Cardiovascular health interacts with cognitive and psychological health in complex ways. Yet, little is known about the phenotypic and genetic links of heart-brain systems. Using cardiac and brain magnetic resonance imaging (CMR and brain MRI) data from over 40,000 UK Biobank subjects, we developed detailed analyses of the structural and functional connections between the heart and the brain. CMR measures of the cardiovascular system were strongly correlated with brain basic morphometry, structural connectivity, and functional connectivity after controlling for body size and body mass index. The effects of cardiovascular risk factors on the brain were partially mediated by cardiac structures and functions. Using 82 CMR traits, genome-wide association study identified 80 CMR-associated genomic loci (P < 6.09 × 10-10), which were colocalized with a wide spectrum of heart and brain diseases. Genetic correlations were observed between CMR traits and brain-related complex traits and disorders, including schizophrenia, bipolar disorder, anorexia nervosa, stroke, cognitive function, and neuroticism. Our results reveal a strong heart-brain connection and the shared genetic influences at play, advancing a multi-organ perspective on human health and clinical outcomes.
The Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) study is an adaptive platform trial designed to investigate novel interventions to severe asthma. The study is conducted under a master protocol and utilizes a crossover design with each participant receiving Ivanova et al.
There is increasing concern about the potential effects of anesthesia exposure on the developing brain. The effects of relatively brief anesthesia exposures used repeatedly to acquire serial magnetic resonance imaging scans could be examined prospectively in rhesus macaques. We analyzed magnetic resonance diffusion tensor imaging (DTI) of 32 rhesus macaques (14 females, 18 males) aged 2 weeks to 36 months to assess postnatal white matter (WM) maturation. We investigated the longitudinal relationships between each DTI property and anesthesia exposure, taking age, sex, and weight of the monkeys into consideration. Quantification of anesthesia exposure was normalized to account for variation in exposures. Segmented linear regression with two knots provided the best model for quantifying WM DTI properties across brain development as well as the summative effect of anesthesia exposure. The resulting model revealed statistically significant age and anesthesia effects in most WM tracts. Our analysis indicated there were major effects on WM associated with low levels of anesthesia even when repeated as few as three times. Fractional anisotropy values were reduced across several WM tracts in the brain, indicating that anesthesia exposure may delay WM maturation, and highlight the potential clinical concerns with even a few exposures in young children.
Brain ventricular and subcortical structures are heritable both in size and shape. Genetic influences on brain region size have been studied using conventional volumetric measures, but little is known about the genetic basis of ventricular and subcortical shapes. Here we developed pipelines to extract seven complementary shape measures for lateral ventricles, subcortical structures, and hippocampal subfields. Based on over 45,000 subjects in the UK Biobank and ABCD studies, 60 genetic loci were identified to be associated with brain shape features, 19 of which were not detectable by volumetric measures of these brain structures. Ventricular and subcortical shape features were genetically related to cognitive functions, mental health traits, and multiple brain disorders, such as the attention-deficit/hyperactivity disorder. Vertex-based shape analysis was performed to precisely localize the brain regions with these shared genetic influences. Mendelian randomization suggests brain shape causally contributes to neurological and neuropsychiatric disorders, including Alzheimer's disease and schizophrenia. Our results uncover the genetic architecture of brain shape for ventricular and subcortical structures and prioritize the genetic factors underlying disease-related shape variations.
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