Exposure to lung irritants such as smoking and organic solvents has been associated with increased risk of multiple sclerosis (MS), particularly among genetically susceptible individuals. The aim of this study was to investigate the association between occupational exposure to industrial dust and MS and to assess potential interactions with smoking and HLA-DRB1*15:01. We conducted a Swedish population-based case-control study. Patients with incident MS age 16-70 years were consecutively identified by neurologists at 40 clinics (2005-2015). Eligibility criteria for participants were age 16-70 years, residence in Sweden, and a neurologist-confirmed diagnosis of MS according to the McDonald criteria. Controls without MS were randomly sampled from the national population register using density sampling and frequency-matched to cases on age, sex, and residential area. Occupational dust exposure was assessed using questionnaire data. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Additive interactions between dust exposure and smoking and between dust exposure and HLA-DRB1*15:01 were assessed by calculating the attributable proportion (AP) due to interaction. An AP >0 is considered evidence of interaction. The analytic sample included 2,070 participants and 2,899 controls. The mean age at index was 34.4 years for participants and 35.4 years for controls. Women comprised 72.5% of participants and 75.1% of controls. Industrial dust exposure was associated with increased rate of MS (OR 1.30, 95% CI 1.05-1.63), with a dose-response relationship with duration (OR per 1-year exposure 1.03, 95% CI 1.00-1.06). Evidence of additive interactions was observed between dust exposure and smoking (AP 0.32, 95% CI 0.03-0.62) and between dust exposure and HLA-DRB1*15:01 (AP 0.25, 95% CI 0.002-0.52). Participants who smoked, were exposed to dust, and carried the HLA-DRB1*15:01 allele had an 11-fold increased rate of MS (OR 11.1, 95% CI 5.7-21.9), compared with those without any of these risk factors. Occupational dust exposure was associated with increased rate of MS, particularly in combination with smoking and HLA-DRB1*15:01, suggesting joint effects of occupational, environmental, and genetic risk factors. The reliance on self-reported occupational histories and potential residual confounding are important limitations. Further studies are warranted to clarify underlying mechanisms and to inform preventive strategies.

Polygenic risk scores for pediatric obsessive-compulsive symptoms: Mediating effects in samples clinically diagnosed with mental disorders.

Late-onset Alzheimer's disease (AD) arises in part from a complex genetic architecture dominated by common, low-penetrance variants, many of which are enriched in glial cells and remain mechanistically unresolved. Unlike the rare coding mutations that contribute to early-onset AD, these common variants often lie in noncoding regions, complicating efforts to link genetic risk to cellular function. Emerging evidence suggests that many glial-enriched risk genes contribute to disease by disrupting communication between glia and neurons. Such interactions are essential for preserving synaptic health and modulating immune responses to pathology. Understanding how polygenic variation perturbs these pathways requires integrative strategies that combine large-scale postmortem brain datasets with experimentally tractable human cellular models. In this review, we highlight recent progress in decoding the cellular impact of AD risk variants through the lens of glial-neuronal communication. We first illustrate how human brain studies have mapped cell-type-specific gene expression and intercellular networks associated with genetic risk. We then discuss how human stem cell-derived co-culture and 3D models are being used to test these hypotheses in controlled experimental systems. As a case study, we focus on CLU (Clusterin), a well-replicated risk locus that modulates glial inflammation, lipid exchange, and neuronal vulnerability. Together, these studies build a scalable, human-centric framework for linking genotype to function and point toward new opportunities for therapeutic discovery rooted in intercellular biology.

Mapping modifiable risk factors for incident epilepsy: a large prospective cohort study.

Type 1 diabetes (T1D) exhibits sex differences in genetic risk, yet most genetic studies treat sex as a covariate rather than a modifier of risk. We hypothesized that sex-stratified genome-wide association studies (GWAS) would uncover sex-specific genetic architecture and improve risk prediction. We performed GWAS in 6,599 T1D cases (3,483 males, 3,109 females, 7 undetermined) and 12,350 controls (6,665 males, 5,658 females, 27 undetermined) of European ancestry, testing additive models and sex-stratified analyses. For mechanistic insights, we performed scRNA-seq of PBMCs from nine matched male-female pediatric pairs. Finally, we tested male-, female-, and standard polygenic risk scores (PRS) in an independent cohort (471 T1D cases, 2,300 controls). Sex-stratified analyses identified 215 genome wide significant SNPs (P<5x10-8) with heterogeneity: 119 male-specific and 94 female-specific. Integration of scRNA-seq data revealed 41 sex-specific T1D genes with cell type-specific differential expression. In the independent cohort, sex-specific PRS outperformed the combined PRS: in males, AUC=0.668 versus 0.623 (p<2.2x10-16); in females, AUC=0.719 versus 0.635 (p<2.2x10-16). Sex-stratified GWAS reveal novel T1D risk loci influenced by sex. Incorporating sex-specific effect sizes into PRS enhances risk discrimination, underscoring the value of sex-aware genetic analyses for precise prediction of T1D.

Marked comorbidity between mental disorders and immune-mediated inflammatory diseases (IMIDs) suggests a bidirectional interplay, yet most prior work has tackled a single analytic direction, leaving the overall structure of time-ordered associations unclear. Using the large, longitudinal UK Biobank cohort, we fitted Cox proportional-hazards models to quantify bidirectional, time-ordered associations between eight prototypical mental disorders and eight common IMIDs. Genetic susceptibility was quantified with polygenic risk scores (PRSs), and mediation models incorporated systemic inflammatory markers and sleep-quality scores. Baseline mental disorders significantly increased IMID incidence (comorbid mental disorders [CMB]→IMIDs: HR=1.84, 95% CI 1.70-1.99). Major depressive disorder showed the widest range of associations, while post-traumatic stress disorder exhibited the strongest single link, notably with sicca syndrome (HR=5.88, 95% CI 1.47-23.6). Conversely, baseline IMIDs heightened subsequent mental-disorder risk (IMID → CMB: HR=1.54, 95% CI 1.45-1.63). In PRS-stratified analyses, psychiatric disorders (exposure) were more strongly associated with later IMID risk (outcome) in participants with lower versus higher genetic IMID risk. In PRS-based effect-modification analyses, we observed super-additive interaction on the additive scale for several pairs. Mediation analyses suggested that systemic inflammation and sleep disturbance accounted for roughly 2-10% and 7-16% of the associations, respectively. This systematic, bidirectional framework maps a complex interaction network linking IMIDs and mental disorders, jointly mediated by genetic vulnerability, systemic inflammation, and sleep dysregulation. The findings furnish a psychoneuroimmunological basis for integrated preventive and therapeutic strategies.

Chronic stress, gut dysbiosis, and cholesterol metabolism: Implications for Alzheimer's disease.

Anhedonia is an important symptom in major mental disorders and is difficult to address due to a limited understanding of its neurobiological and genetic underpinnings. Here, we investigated the effect of a polygenic risk score (PRS) for anhedonia on brain activation during a well-established monetary incentive delay (MID) task, while performing functional magnetic resonance imaging. We derived an anhedonia PRS from a large genome wide analysis (n=375,275) in our sample of 517 subjects. This sample consisted of four subgroups (healthy controls (n=373), major depressive disorder (n=57), schizophrenia (n=39) and bipolar disorder (n=48)). We tested for correlation between the individual PRS and brain activation during reward and during loss anticipation and feedback. Additionally, we analysed the correlation between PRS and structural volume size of three reward-related brain areas as well as between PRS and anhedonia scores. We showed that increased PRS was associated with decreased activation in bilateral putamen and left middle frontal gyrus during anticipation and decreased activation in the right caudate during feedback across all subgroups. Moreover, a higher PRS was also correlated with lower activation in left middle frontal gyrus during loss anticipation and salience processing. During loss feedback, higher PRS was correlated with hyperactivity of bilateral putamen and right caudate. No significant correlation was found between PRS and brain volume or anhedonia scores. Our results highlight the importance of the striatum and prefrontal cortex in the context of a genetic risk for anhedonia.

Advancing substance use disorder biology by studying underlying gene x environment interactions.

Psoriasis (PsO) demonstrates frequent co-occurrence with metabolic syndrome (MetS). Nevertheless, the shared genetic architecture underlying both pathological conditions remains incompletely characterized. This investigation sought to examine genetic correlations between PsO and multiple MetS-associated traits, and to identify shared genetic risk loci and genes contributing to their coexistence. Genome-wide association study data for PsO, MetS, and related traits in European populations were integrated to evaluate genetic associations between traits and to identify shared loci. Bayesian colocalization analysis was applied to determine whether association signals for different traits at the same locus were attributable to a common causal variant. Functional annotation and gene mapping were conducted for shared loci, followed by functional classification and pathway enrichment analyses of pleiotropic gene sets. In addition, summary data-based Mendelian randomization and transcriptome-wide association study analyses were applied to prioritize candidate genes with potential therapeutic relevance. Significant genetic associations were observed between PsO and five metabolic traits, including body mass index, high-density lipoprotein cholesterol, triglycerides, waist circumference, and type 2 diabetes mellitus, while MetS, as a composite trait, also exhibited a genetic association with PsO. Pleiotropic Analysis under composite null hypothesis (PLACO) analysis revealed a total of 141 shared risk loci, with 22 loci substantiated by Bayesian colocalization analysis findings (PP.H4 ≥ 0.75). Multimarker analysis of genomic annotation analysis identified 195 distinct pleiotropic genes. The pathway enrichment analysis indicated that these genes were predominantly involved in immune and inflammatory pathways, transcriptional and epigenetic regulation, autophagy, and lipid-cholesterol metabolism, indicating that such biological processes may contribute to the shared genetic background of PsO and MetS-related traits. Through integrative evidence from multiple analytical approaches, three candidate therapeutic target genes, namely, KAT8, STX4, and VKORC1, were prioritized. Shared genetic loci, pleiotropic genes, and core biological pathways between PsO and multiple MetS-related traits were identified, and potential intervention targets were highlighted, providing genetic evidence to support subsequent functional investigations.

BackgroundHabitual daytime napping is a significant aspect of many older adults' sleep-wake cycle. Growing evidence links napping and cognition in the context of Alzheimer's disease (AD), yet little is known about how genetic risk influences this relationship.ObjectiveThis study investigates interactions between genetic risk for AD and napping on cognition in 1655 cognitively healthy middle-aged to older adults.MethodsCognition was assessed using a self-administered online battery and reduced to three variables: memory, visuospatial abilities and executive functions. Genetic risk was assessed with the presence of APOE ɛ4 allele and polygenic risk scores for AD (PRS; excluding APOE). ANCOVA assessed interactions.ResultsThere was a significant interaction between APOE ɛ4 and napping duration on the memory component (F(2,1645) = 3.84, p = 0.022, ηp2 = 0.005). APOE ɛ4 carriers reporting long naps demonstrated better memory than non-carriers also reporting long naps. Among APOE ɛ4 carriers, those who napped for ≥ 1 h performed better than those reporting shorter naps. In a separate analysis, there was a significant interaction between PRS and napping (F(2653) = 3.44, p = 0.033, ηp2 = 0.010). Low PRS was related to better memory than high PRS among those who did not nap. Within the low PRS group, participants who did not nap outperformed those reporting short naps. Results remained significant after accounting for overnight sleep efficiency.ConclusionsFindings suggest that the relationship between napping and memory may vary as a function of genetic risk for AD. Results could inform studies looking into personalized preventative treatment based on genetic profiles.

Both genetic and environmental factors affect human stature, including overall height and familial short stature (FSS), and it is associated with various health outcomes. However, the study of genetic connections between stature and health conditions remains lacking in East Asian populations. Hence, we conducted parallel genome-wide association studies (GWAS) of body height and FSS in the Han Taiwanese population, aiming to elucidate the genetic influences of stature on health and facilitate the formulation of precision-health strategies. We analyzed large-scale GWAS data on adult height (120,301 Han Taiwanese) and FSS (FSS; 2,050 cases, 27,966 controls) to examine cross-trait genetic correlations across five East Asian biobanks, and applied phenome-wide association studies (PheWAS) and polygenic risk score (PRS) analyses to assess clinical outcomes using Cox proportional hazard models and Kaplan-Meier analyses. We identified 293 loci for height and five for FSS, with cross-biobank genetic correlations linking stature to body size, lung function, and cardiovascular/reproductive traits (atrial flutter/fibrillation [AF], menarche, and endometriosis). PheWAS showed that height PRS increased risks of AF and endometriosis, while FSS PRS had a protective effect against endometriosis. MR analyses showed that taller stature increased AF risk independently and endometriosis risk through menarche/weight, while shorter stature had a weak protective effect against endometriosis. Survival analyses showed the association of higher height PRS with greater AF risk and an earlier divergence of cumulative incidence curves. These time-to-event patterns were consistently replicated using meta-analysis-derived PRSs. The findings highlight stature-related genetic determinants, associated health outcomes, and polygenic risk scores as effective tools for early risk prediction and precision health strategies in East Asian populations.

In the present study, the novel family genetic risk score (FGRS) method, a reliable quantification of latent genetic risk, was applied to posttraumatic stress disorder (PTSD) to examine associations between genetic liability and clinical features of PTSD among 3,097,180 individuals in the Swedish national registries. FGRS was calculated based on lifetime PTSD status for first- through fifth-degree relatives and examined both in PTSD cases with any lifetime registration (PTSD total) and in cases with more than one registration (recurrent PTSD) in relation to sex, age at onset (AAO), recurrence, mode of ascertainment (inpatient [IP], outpatient specialty care [SC], primary care [PC]), and comorbidities. Sex differences were not found for recurrent PTSD, but for PTSD total, female registrants had a lower FGRS value compared to male registrants, M = -.017, 95% CI of difference [-.029-.005]. Higher FGRS was found at earlier AAO for PTSD total and recurrent PTSD, ps <.001, and scores were higher among individuals with comorbidities, ps <.001. Higher FGRS was related to the number of PTSD recurrences among both total PTSD and recurrent PTSD, ps <.001 (linear effect). For both PTSD types, FGRS scores were as follows: PC < SC < IP, ps <.001. The findings indicate that genetic risk for PTSD is associated with several clinical features of the disorder, which should be included in future studies of genetic risk for PTSD. Continued investigation of these clinical features in epidemiological and molecular genetic studies of PTSD is warranted to further validate the findings.

Cancer survivors are at elevated risk of developing subsequent cancers. Solid organ transplant (SOT) recipients also have elevated cancer risk, but the pattern of subsequent cancer risk among SOT recipients with a pretransplant cancer has not been studied. To assess the association of pretransplant cancers with posttransplant cancer risk among SOT recipients. This cohort study used linked data from the US Scientific Registry of Transplant Recipients and 34 population-based cancer registries, comprising 92% of the US SOT recipient population from 1995 to 2019. Data were analyzed from March to September 2025. Pretransplant cancer diagnosis. Incidence rate ratios (IRRs) were used to compare risk of posttransplant cancer among SOT recipients with vs without pretransplant cancer, adjusted for attained age, sex, and transplanted organ, for 581 combinations of pretransplant and posttransplant cancer types. IRRs were compared with standardized incidence ratios (SIRs), which assess subsequent cancer risk among cancer survivors in the general population, using US cancer registry data. A total of 520 424 SOT recipients were evaluated in the analysis; the median (IQR) age at transplant was 52 (41-59) years. Seven types of pretransplant cancer were significantly associated with a risk of the same type of cancer after transplant (Bonferroni-corrected P value <8.6 × 10-5): breast (IRR, 3.71, 95% CI, 3.04-4.48), melanoma of the skin (IRR, 10.4; 95% CI, 7.43-14.1), lung (IRR, 3.65; 95% CI, 2.67-4.86), kidney (IRR, 2.34; 95% CI, 1.94-2.79), urinary bladder (IRR, 3.72; 95% CI, 2.44-5.39), liver (IRR, 1.73; 95% CI, 1.39-2.14), and colorectum (IRR, 2.38; 95% CI, 1.61-3.37). Other significant associations included liver followed by lung cancer (IRR, 1.63; 95% CI, 1.48-1.80) or by prostate cancer (IRR, 1.71; 95% CI, 1.53-1.92), urinary bladder followed by lung cancer (IRR, 2.55; 95% CI, 1.93-3.29), kidney followed by thyroid cancer (IRR, 2.87; 95% CI, 1.87-4.17), and intrahepatic bile duct followed by pancreatic cancer (IRR, 8.56; 95% CI, 3.66-16.7). These IRRs were lower than the corresponding SIRs for cancer survivors in the general population for 3 combinations of pretransplant and posttransplant cancer types (liver-liver, kidney-kidney, and lung-lung). This cohort study found that SOT recipients with pretransplant cancer had an elevated risk of posttransplant cancer, particularly of the same cancer type. These patterns likely reflect shared genetic or environmental risk factors. Among SOT recipients who had kidney, liver, or lung cancer before transplant, posttransplant cancer of the same organ may be associated with the underlying end-stage organ disease. Targeted cancer prevention and screening could benefit SOT recipients who have survived a cancer diagnosis before a transplant.

Metachronous bilateral conversion in initially unilateral retinoblastoma is uncommon but clinically consequential, potentially requiring intensified treatment and carrying worse prognosis. Clarifying how age at diagnosis refines genetic-risk stratification could enable safer, more efficient surveillance protocols. To estimate the incidence and timing of metachronous bilateral conversion in unilateral retinoblastoma and assess whether age at diagnosis and RB1 testing are associated with bilateral conversion risk. This was a retrospective cohort study at a tertiary center in Shanghai, China, including 1108 consecutive children with initially unilateral retinoblastoma diagnosed from July 2010 to October 2024 (after exclusions for short follow-up [n = 139], missing data [n = 53], or synchronous bilateral disease [n = 10]). The median (IQR) follow-up was 43.4 (24.2-67.6) months. Age at diagnosis and RB1 genetic status/subtypes assessed by next-generation sequencing and multiplex ligation-dependent probe amplification, including penetrance class (high vs low) and mosaic vs germline categorization. Time to metachronous bilateral conversion; cumulative incidence functions with death as a competing risk; spatial distribution of fellow-eye tumors. Among 1108 patients (median [IQR] age at diagnosis, 22.2 [12.0-31.4] months; 591 [53.3%] male), 24 (2.2%) developed metachronous bilateral disease. At 24 months, cumulative incidence was 2.2% (95% CI, 1.3-3.1) overall. By genetic status, the 24-month cumulative incidence was 24.8% (95% CI, 13.8-35.9) in RB1 variant-positive vs 1.6% (95% CI, 0.0-3.1) in RB1 variant-negative patients. Among RB1 variant-positive patients, risk clustered among those diagnosed before 9 months, whereas no conversions were observed among those diagnosed at older than 9 months. Four RB1 variant-negative patients who were initially diagnosed at notably late ages (20.9, 42.7, 79.6, and 118 months) subsequently converted; these cases likely represent undetected low-level mosaicism, somatic variants below detection thresholds, or rare genomic events not captured by standard sequencing panels. Fellow-eye tumors did not involve macula and showed a nasal-predominant distribution. The findings in this study suggest that age at diagnosis may refine genetic risk stratification for metachronous bilateral conversion. RB1 variant-positive patients diagnosed at 9 months or later represent a very low-risk subgroup that may warrant surveillance deescalation, while rare late conversions in RB1 variant-negative patients necessitate continued long-term monitoring.

Older adults with acute myeloid leukemia (AML) have inferior outcomes, yet current genetic risk models do not explicitly account for how age modifies the prognostic impact of molecular features. We hypothesized that integrating apoptosis and p53-related gene expression with recurrent mutations would improve prediction of complete remission (CR) and 2-year overall survival (OS), particularly across age groups. Using the BeatAML2 dataset (805 patients; 942 specimens), we built two cohorts: a clinical cohort of 916 adults with full data and an expression-linked cohort of 852 with matched RNA-seq. Patients were divided into four age groups 18-30, 30-45, 45-60, and 60+ years. We tested whether adding expression of 12 apoptosis and p53-related genes to five well-known mutations, that is TP53, NPM1, FLT3, RUNX1, and ASXL1, could improve the prediction of CR and 2-year OS. Adding gene expression improved predictive performance across models. For 2-year OS, AUCs rose from 0.765 to 0.772 in XGBoost, 0.703 to 0.843 in Random Forest, and 0.697 to 0.721 in Logistic Regression. For CR, performance improved from 0.770 to 0.851 in XGBoost, 0.811 to 0.861 in Random Forest, and 0.731 to 0.696 in Logistic Regression. Calibration was strongest for tree-based models, and reclassification improved most with XGBoost. Multivariable regression confirmed TP53 as the most adverse marker for OS (HR: 3.07), with added risk from ASXL1 (HR: 1.53) and FLT3 (HR: 1.39). NPM1 increased the chance of remission (OR: 2.47) but did not extend survival. SHAP analysis showed that age remained the leading predictor of OS. Among genes, CHEK2 expression was most important for survival, especially in patients 60 years and older, while CCNG1 expression best predicted remission, along with BAX and MCL1. These results demonstrate that combining gene expression with recurrent mutations makes risk prediction more accurate, especially in older patients who formed the largest group and had the poorest outcomes. Although treatment variables were not included and analysis focused on selected genes, these findings support incorporation of expression-based features into genetic risk models and warrant prospective validation. The authors have confirmed clinical trial registration is not needed for this submission.

Most causal variants for complex diseases are expected to affect gene regulation in a cell- and context-specific manner. Hence, identification of such dynamically functioning variants requires functional readouts in disease-relevant tissues and context. In this study, we prioritized causal variants for psoriasis by adding functional annotations from disease-relevant cells. We demonstrate that disease-relevant immune cells, unlike most other tissues, possess functional annotations that match candidate causal SNPs. Specifically, we identified an eQTL, rs4672505, that reduces B3GNT2 gene expression only in Th1/Th17 cells with a memory phenotype, i.e., antigen-experienced T helper cells. This eQTL, a likely causal variant, also matched an enhancer chromatin mark exclusive to memory T helper cells and absent in other tissues. A disease-risk allele A at the eQTL correlates with reduced expression of the B3GNT2 glycosyltransferase. B3GNT2 deficiency in murine models reduces the glycosylation of the CD28 co-receptor involved in the CD28/B7 co-stimulation pathway and results in increased T cell activation upon antigen stimulation. We hypothesize that the risk allele A in patients increases the activation of memory Th1/Th17 cells upon re-exposure to antigens, which constitutes “signal 1”. Increased reactivity to antigens depends on “signal 2” via CD28/B7 co-stimulation from antigen-presenting cells that need to encounter microbial products. Hence, this genetic risk mechanism lies at the nexus of the response to specific antigens and microbial exposure, for instance, infection or vaccination, both of which are known to exacerbate psoriasis.

Maternal (versus paternal) type 1 diabetes is associated with a relative reduction in type 1 diabetes risk in offspring during early life. To determine whether this effect extends into later life. To clarify the importance of intrauterine exposure to maternal type 1 diabetes, and baseline genetic susceptibility in this context. We compared the proportion of individuals with type 1 diabetes diagnosed age 0-88 years with affected mothers and fathers across five observational studies (n=11,475), and used random-effects meta-analyses to generate overall effect estimates. We examined this by age at diagnosis, and timing of parental diagnosis relative to offspring birth. We compared the type 1 diabetes genetic risk score (T1D-GRS2) of individuals with affected mothers and fathers. Almost half as many individuals with type 1 diabetes had an affected mother versus father (OR 0.55 (95% CI 0.48, 0.64), p<0.0001). A lower proportion of individuals with affected mothers than fathers was apparent even amongst individuals diagnosed as adults (>18 years) (OR 0.63 (95% CI 0.43, 0.91), p=0.01). The lower proportion of individuals with maternal versus paternal type 1 diabetes was only observed if maternal diagnosis preceded offspring birth (OR 0.51 (95% CI 0.37, 0.70), p<0.001 versus OR 0.97 (95% CI 0.69, 1.38), p=0.87 after birth). T1D-GRS2 was similar between individuals with affected mothers and fathers (p=0.25). Our analyses suggest intrauterine exposure to maternal type 1 diabetes is associated with long-lasting relative protection against offspring type 1 diabetes, which is independent of genetic susceptibility as measured by T1D-GRS2.

Tobacco smoking is a leading cause of global mortality, with cessation being the primary prevention strategy. Nicotine addiction has a genetic component; the rs503464 single nucleotide polymorphism (SNP) in the CHRNA5 gene is associated with smoking cessation therapy success. However, the impact of communicating genetic risk to patients remains unclear. This study evaluated whether knowledge of the rs503464 genotype influences smoking cessation rates. 270 smokers were enrolled and randomized into two groups: informed and uninformed of their rs503464 genotype. All participants received standard pharmacological-behavioral interventions. Cessation rates were assessed at 1, 3, 6, and 12 months. Multivariable logistic regression models analyzed the effect of knowing the rs503464 genotype and other variables on cessation success. Among the 219 subjects who started prescribed smoking cessation medication, no significant differences in cessation rates were observed between participants informed or not informed of their rs503464 genotype at any follow-up point (P > 0.05). Male gender and higher baseline carbon monoxide levels were associated with lower success rates at three months. The medications used were equally effective. Communication of the rs503464 genotype did not influence smoking cessation success, proving that it does not disturb this process. This result opens the possibility of using genetic information to personalize anti-smoking treatment.

To explore the contribution of genetic risk factors to isolated superior mesenteric artery dissection (ISMAD), this study detected variations in known arterial dissection-related genes in a cohort of patients with symptomatic ISMAD. Thirty-two patients were recruited. Whole-exome sequencing was conducted on blood samples from all participants and 83 controls. Prevalence, clinical characteristics, treatments, and causative gene carriers were also studied. Eleven (34.4%) patients with ISMAD had pathogenic variants in COL3A1 (n = 3), COL12A1 (n = 3), TLN1 (n = 1), FN1 (n = 2), and TNXB (n = 2). Pathogenic variants in the COL3A1 and COL12A1 genes are strongly correlated with ISMAD. In 9.4% (3/32) of the patients with ISMAD, conservative treatment failed and further endovascular treatment was required. Among them, 2 (66.7%) harbored pathogenic mutations in COL3A1. Pathogenic variants in the COL3A1 gene are associated with a high predisposition to endovascular treatment (P = .02). COL3A1, COL12A1, and TLN1 mutations may be risk factors for ISMAD. A small proportion of patients with ISMAD and carrying pathogenic mutations in COL3A1 were more likely to experience more severe arterial tearing and require endovascular treatment.