ABSTRACT
To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.
ABSTRACT
From the standpoint of a physician, drug safety data include not only information on adverse effects, but also information required to perform drug therapy safely. Drug safety data required by physicians include pharmacological data, name of the drug, history and physical data of patients, and an electronic or paper-based prescribing system at the clinic. Although most physicians are generally interested in drug safety data, a focus is not placed on adverse effects, given that they represent only a minor fraction of what is required for clinical practice and prescribing drugs. Moreover, Japanese physicians, who are busy with daily clinical practice, cannot find the time to extract essential information from what is supplied or to manage, make use, and report adverse events.<Br>Many problems exist in the management of drug safety data, especially for adverse effects, including collection of data, database management, and feedback to physicians. In particular, current adverse effect reporting systems rely too heavily on physicians. In order to improve the sensitivity and management of drug safety data in Japan, it is expected that not only physicians but also pharmacists, paramedical staff, and patients will report drug safety data. One promising possibility is the establishment of a special division at all medical facilities that manages drug safety data. This concept is similar to that of the Governmental Consumer Agency (Shohisha-cho) launched in 2009. As an issue, drug safety traverses all of healthcare, so it may be necessary for the drug safety division to adopt not only specialists whose subspecialties are more focused, but also general physicians.