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

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

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Grey matter abnormalities in children and adolescents with functional neurological symptom disorder

Objective: Functional neurological symptom disorder refers to the presence of neurological symptoms not explained by neurological disease. Although this disorder is presumed to reflect abnormal function of the brain, recent studies in adults show neuroanatomical abnormalities in brain structure. These structural brain abnormalities have been presumed to reflect long-term adaptations to the disorder, and it is unknown whether child and adolescent patients, with illness that is typically of shorter duration, show similar deficits or have normal brain structure. Method: High-resolution, three-dimensional T1-weighted magnetic resonance images (MRIs) were acquired in 25 patients (aged 10–18years) and 24 healthy controls. Structure was quantified in terms of grey matter volume using voxel-based morphometry. Post hoc, we examined whether regions of structural difference related to a measure of motor readiness to emotional signals and to clinical measures of illness duration, illness severity, and anxiety/depression. Results: Patients showed greater volumes in the left supplementary motor area (SMA) and right superior temporal gyrus (STG) and dorsomedial prefrontal cortex (DMPFC) (corrected p<0.05). Previous studies of adult patients have also reported alterations of the SMA. Greater SMA volumes correlated with faster reaction times in identifying emotions but not with clinical measures. Conclusions: The SMA, STG, and DMPFC are known to be involved in the perception of emotion and the modulation of motor responses. These larger volumes may reflect the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness to organize self-protectively in the context of the long-standing relational stress that is characteristic of this disorder. Keywords: Functional neurological symptom disorder, Conversion disorder, Brain volume, MRI, Psychogenic non-epileptic seizure

Microstructural white matter changes in the corpus callosum of young people with Bipolar Disorder: a diffusion tensor imaging study.

To date, most studies of white matter changes in Bipolar Disorder (BD) have been conducted in older subjects and with well-established disorders. Studies of young people who are closer to their illness onset may help to identify core neurobiological characteristics and separate these from consequences of repeated illness episodes or prolonged treatment. Diffusion tensor imaging (DTI) was used to examine white matter microstructural changes in 58 young patients with BD (mean age 23 years; range 16-30 years) and 40 controls. Whole brain voxelwise measures of fractional anisotropy (FA), parallel diffusivity (λ//) and radial diffusivity (λ⊥) were calculated for all subjects. White matter microstructure differences (decreased FA corrected p<.05) were found between the patients with BD and controls in the genu, body and splenium of the corpus callosum as well as the superior and anterior corona radiata. In addition, significantly increased radial diffusivity (p<.01) was found in the BD group. Neuroimaging studies of young patients with BD may help to clarify neurodevelopmental aspects of the illness and for identifying biomarkers of disease onset and progression. Our findings provide evidence of microstructural white matter changes early in the course of illness within the corpus callosum and the nature of these changes suggest they are associated with abnormalities in the myelination of axons

A Meta-analysis of neuropsychological functioning in first-episode bipolar disorders

Broad neuropsychological deficits have been consistently demonstrated in well-established bipolar disorder. The aim of the current study was to systematically review neuropsychological studies in first-episode bipolar disorders to determine the breadth, extent and predictors of cognitive dysfunction at this early stage of illness through meta-analytic procedures. Electronic databases were searched for studies published between January 1980 and December 2013. Twelve studies met eligibility criteria (N = 341, mean age = 28.2 years), and pooled effect sizes (ES) were calculated across eight cognitive domains. Moderator analyses were conducted to identify predictors of between-study heterogeneity. Controlling for known confounds, medium to large deficits (ES ≥ 0.5) in psychomotor speed, attention and working memory, and cognitive flexibility were identified, whereas smaller deficits (ES 0.20-0.49) were found in the domains of verbal learning and memory, attentional switching, and verbal fluency. A medium to large deficit in response inhibition was only detected in non-euthymic cases. Visual learning and memory functioning was not significantly worse in cases compared with controls. Overall, first-episode bipolar disorders are associated with widespread cognitive dysfunction. Since euthymia was not associated with superior cognitive performance in most domains, these results indicate that even in the earliest stages of disease, cognitive deficits are not mood-state dependent. The current findings have important implications for whether cognitive impairments represent neurodevelopmental or neurodegenerative processes. Future studies need to more clearly characterise the presence of psychotic features, and the nature and number of previous mood episodes.11 page(s

Entire BD group analysis.

<p>Panel A: Regions of significantly reduced FA in patients with BD (depicted in red/orange) compared to controls [CC = corpus callosum; ACR = anterior corona radiata]. All significant regions are cluster thresholded at p<.05 and corrected for multiple comparisons. Panel B: A region of significantly increased radial diffusivity within the body of the corpus callosum in patients with BD (depicted in blue) compared to controls.</p

Clusters of significantly decreased FA in patients with bipolar disorder compared to healthy controls (anatomical loci are presented in MNI coordinates).

<p>Clusters of significantly decreased FA in patients with bipolar disorder compared to healthy controls (anatomical loci are presented in MNI coordinates).</p