting energy expenditure (r = 0.49, p < 0.001), higher LFC (r = 0.40, p = 0.011), and greater left ventricular wall thickness (r = 0.42, p = 0.001). The intervention did not significantly impact Hb levels, and changes in Hb levels did not correlate with most cardiometabolic changes. However, reduced Hb levels correlated with reduced fasting blood glucose (r = 0.29, p = 0.032), improved insulin sensitivity (r = -0.26, p = 0.045), and increased cardiorespiratory fitness (r = -0.29, p = 0.033). CONCLUSIONS: Changes in Hb levels did not consistently correlate with changes in cardiometabolic markers during the intervention. However, reductions in Hb levels may relate to improved insulin sensitivity and fitness. Along cross-sectional correlations, this may be clinically relevant for individuals with metabolic syndrome. Further studies are merited to clarify the role of Hb levels in this high-risk group.

Humans↗

PubMed2026

The Animal Variant Classification Guidelines v2: An Update With New Criteria and Improved Clarifications.

The Animal Variant Classification Guidelines (AVCG) were developed to standardize and objectify the classification of putative disease-causing variants. These guidelines are sufficiently reproducible and are used to classify previously published and new disease-causing variants across species. Here, the guidelines are updated (AVCG.v2), based on a three-phase decision process. Overall, four new criteria and seven clarifying comments were added. The number of criteria has increased from 23 to 27, with three new criteria supporting pathogenicity and one new criterion supporting benign classification. Pharmacogenomic variants were determined to fall within the scope of the guidelines. These updated guidelines are being used by the Variant Pathogenicity Working Group (VPWG), part of the Animal Genetic Testing Standardization standing committee, which is a committee of elected members of the International Society for Animal Genetics (ISAG). Under the auspices of ISAG, the VPWG retrospectively classifies published putative disease-causing variants. The pathogenicity label for a variant will be presented in the variant tables of Online Mendelian Inheritance in Animals (OMIA; https://omia.org/). The AVCGv.2 criteria and recommendations were developed by the expertise of the animal genetics community and the ISAG Executive Committee through the Animal Genetics Testing Standardization Committee endorses and strongly encourages their use to evaluate the evidence supporting pathogenicity of putative disease-causing variants.

Animals↗

PubMed2026

Long-term (>7-year) parental consumption of genetically modified maize (Cry1Ab/Cry2Aj and EPSPS) induces no adverse sperm DNA methylation alterations across two generations of cynomolgus monkeys.

This study assessed the long-term safety of genetically modified (GM) maize from a male reproductive perspective, using a non-human primate model. We analyzed the sperm DNA methylation profiles in cynomolgus monkeys fed GM maize, non-GM parental maize, or a conventional diet over two generations (F0/F1). Whole-genome bisulfite sequencing (WGBS) revealed no significant differences in global methylation levels among groups. The identified differentially methylated regions (DMRs) were short, enriched in non-regulatory genomic areas, and did not cluster after treatment. Functional enrichment analysis showed that DMR-associated genes were consistently involved in the same core biological pathways (e.g., mTOR and Wnt signaling) across all dietary comparisons. These findings indicate that GM maize consumption did not induce specific adverse epigenetic alterations in sperm, with the observed changes reflecting common physiological adaptations to dietary variations rather than GM-related effects.

Animals↗

PubMed2026

Genetic overlap between estimated glomerular filtration rate and cardiovascular disease identifies potential targets for cardiorenal syndrome.

Heart and kidney diseases frequently coexist, but the genetic basis of this relationship remains unclear. We analyzed genetic data from large-scale studies to investigate how kidney function (estimated glomerular filtration rate, eGFR) and six common cardiovascular diseases share genetic risk factors. Using MiXeR method, and conjunctional false discovery rate (conjFDR) to identify overlapping genetic regions, we found 478 shared genomic loci between eGFR and cardiovascular diseases. These shared genes are involved in tissue development and structure. We also identified 29 genes that could be targeted by existing medications approved by the US Food and Drug Administration, such as PRKAG2, PDE1A, and IGF1R. Among these, genetically predicted higher level of IGF1R expression is associated with a higher eGFR, which reflects good kidney function and is protective against cardiorenal diseases, such as atrial fibrillation, and myocardial infarction. These findings reveal genetic overlap between kidney function and cardiovascular diseases, highlighting potential targets for understanding and treating cardiorenal syndrome.

Humans↗

PubMed2026

Genomics and molecular genetics in the post-genome-project era.

Explore the source record for details and available documents.

Editorial↗

PubMed2026

Unacknowledged Burdens and Clinical Assets of BIPOC Genetic Counseling Students: Qualitative Evidence to Inform Supervision.

As the genetic counseling profession works to diversify its predominantly white workforce, understanding the experiences of Black, Indigenous, and People of Color (BIPOC) students is central to equity efforts. While BIPOC students bring invaluable cultural and linguistic diversity that improves patient care, they often navigate clinical training environments that lack diversity and psychological safety. This article draws on data from a longitudinal constructivist qualitative study to examine how racial and ethnic concordance (or lack thereof) with patients and clinical supervisors influenced the clinical training, professional development, and well-being of BIPOC genetic counseling students. Semi-structured interviews were conducted with 25 BIPOC genetic counseling students in the United States and Canada. Interviews were recorded using Zoom.us, transcribed using Rev.com, and analyzed in NVivo using reflexive thematic analysis. The analysis led to the construction of three themes: (1)Shared identity with patients is a clinical advantage: Participants leveraged their cultural and linguistic intuition to establish trust and rapport with patients; (2) Identity navigation involves cognitive and emotional labor: Participants shouldered an unacknowledged burden in managing stereotype threat, overcoming feelings of exclusion, and educating supervisors; and (3) Racial/ethnic identity shapes supervisory dynamics: Participants described BIPOC supervisors as providing identity-affirming support, while some white supervisors avoided discussions about identity or committed microaggressions. These results suggest that BIPOC genetic counseling students have clinical assets rooted in biculturalism, yet carry a burden that often goes unacknowledged of managing power imbalances and pressure to assimilate in predominantly white clinical supervision spaces. To promote equitable training, programs should implement supervisor training on culturally responsive identity broaching, establish independent, transparent mechanisms for students to report biases they encounter in clinic, and expand mentorship networks to provide additional support.

Humans↗

PubMed2026

Are There Any Effective Behavior Change Strategies for Communicating Genetic Risk in Obesity Prevention and Body Weight Reduction Interventions?

This systematic review examined how differences in intervention components may contribute to inconsistent findings in genetic risk communication studies, addressing obesity-related outcomes (e.g., weight reduction, nutrition behavior, exercise). The review was preregistered (PROSPERO #CRD42024524026) and followed PRISMA guidelines. Searches across eight databases identified 23 randomized controlled trials, covering 18 intervention trials. Risk of bias was assessed using the Risk of Bias 2 tool. A narrative synthesis was used to cluster studies by the content of intervention and control groups. Genetic risk communication alone (no behavioral counseling, addressing nutrition and exercise) or combined with phenotype-based risk was ineffective and sometimes counterproductive among low-risk individuals. When combined with personalized behavioral counseling, effectiveness improved, but only when compared to waitlist control groups or non-personalized behavioral counseling. Significant effects emerged in high-genetic risk subgroups within personalized behavioral counseling, using behavior change techniques such as problem-solving, feedback on behavior, self-monitoring, and environmental changes. The most promising results emerged from complex interventions integrating genetic risk communication into multiple sessions and combining numerous additional behavioral change techniques, such as social reward, cues/prompts, self-reward. Complex personalized interventions combining multiple behavior change techniques and prompting experiential genetic risk awareness show promise for improving weight, nutrition, and exercise-related outcomes.

Humans↗

PubMed2026

Mapping the immune-genetic architecture of Epstein-Barr virus-related phenotypes and multiple sclerosis through a single-cell genetic framework for target prioritization and pharmacologic hypothesis generation.

BACKGROUND: Multiple sclerosis (MS) is a severe neuroinflammatory disease causing substantial long-term disability. Strong epidemiologic evidence links Epstein-Barr virus (EBV) exposure with MS risk, but genetic evidence for immune target prioritization in EBV-related phenotypes remains limited. METHODS: We integrated single-cell cis-eQTL data from 14 immune cell types with GWASs of an EBV-related clinical phenotype and MS using a single-cell Mendelian randomization framework with colocalization analyses. Candidate eGenes were evaluated in independent cohorts. For multi-SNP instruments, we performed heterogeneity, pleiotropy, MR-Egger, weighted median, mode-based, and MR-PRESSO sensitivity analyses. We also conducted phenome-wide association analyses and queried DrugBank to annotate candidate compounds targeting prioritized genes. RESULTS: We prioritized 43 immune-cell-specific candidate eGenes with convergent genetic support, including 6 for the EBV-related phenotype and 37 for MS. SERPINB1 in NK cells was associated with increased risk of the EBV-related phenotype, whereas HLA-G was associated with decreased risk. For MS, APOM and MSH5 showed protective associations, while AHI1 showed cell-type-dependent, bidirectional associations across immune lineages. Colocalization and independent cohort evaluation supported these findings. Among FDR-significant multi-SNP associations, MR-Egger intercept tests did not indicate directional pleiotropy, although a small subset showed heterogeneity or MR-PRESSO signals. Phenome-wide analyses identified no significant adverse phenotypic associations among evaluable genes at the prespecified threshold. DrugBank annotation nominated sodium nitroprusside, fasudil, artenimol, and choline as hypothesis-generating compounds for experimental follow-up. CONCLUSIONS: This study provides a single-cell genetic framework for prioritizing immune-cell-specific candidate targets for EBV-related phenotypes and MS, and nominates genetically supported targets and pharmacologic hypotheses for experimental investigation.

Humans↗