Table 3

Rare microbial quantitative trait loci identified by gene-based burden meta-analyses

Chr	SNP*	Gene symbol	Annotation	Microbial taxonomy/pathway	Microbial change†	Meta P value‡	Meta FDR	LifeLines-DEEP cohort		IBD cohort
Chr	SNP*	Gene symbol	Annotation	Microbial taxonomy/pathway	Microbial change†	Meta P value‡	Meta FDR	P value§	Beta¶	P value§	Beta¶
3	3:156 570 689 rs200834448 3:156 710 862	LEKR1	Stop gain, frameshift variant, splice donor variant and intron variant	Superpathway of hexitol degradation bacteria	Increase in IBD/CD/UC	8.42×10^–7	8.25×10^–4	1.84×10^–5	0.61	0.016	0.54
5	rs114285050 rs140458264	GPR151	Stop gain, stop gain	Homolactic fermentation	Increase in IBD/CD	4.78×10^–6	0.0047	0.0032	−1.17	0.00040	−1.40
5	rs114285050 rs140458264	GPR151	Stop gain, stop gain	Glycolysis I from glucose 6-phosphate	Increase in IBD/CD	5.45×10^–6	0.0053	0.0030	−1.17	0.00048	−1.38
5	rs114285050 rs140458264	GPR151	Stop gain, stop gain	Glycolysis II from fructose 6-phosphate	Increase in IBD/CD/UC	4.63×10^–6	0.0045	0.0028	−1.18	0.00044	−1.38
5	rs114285050 rs140458264	GPR151	Stop gain, stop gain	Superpathway of glucose and xylose degradation	Increase in IBD/CD	3.05×10^–6	0.0030	0.015	−0.97	0.00041	−1.39
13	rs139121187 rs150812023	TPTE2	Stop gain, splice donor variant and intron variant	Glycolysis IV plant cytosol	–	4.62×10^–6	0.0045	0.015	1.19	0.00029	2.47
22	rs35742686 rs5030655	CYP2D6	Frameshift variant, frameshift variant	Superpathway of menaquinol-8 biosynthesis I	–	1.45×10^–5	0.014	0.00015	−0.91	0.021	−0.63
22	rs35742686 rs5030655	CYP2D6	Frameshift variant, frameshift variant	Superpathway of demethylmenaquinol-8 biosynthesis	–	1.50×10^–5	0.015	0.00019	−0.90	0.019	−0.65

Eight associations were identified by the gene-based burden test. We collapsed exome-wide protein truncating variants (PTVs) with minor allele frequency <5% into 980 genes. Genetic scores were used instead of single variant dosage in the association analyses in each cohort. Meta-analyses were performed for those associations with discovery p<0.005 and replication p<0.05.
*Rare PTVs located within genes used in the burden test.
†Case-control analysis on microbial data. Significant (FDR<0.05) microbial change in IBD are shown (online supplementary table 7).
‡Meta p value cut-off determined based on the total number of genes (n=980, Bonferroni correction).
§P values from association analyses in each cohort.
¶Effect size in association analyses in each cohort.
CD, Crohn’s disease.