Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Listen to the noise: noise is beneficial for cognitive performance in ADHD.

Background: Noise is typically conceived of as being detrimental to cognitive performance. However, given the mechanism of stochastic resonance, a certain amount of noise can benefit performance. We investigate cognitive performance in noisy environments in relation to a neurocomputational model of attention deficit hyperactivity disorder (ADHD) and dopamine. The Moderate Brain Arousal model (MBA; Sikström &amp; Söderlund, 2007) suggests that dopamine levels modulate how much noise is required for optimal cognitive performance. We experimentally examine how ADHD and control children respond to different encoding conditions, providing different levels of environmental stimulation.Methods: Participants carried out self-performed mini tasks (SPT), as a high memory performance task, and a verbal task (VT), as a low memory task. These tasks were performed in the presence, or absence, of auditory white noise.Results: Noise exerted a positive effect on cognitive performance for the ADHD group and deteriorated performance for the control group, indicating that ADHD subjects need more noise than controls for optimal cognitive performance.Conclusions: The positive effect of white noise is explained by the phenomenon of stochastic resonance (SR), i.e., the phenomenon that moderate noise facilitates cognitive performance. The MBA model suggests that noise in the environment, introduces internal noise into the neural system through the perceptual system. This noise induces SR in the neurotransmitter systems and makes this noise beneficial for cognitive performance. In particular, the peak of the SR curve depends on the dopamine level, so that participants with low dopamine levels (ADHD) require more noise for optimal cognitive performance compared to controls.<br/

Sex Differences in Spatial Abilities: An Evolutionary Explanation

MacIntyre’s (1997) review of gender differences in spatial abilities overlooked findings generated by the metatheory of evolutionary psychology. This oversight reflects an underlying hostility within the social sciences towards the use of evolutionary theory in the study of human behaviour and cognition. As a remedy, this paper outlines the theoretical background of evolutionary psychology, focusing on the insights evolutionary psychology offers for cognitive gender differences research, with particular reference to gender differences in spatial abilities