Numerous host extrinsic and intrinsic factors affect the gut microbiota composition, but their cumulative effects do not sufficiently explain the variation in the microbiota, suggesting contributions of missing factors. The Japanese population possesses homogeneous genetic features suitable for genome-wide association study (GWAS). Here, we performed GWASs for human gut microbiota using 1068 healthy Japanese adults. To precisely evaluate genetic effects, we corrected for the impacts of numerous host extrinsic and demographic factors by introducing them as covariates, enabling us to discover five loci significantly associated with microbiome diversity measures: HS3ST4, C2CD2, 2p16.1, 10p15.1, and 18q12.2. Nevertheless, these five variants explain only a small fraction of the variation in the gut microbiota. We subsequently investigated the heritability of each of the 21 core genera and found that the abundances of six genera are heritable. We propose that the gut microbiota composition is affected by a highly polygenic architecture rather than several strongly associated variants in the Japanese population.

许多宿主的外在和内在因素会影响肠道微生物群的组成，但它们的累积效应并不能充分解释微生物群的变化，这表明缺失因素的贡献。日本人群拥有适合全基因组关联研究（GWAS）的同质遗传特征。在这里，我们对 1068 名健康的日本成年人进行了人类肠道微生物群的 GWAS。为了精确评估遗传效应，我们通过将许多宿主外在和人口因素作为协变量引入来校正它们的影响，使我们能够发现与微生物组多样性测量显着相关的五个位点： HS3ST4 、 C2CD2、2p16.1、10p15.1和18q12.2。然而，这五种变异只能解释肠道微生物群变异的一小部分。我们随后调查了 21 个核心属的遗传力，发现 6 个属的丰度是可遗传的。我们认为，肠道微生物群组成受到高度多基因结构的影响，而不是日本人群中几种密切相关的变异的影响。