Number of significant pathway associations (using FDR< = 0.05) for Central Europe-Toronto (CETO) and Germany-MD Anderson (GRMD) by pathway analysis method.

<p>Number of significant pathway associations (using FDR< = 0.05) for Central Europe-Toronto (CETO) and Germany-MD Anderson (GRMD) by pathway analysis method.</p

Comparison of odds ratios for acetylcholine receptor pathway showing.

<p>A) the most significant SNP for each gene used in Central Europe-Toronto analysis and odds ratios for same SNPs for Germany MD Anderson); B) the most significant SNP assigned to each gene in either data set (i.e., the actual SNPs used in pathway analyses in the two data sets). Chromosome number (Chr) and genes for both graphs are shown on left. (Central Europe – Toronto SNPs: solid fill, Germany MD Anderson matching SNPs: no fill; Germany MD Anderson top SNP (differing from Central Europe-Toronto): grey fill). A) Reference allele same in both Central Europe-Toronto and Germany-MD Anderson but chosen to show positive association for Central Europe-Toronto. B) Reference allele always chosen to show positive association. <i>CHRNA5</i> is excluded as SNPs are identical to those representing <i>CHRNA3</i>. Odds ratios adjusted for age, sex and country of study.</p

Comparison of study designs, selected epidemiologic variables, genotyping platforms and results.

†<p>After implementing data quality measures described in methods.</p

Comparison of FDRs (top line) and P-values (in brackets) for Central Europe-Toronto (CETO) and Germany-MD Anderson (GRMD) for top lung cancer risk associated pathways identified by different analysis methods using GO level 4 pathways.

<p>Bold: significant after adjustment for multiple comparisons (FDR≤0.05) in both CETO and GRMD.</p><p>Bold with italics: significant after adjustment for multiple comparisons in one data set (FDR≤0.05), nominal significance in other (P≤0.05).</p><p><u>Underline</u>: Top pathways identified by more than one pathway analysis method within a data set.</p>†<p>Abbreviated GO category name. Full category names as follows: Ras-GEF: Ras guanyl-nucleotide exchange factor; LDL binding: low-density lipoprotein binding; acetylcholine receptor: acetylcholine receptor activity; immune response: adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains; complement activation: complement activation, classical pathway; somatic recombination: somatic recombination of immunoglobulin gene segments; peptide receptor: G-protein coupled peptide receptor activity; positive reg phosphorous: positive regulation of phosphorus metabolic process; antigen processing: antigen processing and presentation of peptide antigen via MHC Class I; retrograde transport, GER: Retrograde vesicle mediated transport, golgi to endoplasmic reticulum.</p>‡<p>Significant based on Benjamini-Hochberg FDR calculation.</p

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

Seven SNPs show sex difference.

a<p>Trait and sex for which the SNP was selected;</p>b<p>Gene labels state the nearest gene or the gene as published previously; details on all genes near the association signal can be found in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500.s002" target="_blank">Figure S2</a>;</p>c<p>One-sided P-Values.</p>d<p>larger sample size due to one additional study that did not have hip circumference, and therefore could not contribute to WHRadjBMI.</p>e<p>smaller sample size as this SNP was not on Metabochip.</p><p>Shown are the seven SNPs with significant (at 5% false discovery rate) sex difference in the follow-up data. These seven SNPs exhibit genome-wide significant association in women (joint discovery and follow-up <i>P_women</i><5×10−8) and only two of these show nominally significant association in men (joint <i>P_men</i><0.05). The three loci MAP3K1, HSD17B4, and PPARG are shown here for the first time for their anthropometric trait association as well as for sex-difference.</p

Consistently higher effect sizes for women for all seven loci.

<p>Shown are beta-estimates and 95% confidence intervals for the seven identified SNPs (also stating the phenotype for which the SNP was selected for).</p

Overview of design and findings.

<p>Among the 7 identified loci, we defined those close to (<1 cM) published hits <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500-LangoAllen1" target="_blank">[25]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500-Speliotes1" target="_blank">[29]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500-Heid1" target="_blank">[31]</a> as <i>near published hit</i>s and <i>novel</i> otherwise. Novel loci with sex-combined discovery P-value<5.8×10⁻⁵, which is the P-value cut-off corresponding to 5% FDR, were declared as loci that <i>could have been discovered also with sex-combined analysis</i>, and otherwise that these <i>would have been missed without the sex-stratified analyses</i>. FDR = false discovery rate.</p