reSeArcH Article
Extended Data Fig. 6 | Mucosal communities and human genetics.
a, Number of biopsy samples available for each biopsy location and
inflammation status. b, DEGs (Fig. 4a) with newly identified significant
correlations with OTU abundances in biopsies (partial Spearman
correlation conditioned on disease status, BMI, age at consent and sex;
FDR P < 0.05; n = 54 in ileum and n = 52 independent 16S–RNA-seq
pairs; full table in Supplementary Table 33). c, A limited subset of the
microbiome trended with genetic variants in targeted testing, including
the strongest trend shown here of Parabacteroides distasonis with
genotypes of NKX2-3 (a known IBD-associated locus^103 ; boxplots show
median and lower/upper quartiles; whiskers show inner fences). This is
the most significant association by P value among all tested associations
between metagenomic taxa and five known IBD loci (nominal significance
P = 0.006; no associations passed FDR P < 0.05, mixed effect model
with age, sex, antibiotic and immunosuppressant use and first 20 genetic
principal components as covariates while specifying subjects as random
effects; Wald test; n = 84 subjects of European ancestry with exomes and
960 metagenomes; full results in Supplementary Table 34). d, Association
between rs1042712 SNP in the LCT locus and self-reported milk intake
from dietary recall. Self-reported short-term milk intake (from dietary
recalls accompanying stool samples) was significantly associated with
the count of C alleles (29.8% allele frequency) at rs1042712 in the LCT
gene locus using a linear mixed effect model accounting for age, sex, first
20 genetic principal components and with subjects as random effects
(P = 0.028, linear mixed effect regression with Wald test, see Methods).
All available data are plotted for unique subjects of European ancestry
with exome data (per-genotype subject count (GG/GC/CC):50/26/8).
Differences between IBD and non-IBD groups are not statistically
significant (odds ratio 0.27; 95% CI 0.05–1.33; P = 0.10; n = 84 subjects
of European ancestry with exomes and 960 dietary surveys; model: IBD
(yes|no) ~ intercept + SNP + sex + age + PC1–PC20).