A genome-wide association study for gut metagenome in Chinese adults illuminates complex diseases

摘要

a The enterotype plot of 618 individuals in discovery cohort. Two clusters were shown with red dots representing Bacteroides-dominated enterotype (440 individuals) and blue dots representing Prevotella-dominated enterotype (178 individuals). The first two principal components (PCoA1 and PCoA2) are shown, with the amount of variation explained are reported for each axe. b The enterotype plot of 663 individuals in replication cohort. Two clusters were shown with red dots representing Bacteroides-dominated enterotype (473 individuals) and blue dots representing Prevotella-dominated enterotype (190 individuals). c The minor allele G of SNP rs13045408 at BTBD3-LINC01722 were positively correlated with Bacteroides abundance and negatively correlated with Prevotella abundance in discovery cohort. However, SNP rs1453213 at OXR1 had opposite effect effects to enterotypes compared with that of rs13045408. d rs13045408 and rs1453213 associated with “Bacteroides-Prevotella” enterotype in replication cohort (PP-B = 0.061 and 0.024, respectively). e Manhattan plots of the host genetic variants associated with microbiome β-diversity (computed as Bray–Curtis dissimilarity matrix). The red line represents a genome-wide significant P value (5 × 10–8) and blue line represents suggestive P value (10−5). Five top loci were marked with gene name. f The replicated P value in this study for the 391 SNPs previously reported to be significantly associated with the microbiome. 12 SNPs are successfully replicated at P 1.7 × 10−4 = 0.05/296 (blue line), nine of which were most associated with Bacteroides stercoris.