ERN-ITHACA-European Reference Network, Soria, Spain.
Pediatric Neurology Unit, Department of Pediatrics, Navarra Health Service Hospital, Pamplona, Spain.
Elife. 2024 Oct 3;13:RP93666. doi: 10.7554/eLife.93666.
The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations ( and ). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in . Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.
严重 COVID-19 的遗传基础已得到深入研究,并且已经确定了人群之间共享的许多遗传风险因素。然而,非欧洲人群的样本量减少限制了特定人群常见风险基因座的发现。在 SCOURGE 联盟中的第二项嵌套研究中,我们对混合人群中的 COVID-19 住院进行了全基因组关联研究(GWAS),其中包括由 SCOURGE 和 COVID-19 宿主遗传倡议的其他七个参与研究招募的总共 4702 名住院患者。我们确定了四个全基因组显著关联,其中两个构成了新的基因座,并且首先在拉丁美洲人群中发现(和)。跨种族荟萃分析揭示了中的另一个新的跨人群风险基因座。最后,我们评估了跨血统多基因风险评分在 SCOURGE 混合美国队列中的表现。这项研究是迄今为止针对混合拉丁美洲人群中 COVID-19 住院进行的最大规模的 GWAS。这使得新的风险基因座得以揭示,并强调了在基因组研究中需要考虑人群多样性。