SARS-CoV-2 susceptibility and ACE2 gene variations within diverse ethnic backgrounds

Background Host genetics play a major role in COVID-19 susceptibility and severity. Here, we analyse an ethnically diverse cohort of National Health Service (NHS) patients in the United Kingdom (UK) to assess the association between variants in the ACE2 locus and COVID-19 risk. Methods We analysed whole-genome sequencing (WGS) data of 6,274 participants who were tested for SARS-CoV-2 from the UK's 100,000 Genomes Project (100KGP) for the presence of ACE2 variants and expression quantitative trait loci (eQTLs). Findings We identified a splice site variant (rs2285666) associated with increased ACE2 expression with an overrepresentation in SARS-CoV-2 positive patients relative to 100KGP controls (p = .015), and in hospitalised European patients relative to outpatients in intra-ethnic comparisons (p = .029). We also compared the prevalence of 288 eQTLs, of which 23 were enriched in SARS-CoV-2 positive patients. The eQTL rs12006793 had the largest effect size (d = 0.91), which decreases ACE2 expression and is more prevalent in controls, thus potentially reducing risk of COVID-19. We identified three novel nonsynonymous variants predicted to alter ACE2 function, and showed that three variants (p.K26R, p.H378R, p.Y515N) alter receptor affinity for the viral Spike (S) protein. Variants p.K26R and p.N720D are more prevalent in the European population (p < .001), but Y497H is less prevalent compared to East Asians (p = .020). Interpretation Our results demonstrate that the spectrum of genetic variants in ACE2 may inform risk stratification of COVID-19 patients and could partially explain the differences in disease susceptibility and severity among different ethnic groups. Funding The 100KGP is funded by the National Institute for Health Research and NHS England. Funding was also obtained from Stanford University, Palo Alto.

The Core of the Language Consciousness of an Ethnic Group in Diachronic Aspect: Kazakh Associative Dictionaries

The article discusses the possibility of using the data of free associative experiments (SAE) and associative dictionaries, which can serve as a tool of ethno-psycholinguistic, cultural and sociopsychological research to identify the mental and ethno-cultural specificity of language consciousness and language pictures of the world of different ethnic groups, structuring the core of language consciousness (JAS), determining the basic values of society and, in the case of creating such dictionaries in different time periods, they are able to identify the transformation of the mental climate and value priorities of different generations of the same ethnic group. The content of the article is such intra-ethnic comparisons of associative behavior of the representations of the Kazakh ethnos of the modern and Soviet period in the hierarchy of value priorities, their stability and transformation, reflected in the nuclear zones of the language consciousness of young people of two generations with a forty-year interval. On the basis of the coincidence of the basic values in the conceptual center of the core of language consciousness, the article concludes about a certain stability and immutability of cultural, mental and behavioral traditions of the Kazakh ethnic group.