COVID-19 and obesity are complex conditions marked by immune and metabolic dysfunction, with the former still ranking among the leading causes of death from infectious diseases worldwide and the latter reaching pandemic proportions. Clinical evidence consistently shows that obesity increases the risk of severe COVID-19, yet the biological mechanisms underlying this association remain unclear. Given their physiological and clinical overlap, they may share genetic pathways. We investigated genetic variants jointly associated with body mass index (BMI) and COVID-19 using publicly available genome-wide data. A conjunctional false discovery rate (conjFDR) approach identified shared variants between BMI and three COVID-19 phenotypes: infection, hospitalization and very severe respiratory illness. Functional annotation and pathway enrichment analyses were performed to explore the biological context of these variants, followed by a phenome-wide association study (PheWAS) to characterize pleiotropy. Shared variants were enriched in immune, metabolic and hormonal signaling pathways, including metal ion transport and glycosylation. The overlap with BMI was strongest for hospitalized and severe cases, suggesting common mechanisms underlying disease progression rather than infection. These findings suggest a biologically meaningful genetic overlap between obesity and COVID-19 severity, highlighting pleiotropy as a key feature in complex disease interactions and potential shared therapeutic targets.
Giulia Souza da Costa, C. Bandeira, Nicolas Pereira Ciochetti et al.· Royal Society Open Science· 0 citations
Attention-Deficit/Hyperactivity Disorder (ADHD) is often accompanied by other psychiatric and somatic conditions. Telomere shortening as an accelerated biological aging marker may underlie this aggregate burden. Telomere length (TL) has previously been associated with childhood inattention and hyperactivity, as well as other neuropsychiatric conditions. We hypothesize that TL and ADHD may share overlapping genetic influences, suggesting that some of the same genes could affect both cellular aging and ADHD traits. We investigated the pleiotropic and causal associations between these traits. Using the latest and largest publicly available genome-wide association study (GWAS) summary data for ADHD (38,691 cases and 186,843 controls) and TL (472,174 subjects), we tested causality, global and local genetic correlations, and joint genomic effects. Polygenic scores (PGS) were evaluated in an independent clinical sample of 665 ADHD cases and 995 controls, and TL was quantified via qPCR in a subsample of 370 subjects. The pleiotropy analysis showed global and local (a chromosome 17 locus) negative correlations. Shared genomic analysis showed loci enriched across several chromosomes, notably including the same chromosome 17 locus. This locus contains a diverse set of genes involved in many biological pathways impacting core cellular functions, tissue development, cell cycle, and apoptosis. Mendelian randomization indicated a unidirectional causal effect of ADHD on shorter TL across four methods. In our independent clinical sample, TL was shorter in individuals with ADHD. Lastly, higher PGS for longer TL was associated with reduced ADHD symptomatology. Our findings suggest that ADHD may contribute to TL, and genetic predisposition to shorter TL is associated with greater ADHD severity.
M. Tavares, E. Grevet, J. Schuch et al.· Translational Psychiatry· 0 citations
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