25 research outputs found

    SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

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    Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

    A first update on mapping the human genetic architecture of COVID-19

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    Oxytocin increases physiological linkage during group therapy for methamphetamine use disorder: a randomized clinical trial.

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    Patients and psychotherapists often exhibit behavioral, psychological, and physiological similarity. Here, we test whether oxytocin-a neuropeptide that can enhance expressivity and social perception-influences time-lagged "linkage" of autonomic nervous system responses among participants and facilitators during group therapy. Physiological linkage estimates (n = 949) were created from ten cohorts, each with two facilitators (n = 5) and four to six participants (n = 48), over six weekly sessions of group therapy for methamphetamine use disorder. All participants of a cohort received oxytocin or placebo intranasally in a randomized double-blind procedure before each session. Cardiac interbeat intervals (IBI) were measured continuously during sessions to estimate physiological linkage, operationalized as one cohort-mate's IBI reactivity during one minute predicting another cohort-mate's IBI reactivity during the following minute. In oxytocin cohorts, participants and facilitators experienced significant physiological linkage to their cohort-mates (i.e., their physiological responses were predicted by the prior responses of their cohort-mates) and significantly more linkage than people in placebo cohorts. Both effects occurred during the first and second sessions but not later sessions. Results suggest that oxytocin may enhance psychosocial processes often associated with linkage-such as social engagement-in groups and highlight oxytocin's potential to improve group cohesion during group therapy.Clinical Trials Registration: NCT02881177, First published on 26/08/2016

    BDNF serum concentrations show no relationship with diagnostic group or medication status in neurodegenerative disease.

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    Brain-derived neurotrophic factor (BDNF) is a growth factor implicated in neuronal survival. Studies have reported altered BDNF serum concentrations in patients with Alzheimer's disease (AD). However, these studies have been inconsistent. Few studies have investigated BDNF concentrations across multiple neurodegenerative diseases, and no studies have investigated BDNF concentrations in patients with frontotemporal dementia. To examine BDNF concentrations in different neurodegenerative diseases, we measured serum concentrations of BDNF using enzyme-linked immunoassay in subjects with behavioral-variant frontotemporal dementia (bvFTD, n=20), semantic dementia (SemD, n=16), AD (n=34), and mild cognitive impairment (MCI, n=30), as well as healthy older subjects (HS, n=38). BDNF serum concentrations were compared across diagnoses and correlated with cognitive tests and patterns of brain atrophy using voxelbased morphometry. We found small negative correlations between BDNF serum concentrations and some of the cognitive tests assessing learning, information processing speed and cognitive control in complex situations, however, BDNF did not predict disease group membership despite adequate power. These findings suggest that BDNF serum concentration may not be a reliable diagnostic biomarker to distinguish among neurodegenerative diseases

    Impaired Recognition and Regulation of Disgust Is Associated with Distinct but Partially Overlapping Patterns of Decreased Gray Matter Volume in the Ventroanterior Insula

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    BACKGROUND: The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. METHODS: We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased grey matter volume at a significance level p<0.05 corrected for family-wise error across the whole brain and within the insula. RESULTS: Patients with behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) were most likely to exhibit disgusting behaviors and were, on average, the most impaired at recognizing disgust in others. Imaging analysis revealed that patients who exhibited disgusting behaviors had significantly less grey matter volume bilaterally in the ventral anterior insula. A region of interest analysis restricted to bvFTD and svPPA patients alone confirmed this result. Moreover, impaired recognition of disgust was associated with decreased grey matter volume in the bilateral ventroanterior and ventral middle regions of the insula. There was an area of overlap in the bilateral anterior insula where decreased grey matter volume was associated with both the presence of disgusting behavior and impairments in recognizing disgust. CONCLUSION: These findings suggest that regulating disgusting behaviors and recognizing disgust in others involve two partially overlapping neural systems within the insula. Moreover, the ventral anterior insula is required for both processes
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