Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

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 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 × 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.

Identifying factors contributing to increased susceptibility to COVID-19 risk: a systematic review of Mendelian randomization studies

“… 79 , 100 There is one Mendelian randomization study in an East Asian population that also showed a detrimental effect of obesity in severe COVID-19. 88 Others identified new determinants including increased testosterone, 96 and reduced carnitine and acetyl-carnitine 84 was associated with higher risk of COVID-19 severity and hospitalization, respectively. The updated GWAS of COVID-19 HGI included assessment of a wide range of exposures in COVID-19 risk and highlighted increased liability of type 2 diabetes associated with higher risk of COVID-19 susceptibility and hospitalization, although the association was abolished after adjusting for BMI.…”

Association between ABO blood group/genotype and COVID-19 in a Japanese population

“…In this retrospective cohort study, all COVID-19 cases were recruited through the Japan COVID-19 Task Force. 15 From February 2020 to October 2021, data from consecutive patients aged ≥ 18 years who were diagnosed with COVID-19 based on polymerase chain reaction or antigen test and who agreed to participate in the study were entered into an electronic case record form by the attending physicians at the a liated research institutions. We excluded patients who met any of the following exclusion criteria: (i) non-Japanese patients, (ii) patients with incomplete medical records, for example, insu cient data to extract critical outcome information, and (iii) patients for whom genome-wide association study (GWAS) genotyping data were not available (Figure 1).…”

“…We applied stringent quality control (QC) lters to the samples and variants, as described in a previous study. 15 A total of 2,433 COVID-19 cases passed sample QC. Subsequently, we performed genome-wide genotype imputation; the details are described in a previous study.…”

“…Subsequently, we performed genome-wide genotype imputation; the details are described in a previous study. 15 Out of 2,433 COVID-19 cases, 1,790 cases had clinical information. The GWAS data from 611 healthy subjects as reference population were collected by the Department of Statistical Genetics at Osaka University Graduate School of Medicine and the Japan Biological Informatics Consortium and analyzed.…”

“…We have been conducting a nationwide multi-center consortium to overcome the COVID-19 pandemic in Japan. 15,16 This study aimed to investigate the clinical and genetic characteristics of the association between COVID-19 and the ABO blood group/genotype, and to the best of our knowledge, this is the rst such large-scale study in Japan.…”