Table 2

Microbial quantitative trait loci associated with microbial taxonomies and pathways identified in a targeted approach

ChrPosAlleleSNPGene symbolAnnotationBacterial taxonomy/pathwayMicrobial change*Meta P value†Meta FDRLifeLines-DEEP cohortIBD cohort
P value‡ P value‡
167 279 881C/Ars74609208 WDR78 Intron variantdTDP-L-rhamnose biosynthesis I1.46×10–5 0.0480.000350.120.0140.12
9139 371 234G/Ars10781497 SEC16A
Synonymous variantSuperpathway of thiamin diphosphate biosynthesis I1.88×10–6 0.00625.33×10–5 −0.150.011−0.14
9139 371 234G/Ars10781497 SEC16A
Synonymous variantThiazole biosynthesis I Escherichia coli Increase in CD2.44×10–6 0.00526.69×10–5 −0.150.012−0.14
1161 524 507T/Crs2238001 MYRF Intron variantSuperpathway of acetyl-CoA biosynthesisIncrease in IBD/CD7.50×10–8 2.5×10–41.47×10–5 −0.200.0014−0.19
1161 524 507T/Crs2238001 MYRF Intron variantSuperpathway of glyoxylate bypass and TCAIncrease in CD6.16×10–7 0.021.04×10–5 −0.220.015−0.16
1161 524 507T/Crs2238001 MYRF Intron variantSuperpathway of glycolysis pyruvate dehydrogenase TCA and glyoxylate bypassIncrease in CD2.73×10–6 0.0092.90×10–5 −0.210.024−0.15
  • The targeted approach identified six significant associations between variants located in IBD-associated genes and microbial taxa and pathways. Three thousand and ten variants in IBD-associated genomic regions and 316 protein truncating variants and 242 microbial taxa and 301 MetaCyc pathways were used in targeted approach. Spearman correlation was performed in the association test in each cohort, followed by a Z-score-based meta-analysis. The discovery significance threshold was 0.001, the replication significance threshold was 0.05 and the final meta threshold was 1.5 ×10−5 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 decided by the number of total variants (n = 3309, Bonferroni correction).

  • ‡P values from association analyses in each cohort.

  • §Correlation coefficients from association analyses in each cohort.

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