Genetic polymorphisms which showed a nominal significant value after case-control comparisons (in decreasing significance).

<p>ORs are referred to the mutant genotype or carrier of the mutant allele (specified below “genotype”).</p

Genotypic data (N (%)) for rs4969170 in the original and the replication sets.

<p>AA genotype:</p><p>*: p = 0.0018 OR = 0.59 95% CI 0.42–0.84;</p>#<p>, p = 0.20 95% CI OR = 0.75 (0.46–1.20).</p

Characteristics of the infant/mother pairs studied with breast milk samples available at month 1 and month 4.

<p>Characteristics of the infant/mother pairs studied with breast milk samples available at month 1 and month 4.</p

Associations between breast milk macronutrient classes and hormones to infant serum metabolites at 4 months of age.

<p>Breast milk components were measured at month 1 (a) or month 4 (b). Negative log-transformed P-values are plotted for each metabolite arranged by metabolite group and species. Higher values represented in the outer circles present a higher association between metabolite and predictor. P-values were calculated by linear regression models with the milk compound as independent variable, adjusted for infant sex, breastfeeding status at 4-month blood withdrawal (exclusively BF yes/no), and the infant’s age at blood withdrawal. Random intercepts were modelled for batch number and study centre. P-values were corrected (PLME) for multiple testing using Bonferroni’s methods, this is by dividing the p-value with number of metabolites (n = 184).</p

CONSORT flow diagram.

<p>Of 944 children in the PreventCD-cohort, 196 complete mother/infant pairs with complete sample sets were analysed. 136 pairs were studied for the associations between <i>month 1</i> breast milk composition and infant serum metabolites at age of 4 months and 137 were studied for the associations between <i>month 4</i> breast milk composition and infant serum metabolites at age of 4 months. 87 were studied at both time points.</p

Correlations between breast milk fatty acids percentages to infant serum metabolites at 4 months of age.

<p>Breast milk components were measured at month 1 (a) or month 4 (b). Spearman correlation coefficients are plotted for each metabolite arranged by metabolite group. AA, amino acids; Carn, acylcarnitines; LPC, lysophosphatidylcholines; PC aa, diacyl-phosphatidylcholines; PC ae, acyl-alkyl-phosphatidylcholines SM, sphingomyelins.</p

Faecal microbiota of infants with different HLA-DQ genotype at 7 days of age analysed by qPCR.

1<p>Data are expressed as mean and standard deviation of log cells/g faeces.</p>2<p>Statistical significant differences were calculated using ANOVA and <i>post hoc</i> LSD test. Significant differences were established at p<0.050.</p

Faecal microbiota of breast-fed infants with different HLA-DQ genotype at 7 days of age analysed by qPCR.

1<p>Data are expressed as mean and standard deviation of log cells/g faeces.</p>2<p>Statistical significant differences were calculated using ANOVA and <i>post hoc</i> LSD test. Significant differences were established at p<0.050.</p

Faecal microbiota of infants with different HLA-DQ genotype at 4 months of age analysed by qPCR.

1<p>Data are expressed as mean and standard deviation of log cells/g faeces.</p>2<p>Statistical significant differences were calculated using ANOVA and <i>post hoc</i> LSD test. Significant differences were established at p<0.050.</p

Demographic data of infants under study.

1<p>Data are expressed as mean and standard deviation in brackets.</p>2<p>Infants who were exclusively breast-fed at each sampling time were included in the breast-feeding group.</p>3<p>Infants who received either exclusively formula or both formula and breast-milk were included in the formula-feeding group.</p>4<p>Genetic risk of developing CD was established according to the HLA-DQ genotype (see Materials and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030791#s2" target="_blank">Methods</a> section for details).</p