Table 1

Microbial quantitative trait loci associated with microbial taxonomies and pathways identified in a whole-exome-wide approach

ChrPosAlleleSNPGene symbolAnnotationMicrobial taxonomy/pathwayMicrobial change*Meta P value†Meta FDRLifeLines-DEEP cohortIBD cohort
P value‡ P value‡
176 344 011A/Crs1493367 MSH4 Splice region variant and intron variantSuperpathway of sulfur amino acid biosynthesis Saccharomyces cerevisiae 5.30×10–7 0.0411.36×10–5 0.170.0120.15
4190 862 155T/Grs4145515 FRG1 5 prime UTR premature start codon gain variantGenus Actinomyces 5.29×10–7 0.0413.53×10–5 0.190.00450.20
6144 999 763A/Crs9376837 UTRN Intron variantSpecies Parabacteroides merdae (strain Parabacteroides merdae)4.31×10–7 0.0334.44×10–6 −0.180.031−0.15
72 566 028G/Ars12700028 LFNG Synonymous variantFamily Acidaminococcaceae1.31×10–7 0.013.89×10–6 0.270.0100.25
115 142 270T/Grs10837375 OR52E2-OR52A5Intergenic regionGlycogen biosynthesis I from ADP-D-glucose2.45×10–7 0.0196.63×10–6 0.150.0110.12
1161 524 507T/Crs2238001 MYRF Intron variantSuperpathway of glyoxylate bypass and TCAIncrease in CD6.16×10–7 0.0481.04×10–5 −0.220.015−0.16
1161 524 507T/Crs2238001 MYRF Intron variantSuperpathway of acetyl-CoA biosynthesisIncrease in IBD/CD7.50×10–8 0.00581.47×10–5 −0.200.0014−0.19
1778 188 963G/Ars4889839 SGSH Intron variantSpecies Ruminococcus sp 5 1 39BFAA (strain GCF 000159975)Decrease in UC6.07×10–7 0.0471.25×10–5 −0.150.0159−0.14
1952 376 507T/Crs2288868 ZNF577 Missense variantSpecies Haemophilus parainfluenzae 4.56×10–7 0.0357.84×10–6 0.320.0150.24
2224 564 477C/Trs17854875 CABIN1 Synonymous variantD-glucarate degradation IIncrease in CD4.15×10–7 0.0321.82×10–5 0.270.00570.21
2250 471 620A/Crs5845912 IL17REL Intergenic regionSpecies Alistipes indistinctus (strain GCF 000231275)4.36×10–7 0.0336.18×10–6 −0.240.024−0.24
  • The whole-exome-wide approach identified 11 significant associations between variants located in 10 genes and microbial taxa and pathways. Seventy three thousand one hundred and sixty-four common variants (minor allele frequency >5%), 242 taxa and 301 pathways (corrected for all covariates) were used in the association analyses. Spearman correlation was performed in the association test in each cohort, followed by a Z-score-based meta-analysis. The discovery significance threshold was p<5 ×10−5, the replication significance threshold was p<0.05 and the final meta threshold was 6.83 ×10−7, corresponding to FDR<0.05.

  • *Case-control analysis on microbial data. Significant (FDR <0.05) microbial change in IBD are shown (online supplementary table 7).

  • †Meta p value threshold was decided by the number of total variants (n = 73 164, Bonferroni correction).

  • ‡P values from association analyses in each cohort.

  • §Correlation coefficients from association analyses in each cohort.

  • CD, Crohn’s disease; CoA, coenzyme A; TCA, tricarboxylic acid cycle.