Additional file 1: of Shared and unique common genetic determinants between pediatric and adult celiac disease

Figure S1. QQ plots showing level of genomic inflation in (a) Paediatric CD and (b) Adult CD groups in north Indian population. Inflation was measured using 3016 independent, neutral-reported variants present on the array (derived from reading and math skills GWAS therefore unlikely to be confounded by the immune signal). FigureS2. Manhattan plots showing association signals in (a) Paediatric CD and (b) Adult CD in north Indian population. (DOCX 254 kb

List of significant (p<0.05) SNPs in and around IL23R gene.

<p>List of significant (p<0.05) SNPs in and around IL23R gene.</p

Association status of 59 GWAS reported UC/CD specific susceptibility loci in a north Indian UC cohort.

<p> <b>^a</b><b>Mc Govern, et al., Genome-wide association identifies multiple ulcerative colitis susceptibility loci (2010) Nat Genet.; 42(4):332–7.</b></p><p> <b>^b</b><b>Monomorphic.</b></p><p> <b>^c</b><b>SNPs not in the Illumina Human600W-Quad used in this study.</b></p><p>*<b>p<0.05.</b></p><p>**<b>Significant after Bonferroni correction.</b></p

Results of the parent-of-origin (POO) analysis in the BTNL2 locus in Dutch UC ulcerative colitis trios (n = 72).

<p>P-value (p-α; ß; γ) and odds ratio (OR-α; ß; γ) of the alpha-, beta-, and gamma-term. Alpha-term indicates the genomic imprinting effect; Beta-term and gamma-term indicate the maternal effect in case the mother carries respectively two and one risk alleles. Significant associations are in bold. P-values displayed in the table are not corrected for multiple testing.</p

Distinct types of parent-of-origin mechanisms tested in this study.

<p>Fig. 1a. Genomic imprinting: Genomic imprinting is characterized by consequent silencing of one allele, depending on the parental origin. In the example shown above a normal situation is displayed on the left and the genomic imprinting is shown on the right; red is the risk allele and bleu is the wild type allele. The maternal genotype is heterozygous, the father’s genotype is homozygous wild-type. Offspring in the left scenario have a normal phenotype since the paternal wild-type allele is expressed in the heterozygous offspring and the mutated allele of the mother is thus rescued by the paternal allele. On the right genomic imprinting is shown, reflecting the α-term in the method used to test for parent of origin effects. In this example there is a significant genomic imprinting effect and the OR >1 so the paternal allele is silenced (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045287#s2" target="_blank">materials and methods</a> section statistical analysis). We assume an additive or recessive model of inheritance. Two possible outcomes are listed, if the offspring inherits the risk allele from the mother and the wild-type allele from the father is subjected to genomic imprinting, then only the risk allele is expressed, thus the offspring is affected by the mutated allele from the mother. Fig. 1b. Maternal effects: Maternal effects are effects of the maternal genotype on the fetal phenotype, irrespective of the fetal genotype, these effects are reflected by the β- and γ-terms in the likelihood ratio test that was used to test for parent of origin effects in our study. In the example given above, the β- and γ-terms are significant with an OR >1, meaning that the risk of disease is higher if the mother carries two or one risk allele respectively. A recessive or co-dominant model is assumed, and higher expression of the mutant allele leads to disease. If the genotype of the offspring is red, then maternal effects cause increased disease risk and if it is green than the normal population risk applies. If the mother is homozygous wild-type, no maternal effects occur. If she is homozygous mutant or heterozygous for the risk allele, the offspring is subjected to maternal effects and thus has an increased disease risk. Note that the wild-type homozygous offspring has a higher disease risk if both parents are heterozygous.</p

Results of the parent-of-origin (POO) analysis of Dutch IBD Trios (n = 181) for the 28 known SNPs shared between ulcerative colitis and Crohn’s disease.

<p>P-value (p-α; ß; γ) and odds ratio (OR-α; ß; γ) of the alpha-, beta-, and gamma-terms. Alpha-term indicates the genomic imprinting effect; Beta-term and gamma-term indicate the maternal effect in case the mother carries respectively two and one risk alleles. N/A not available. Significant associations are shown in bold. P-values displayed in the table are not corrected for multiple testing. <i>*</i>reported SNP not present/captured by the Immunochip, a proxy was used, therefore no risk allele could be reported. r² = 1; <b><i>^§</i></b>r² = 0.03; two independent hits in one gene.</p

Phenotypic characterization of subjects with Crohn’s disease.

<p>Phenotypic characterization of subjects with Crohn’s disease.</p

Phenotypic characterization of subjects with ulcerative colitis.

<p>N/A not available, AOO average age of onset. Cases and disease location are given according to the Montreal classification. for CD L1, L2, L3 and L4; for UC E1, E2, E3. No phenotypic information was available for the German cohort.</p

Results of the parent-of-origin (POO) analysis for the NOD2 variants in Dutch Crohn’s disease trios (n = 111) and replication in German Crohn’s disease trios (n = 598).

<p>P-value (p-α; ß; γ) and odds ratio (OR-α; ß; γ) of the alpha-, beta-, and gamma-terms. P-value of the replication study (p- α; -ß; - γ replication ) of the alpha-, beta-, and gamma-terms<b>.</b> Alpha-term indicates the genomic imprinting effect; Beta-term and gamma-term indicate the maternal effect in case the mother carries respectively two and one risk alleles. Significant associations are in bold.</p>◊<p>Significant after Bonferroni multiple testing correction. P-values displayed in the table are not corrected for multiple testing.</p>*<p>No homozygous mothers are available for beta-term analysis.</p