Distribution of characteristics of the study population (n = 3,000) by PTSD status.

<p><i>Distributions are presented as means ± standard deviation for continuous, p values from χ² test or F test for association with PTSD,</i></p>*<p><i>only n = 2,528.</i></p

Association of PTSD with telomere length estimated by linear regression.

<p><i>1) Model 1 was adjusted for age, sex and BMI.</i></p><p><i>2) Model 2 was adjusted for age, sex and additionally for smoking status, alcohol consumption, physical inactivity, actual hypertension, TC/HDL and history of chronic diseases.</i></p><p><i>R²: 0.187 (model 1), 0.188 (model 2).</i></p

Mean telomere length of study participants, stratified by PTSD status and adjusted for age, sex, BMI, smoking status, alcohol consumption, physical inactivity, actual hypertension, TC/HDL-C and history of chronic diseases.

<p><i>Vertical reference line denotes mean TL for no PTSD</i>.</p

Association between JCA antibody response and markers in the Human Leuococyte region on chromosome 6.

<p><b>A</b> Plot of the <i>HLA</i> region from the meta-analysis (random effects model) of the association between GWAS markers and JCV serostatus in the Scandinavian (n = 634) and German (n = 718) MS cases and the Swedish controls (n = 465) on chromosome 6. The horizontal line represent a p-values of and 1×10⁻⁸. All analyses were adjusted for gender, age at sampling, and principal components. The most significant SNP is rs34454237 (p<4×10⁻¹⁴) which maps 42.6 kb from the <i>HLA-DRB1</i> gene towards the HLA class I genes. <b>B</b> Plot of the <i>HLA</i> region from the meta-analysis (random effects model) of the association between GWAS markers and transformed anti-JCV nOD levels in the anti-JCV antibody positive Scandinavian (n = 374) and German (n = 294) MS cases and the Swedish controls (n = 406). The horizontal lines represent a p-value of and 1×10⁻⁸. All analyses adjusted for gender, age at sampling, and principal components. The locations of the <i>HLA-A</i>, <i>-C</i>, <i>-B</i>, <i>-DRB1</i>, <i>-DQA1</i> and -<i>DRB1</i> loci are noted using genome build 36. The most significant SNP is rs3129860 (p<1×10⁻⁷) which maps 145.7 kb from the <i>HLA-DRB1</i> gene in the direction of the <i>HLA</i> class I genes.</p

<i>HLA</i>-association to transformed JCV nOD levels in Scandinavian cohort.

<p>Results from the linear regression analysis of the association between HLA-alleles and JCV nOD levels. Only alleles that are nominally significant (p<0.05) alleles in any cohort in this or <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat-1004084-t005" target="_blank">table 5</a> are presented. P-values that reach nominal significance, 0.05 are marked in bold. The median nOD levels are given among individuals positive or negative for respective <i>HLA</i> allele. In the crude analysis each allele was analysed on its own, adjusted for gender and age. Age at sampling was divided into four categories, 18–29, 30–39, 40–49, and 50 and older, with group 40–49 as the reference. The analysis was performed in R version 2.15.1 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-R1" target="_blank">[50]</a>. *Multivariate: all nominally significant alleles from the same gene in the same model, adjusted for age and gender. † Median nOD is given among individuals positive or negative for respective <i>HLA</i> allele.</p><p>Common extended HLA haplotypes were selected from those published in the literature for the Caucasian population <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-Askar1" target="_blank">[19]</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-Alper1" target="_blank">[21]</a>. Alternative common <i>DRB1*15</i> haplotypes <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*02</i>, <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*03</i>, <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*02</i>, <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*11</i>. The <i>DQB1*03:01-DQA1*05-DRB1*11-B*51-A*02</i> haplotype exist with many different C alleles, <i>C*05</i> not being the most common one.</p

Analysis of association between <i>HLA</i> genotypes and anti-JCV antibody status in joint analysis of Swedish controls, Scandinavian and German MS patients.

<p><b>A</b> Odds ratio (OR) for <i>DRB1</i> alleles and genotypes from logistic regression analyses performed in R version 2.15.1 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-R1" target="_blank">[50]</a>. The analyses were adjusted for gender, cohort (Swedish controls, Scandinavian MS patients or German MS patients) and age at sampling. Age at sampling was divided into four categories, 18–29, 30–39, 40–49, and 50 and older, with group 40–49 as the reference. Error bars represents 95% confidence intervals. OR below 1 are plotted as −1/OR. Grey indicates associations with p<0.05, white p>0.05. <b>B</b> Odds ratio (OR) for <i>DRB1</i> alleles and genotypes from logistic regression analyses performed in R version 2.15.1 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-R1" target="_blank">[50]</a>. The analyses were adjusted for gender, cohort (Swedish controls, Scandinavian MS patients or German MS patients) and age at sampling. Age at sampling was divided into four categories, 18–29, 30–39, 40–49, and 50 and older, with group 40–49 as the reference. Error bars represents 95% confidence intervals. OR below 1 are plotted as −1/OR. Grey indicates associations with p<0.05, white p>0.05. <i>DQA1*01:03</i> homozygotes are not included as this combination was so rare (0.4%).</p

<i>HLA</i>-associations to anti-JCV antibody status in Scandinavian cohort.

<p>Results from the association analysis between <i>HLA</i>-alleles and JCV seropositivity in the Scandinavian MS cases and the Swedish controls. The frequencies in the second column are the frequencies of <i>HLA</i> alleles among JCV Ab seropositive and seronegative respectively. In the crude analysis each allele was analysed on its own, adjusted for gender and age. The analysis was performed in in R version 2.15.1 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-R1" target="_blank">[50]</a>. The analysis was adjusted for age at sampling and gender. Age at sampling was divided into four categories, 18–29, 30–39, 40–49, and 50 and older, with group 40–49 as the reference. *Multivariate: all nominally significant alleles from the same gene in the same model, adjusted for age and gender.</p><p>Common extended <i>HLA</i> haplotypes were selected from those published in the literature for the Caucasian population <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-Askar1" target="_blank">[19]</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-Alper1" target="_blank">[21]</a>. Alternative common DRB1*15 haplotypes <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*02</i>, <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*03</i>, <i>DQB1*06:02-DQA1*01:02-DQB1*15-B*51-C*?-A*02</i>, <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*11</i>. The <i>DQB1*03:01-DQA1*05-DRB1*11-B*51-A*02</i> haplotype exist with many different C alleles, <i>C*05</i> not being the most common one.</p

Demographic information.

<p>Demographic information on 1621 Scandinavian MS cases, 1064 Swedish controls and 718 German MS cases with anti-JCV antibody status, anti-JCV nOD antibody levels and HLA-genotypes (from either <i>HLA-A</i>, <i>B</i>, <i>C</i>, <i>DRB1</i>, <i>DQB1</i>, or <i>DQA1</i>). *Since all individuals were GWAS genotyped, they had genotype information for all <i>HLA</i>-loci, the numbers shown are the number that passed the quality score ≥0.70 for both alleles for imputed <i>HLA</i> genotypes.</p

<i>HLA</i>-association to transformed JCV nOD levels in German MS patients.

<p>Results from the linear regression analysis of the association between <i>HLA</i>-alleles and JCV nOD levels. Only alleles that are nominally significant (p<0.05) alleles in any cohort in this or <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat-1004084-t004" target="_blank">table 4</a> are presented. P-values that reach nominal significance, 0.05 are marked in bold. The median nOD levels are given among individuals positive or negative for respective HLA allele. Each allele was analysed on its own, adjusted for age at sampling, significant principal components from EIGENSTRAT analysis of genomewide SNP data and gender. Age was included as a continuous covariate. The analysis was carried out in PLINK 1.07 <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-Purcell1" target="_blank">[49]</a>. As only alleles on the <i>DQB1*06:02-DQA1*01:02-DRB1*15</i> haplotype were significant no multivariate analysis was performed. * Median nOD is given among individuals positive or negative for respective <i>HLA</i> allele.</p><p>Common extended HLA haplotypes were selected from those published in the literature for the Caucasian population <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-Askar1" target="_blank">[19]</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004084#ppat.1004084-Alper1" target="_blank">[21]</a>. Alternative common <i>DRB1*15</i> haplotypes <i>DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*02, DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*03, DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*02, DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*11. The DQB1*03:01-DQA1*05-DRB1*11-B*51-A*02</i> haplotype exist with many different C alleles, <i>C*05</i> not being the most common one.</p

Forest plot of meta-analyzed results for the effect per minor allele of rs3748312 on FEV1 in ever-smokers, adjusted for sex, age, height, population stratification factors and the presence of PI S and Z alleles.

<p>Studies based on population isolates with a high degree of cryptic relatedness are presented separately. Effect estimates of meta-analyses are shown with green diamonds. I² is a measure of the heterogeneity between studies. Random effect meta-analyses are included if I²>0.5. Study weights (blue squares) correspond to fixed effect meta-analyses.</p