Stepwise identification of predictors of T1D Incidence (a) by domain and (b) final.

<p>The lines are the 35/77 variables with p<0.2. Green bars indicate variables that were excluded during the stepwise multiple regression (the length of the bar indicates the number of steps at which it was excluded). Blue bars indicate that variables were selected after SMLR was applied. The dark blue bars indicate that the independent predictors of T1D were highly significant; panel (A): in the by-domain analysis; panel (B): in the final model. The final analysis was performed on the variables selected in the by-domain analysis (shown in dark blue in panel (A). Abbreviations: Dom: Domain, PM: particular matter, UV: ultraviolet, GDP: Gross Domestic Product, BMI: Body Mass Index, CVD: Cardiovascular Diseases, CA: Cancer, DM: Diabetes Mellitus, CHRD: Chronic Respiratory Diseases, Adj.R2: Adjusted-R2. (a) Variable dropped after applied Akaike information criterion (AIC).</p

Final Stepwise MLR model.

<p>The model included all significant predictors found in the analyses by domain.</p><p>(a) Among 1-year-olds (%)</p><p>(b) age-standardized estimate.</p><p>Final Stepwise MLR model.</p

The predicted incidence of T1D among 80 countries vs. the observed incidence.

<p>Red dot: Finland. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118298#pone.0118298.s003" target="_blank">S2 Fig.</a> for predicted indices obtained after 10-fold Cross-validation.</p

Baseline characteristics of subjects.

<p>Baseline characteristics of subjects.</p

Adjusted hazard ratio according to sex and paternal occupation.

<p>The effect of paternal occupation on the hazard ratio on [31; 99 y] is estimated for each completed dataset thanks to a Cox proportional hazard model, and then combined following Rubin’s rules. Also given are estimates on legitimate children alone, for whom no imputation of paternal occupations is needed. For both sexes, the reference group is that of craftsmen’ children. Estimated effects are given ± standard error.</p

Survival curves by sex and occupation of the father.

<p>The survival functions are based on the pooled 10 completed datasets created by multiple imputation. In each plot, grey lines are survival functions for the other sex. Estimates of median ages at death based on B = 500 bootstrap samples are drawn in the lower part of the plots. The survival functions of the French 1915 male and female cohorts as given by the Human Mortality Database (HMD) are also drawn. Child mortality was known to be higher in the “departement” (district) of Paris than nationwide at the beginning of the XX^th century. Also drawn are HMD survival functions corrected for this excess child mortality (cor. HMD), based on the quotients of mortality ₁q₀ and ₄q₁ as given by ref. 20, which relate to the 1901–1905 female cohort. 1915 HMD ₁q₀ and ₄q₁ were corrected assuming that the percent excess Parisian mortality for both sexes was the same in 1915 as in 1901–1905.</p

1914 French birth certificate.

<p>The birth certificate gives the date of birth, sex and parental occupations at the time of the birth (zone a). The date of death, if after March 29^th 1945, is available in the margin of the birth certificate (zone c). The dates of other life events (zone b) such as marriages and divorces are also notified by law in the margin (since 1897 for marriages, 1939 for divorces) and are used to classify those without a date of death. When no life event is notified after March 29^th 1945, the individual is considered dead before this date. Conversely, individuals without a date of death but known to be alive on March 29^th 1945 because of a life event after this date are considered alive at age 99. The birth certificate shown was registered on January 20^th 1915 and is held by the city hall of the 15^th arrondissement of Paris.</p

Additional file 1 of Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease

Additional file 1. Fig. S1. Scheme of the genomic map (5’) proximal from the CDH1 gene. Studied CpGs are figured as CGI, or as lollipops for the 1st enhancer. The rs16260 A/C variant is shown. Fig. S2. ROC curve testing the association between CD and the methylation at the CDH1 locus in ileal mucosa. A logistic regression explored the association between CD and the enhancer CpGs according to the methylation status of CGI. The coefficient of the latter adjustment variable was used to weigh the enhancer CpGs value based on the CGI methylation status. Fig. S3. Correlation of the methylation of the 1st enhancer studied CpGs in the mucosa of pooled CD and control patients. R (p value). Fig. S4: Correlation of the methylation of the 1st enhancer studied CpGs in PBMC of pooled CD and control patients. R (p-value). Fig. S5. Methylation of the 1st enhancer CpGs in (A) mucosa; (B) PBMC of patients with CD or controls, according to the methylation status of the CGI. No significant differences were detected. Table S1. Complete individual methylation data in the studied CD patients and controls. Table S2. Methylation in mucosa does not depend on rs16260 (C>A) genotype. However, we observed non-significant trend for increased CGI methylation in patients with CC genotype. No had AA genotype was present. Mean (±SD); decimal values rounded to the nearest integer

Analysis of the infectious environment of T1D in the Isis-Diab cohort compared with virtual controls.

<p>Red/ blue dots indicate that the patients were more/less exposed than the controls. The two lines stand for tests significance at the 0.05 level without (bottom line) and with (upper line) Bonferroni correction for multiple testing (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170658#pone.0170658.t002" target="_blank">Table 2</a> for the definition of INF-E variables).</p

SNPs found associated with an environmental exposure to infectious diseases.

<p>The SNPs listed are those for which the p-value of the final test was classified as « indicative » of a possible association (p<10⁻⁷, see Material and Methods). The 2 SNPs that survived the Bonferroni correction are indicated in bold.</p