40 research outputs found

    Genome-wide association studies of brain imaging phenotypes in UK Biobank

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    The genetic architecture of brain structure and function is largely unknown. To investigate this, we carried out genomewide association studies of 3,144 functional and structural brain imaging phenotypes from UK Biobank (discovery data set 8,428 subjects). Here we show that many of these phenotypes are heritable. We identify 148 clusters of associations between single nucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05, when we would expect 21 to replicate by chance. Notable significant, interpretable associations include: iron transport and storage genes, related to magnetic susceptibility of subcortical brain tissue; extracellular matrix and epidermal growth factor genes, associated with white matter micro-structure and lesions; genes that regulate mid-line axon development, associated with organization of the pontine crossing tract; and 17 genes involved in development, pathway signalling and plasticity. Our results provide insights into the genetic architecture of the brain that are relevant to neurological and psychiatric disorders, brain development and ageing

    Eating Beyond Satiety and Body Mass Index

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    Objective: To examine discrete eating behaviours as predictors of body mass and psychological processes through which these behaviours might lead to increased body mass. Method: Three hundred and twenty-nine undergraduate females filled out questionnaires on eating beyond satiety (EBS), snacking, night eating, and hunger as well as the process variables — eating expectancies and self-reported cue reactivity — in an online study. The eating behaviours were regressed on body mass index and mediation analyses were conducted for the process variables. Results: EBS was the strongest predictor of body mass when the other eating behaviours were controlled. The process variables did not mediate the relationship between EBS and body mass. Discussion: EBS may be a discrete variable on which to intervene to prevent and treat overweight and obesity. Further research is needed to elucidate the situational and affective antecedents of EBS

    Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

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    Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell-deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans
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