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

Namkoong, H.; Edahiro, R.; Fukunaga, K.; Shirai, Y.; Sonehara, K.; Tanaka, H.; Lee, H.; Hasegawa, T.; Kanai, M.; Naito, T.; Yamamoto, K.; Saiki, R.; Hyugaji, T.; Shimizu, E.; Katayama, K.; Takahashi, K.; Harada, N.; Hiki, M.; Matsushita, Y.; Takagi, H.; Aoki, R.; Nakamura, A.; Harada, S.; Sasano, H.; Kabata, H.; Masaki, K.; Kamata, H.; Ikemura, S.; Chubachi, S.; Okamori, S.; Terai, H.; Morita, A.; Asakura, T.; Sasaki, J.; Morisaki, H.; Uwamino, Y.; Nanki, K.; Mikami, Y.; Uchida, S.; Uno, S.; Ishihara, R.; Matsubara, Y.; Nishimura, T.; Ogawa, T.; Ishiguro, T.; Isono, T.; Shibata, S.

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 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.