Understanding whether and how shared genetic factors contribute to the comorbidity between stress-related disorders (SRDs) and cardiovascular disease (CVD) is important for integrated prevention and treatment, but current evidence remains limited. To address this gap, we integrated Swedish national registers (n = 4,123,631), UK Biobank (n = 502,291), and genome-wide association study summary statistics to explore shared genetic liability between SRDs and six CVD subtypes and to nominate pleiotropic loci, genes, and enriched pathways. Familial coaggregation analyses showed that the SRDs-CVD association attenuated with decreasing genetic relatedness among relatives, supporting the existence of shared genetic influences. Polygenic risk scores for SRDs significantly predicted a higher risk of any CVD and all subtypes (odds ratios = 1.05-1.09), and all SRDs-CVD pairs showed positive genetic correlations (rg = 0.09-0.35), whereas Mendelian randomization (MR) analyses did not support strong causal effects in either direction. Genome-wide cross-trait analyses identified 17 putative pleiotropic loci, and consensus-based gene mapping prioritized 16 putative pleiotropic genes. Enrichment analyses indicated that pleiotropic signals were enriched in processes related to hemostasis and coagulation, circulatory system development, and telomere maintenance. In validation analyses focusing on post-traumatic stress disorder (PTSD), we observed a similar pattern of genetic overlap with CVD and replicated a subset of loci, genes, and pathways. These findings support a genetic comorbidity framework in which shared genetic liability, largely driven by pleiotropic loci, contributes to the co-occurrence of SRDs and CVD and highlight candidate genes and biological processes for future experimental studies.
C. Hou, Yu Zeng, Huazhen Yang et al.· Genomics, Proteomics & Bioin...· 0 citations
Abstract Background Attention-deficit/hyperactivity disorder (ADHD) medications can reduce ADHD symptom severity in individuals with comorbid autism spectrum disorder (ASD). However, clinical guidance on pharmacological treatment of ADHD in this clinical population remains limited and inconsistent. Characterising real-world treatment patterns (ie, initiation timing, medication choices, switching, discontinuation) and the impact of alternative medication choices on clinical outcomes is critical for informing evidence-based management strategies. Objective To (1) characterise ADHD pharmacological treatment patterns in youth with ADHD+ASD versus ADHD alone and (2) assess whether using alternative ADHD medications versus methylphenidate is associated with differential changes in negative clinical outcomes among youth with ADHD+ASD. Methods This is a population-based cohort study using Swedish national registers. The study included children (<13 years) and adolescents (13–17 years) with an incident ADHD diagnosis between 2007 and 2018 and followed-up until 2021, comparing youth with co-occurring ASD (n=24 117) and ADHD alone (n=79 830). Descriptive outcomes included time to pharmacological treatment initiation, medication type, number of medication switches and discontinuations. The primary outcome was changes in rates of inpatient psychiatric hospitalisations, accidental injuries and specialist care visits for substance use, depressive or anxiety disorders in the 1 year after versus the 1 year before medication initiation. Findings Individuals with ADHD+ASD experienced longer delays to treatment initiation (12–14% initiated >12 months after diagnosis vs 7–8% in ADHD alone). Children with ADHD+ASD were slightly more likely to discontinue treatment within 3 months (16% vs 12%) and had the highest average number of medication switches within 3 years (2.6; IQR 0.0–2.0). In within-individual analyses, comparisons of alternative ADHD medications versus methylphenidate did not yield statistically significant differences after correcting for multiple comparisons. Conclusions Children with ADHD+ASD experienced longer delays to treatment initiation and more frequent medication switching compared with those with ADHD only. The effects of alternative ADHD medication options on key negative clinical outcomes appeared similar to those of methylphenidate. Clinical implications These findings suggest that, rather than recommending fixed first-line and second-line treatments for individuals with ADHD-ASD, clinical guidelines should emphasise appropriate training as well as prompt and individualised treatment based on a shared decision-making process.
M. Garcia-Argibay, R. Kuja-Halkola, B. D'Onofrio et al.· BMJ mental health· 0 citations
Individuals with childhood-onset T1D and their full siblings had higher odds of recorded NDC diagnoses, and these findings support access to neurodevelopmental expertise in paediatric diabetes services.
Shengxin Liu, G. Machado, Irzam Hardiansyah et al.· Acta paediatrica· 0 citations
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