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

Psychometric Properties and Correlates of Precarious Manhood Beliefs in 62 Nations

Precarious manhood beliefs portray manhood, relative to womanhood, as a social status that is hard to earn, easy to lose, and proven via public action. Here, we present cross-cultural data on a brief measure of precarious manhood beliefs (the Precarious Manhood Beliefs scale [PMB]) that covaries meaningfully with other cross-culturally validated gender ideologies and with country-level indices of gender equality and human development. Using data from university samples in 62 countries across 13 world regions (N = 33,417), we demonstrate: (1) the psychometric isomorphism of the PMB (i.e., its comparability in meaning and statistical properties across the individual and country levels); (2) the PMB’s distinctness from, and associations with, ambivalent sexism and ambivalence toward men; and (3) associations of the PMB with nation-level gender equality and human development. Findings are discussed in terms of their statistical and theoretical implications for understanding widely-held beliefs about the precariousness of the male gender role

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

peer reviewe

2006) Elucidating the effect of final-day dosing of rifampin in induction studies on hepatic drug disposition and metabolism. J Pharmacol Exp Ther

ABSTRACT Because rifampin (RIF) induces hepatic enzymes and inhibits uptake transporters, dosing a drug that is a dual substrate of enzymes and uptake transporters on the final day of an inducing regimen should exhibit less inductive effect than dosing on the following day in the absence of RIF, since RIF decreases drug uptake into liver. In vitro and in vivo rat studies were conducted using digoxin as a model substrate. Digoxin was administered to an uninduced control group to obtain baseline values. The second group (induced with dexamethasone) received digoxin alone, mimicking administration of a test drug 1 day following completion of an induction regimen, whereas the third group (induced) received digoxin with RIF mimicking the concomitant dosing on the final day of an induction regimen. Results from hepatocyte concentration-time course studies showed that compared with uninduced control (26.9 Ϯ 1.3 M ⅐ min/mg), digoxin area under the time-concentration curve (AUC) in induced cells when no RIF is present decreased significantly (13.7 Ϯ 0.9 M ⅐ min/mg; p Ͻ 0.01), suggesting induction of Cyp3a. However, digoxin AUC for induced cells in the presence of RIF (27.3 Ϯ 0.9 M ⅐ min/mg) matched the control. Rat pharmacokinetic studies showed that compared with digoxin clearance in uninduced controls (7.08 Ϯ 1.57 ml/min/kg), digoxin clearance in induced rats increased 2-fold (15.6 Ϯ 3.7 ml/min/kg; p Ͻ 0.001), but when RIF was coadministered in the induced rats, digoxin clearance (7.14 Ϯ 1.24 ml/min/kg) overlapped with control. That is, concomitant dosing of RIF and digoxin masked the inductive effect. To observe full inductive effects, test drugs should be administered 1 day after final dosing of RIF to minimize potential organic anion transporting polypeptide inhibition effects