Association of variants in small GTPase genes with epithelial ovarian cancer risk (p-value<10⁻⁴) and functional annotation.

<p>Association of variants in small GTPase genes with epithelial ovarian cancer risk (p-value<10⁻⁴) and functional annotation.</p

Association of rs2256787 in the <i>ARHGEF10L</i> gene with invasive endometrioid EOC risk by study site and combined.

<p>Squares represent the estimated per-allele odds ratio (OR) and are proportional to sample size for each study; lines indicate its 95% confidence interval (CI); source indicates contributing study;[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0197561#pone.0197561.ref011" target="_blank">11</a>] MAF, control minor allele frequency; PVal, per-allele p-value adjusted for age, site, and principal components to account for residual differences in European ancestry.</p

Top SNPs associated with SER EOC across racial groups.

<p>¹ MAF, minor allele and its frequency</p><p>² p-value <0.05 are in bold</p><p>³ Odds ratio, 95% confidence interval</p><p>Top SNPs associated with SER EOC across racial groups.</p

The most significant SNPs in the transport pathway genes and risk of EOC by histology, invasiveness, and race/ethnicity¹.

<p>¹ INV: all invasive EOC combined; LMP: low malignant potential / borderline tumors; SER: serous; CC: clear cell; End: endometrioid; Muc: mucinous. Statistically significant associations are indicated in bold (P<0.05). Data format is the following: OR (95% CI); p-value; FDR q-value (white-European women). Only significant FDRs (q<0.2) are shown (<i>HEPH</i>: INV and SER<i>; UGT1A</i>: End).</p><p>The most significant SNPs in the transport pathway genes and risk of EOC by histology, invasiveness, and race/ethnicity<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128106#t001fn001" target="_blank">¹</a>.</p

Age-dependent BMI loci.

<p>Effect estimates (beta ±95CI) per standard deviation in BMI and risk allele for loci showing age-differences in men & women ≤50y compared to men & women >50y. Loci are ordered by greater magnitude of effect in men & women ≤50y compared to men & women >50y. (95%CI: 95% confidence interval; BMI: body mass index; SD: standard deviation, *Newly identified loci).</p

Forty-four WHR_adjBMI loci showing significant sex-differences.

<p>Chr: Chromosome; Pos: position; EAF: Effect Allele Frequency; EA: Effect allele; OA: Other allele</p><p>^a ‘Yes’ if the locus is mentioned as WHR_adjBMI locus for the first time</p><p>^b ‘Yes’ if the sex-difference in the effect on WHR_adjBMI is reported for the first time</p><p>^c Effect allele is according to the WHR_adjBMI increasing allele according to the associated sex.</p><p>The table shows the sex-specific (age-group combined) results, ordered by largest, positive effect in women to largest, negative effect in women. The age- and sex-specific results (four strata), more detailed information on the loci and on the screens for which they were detected are given in <b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.s021" target="_blank">S5 Table</a></b>.</p

Fifteen BMI loci showing significant age-differences in adults ≤50y compared to adults >50y.

<p>Chr: Chromosome; Pos: position; EAF: Effect Allele Frequency; EA: Effect allele; OA: Other allele</p><p>^a ‘Yes’ if the locus is mentioned as BMI locus for the first time</p><p>^b Effect allele is according to the BMI increasing allele according to the associated sex.</p><p>The table shows the age-group specific (sex-combined) results, ordered by largest to smallest effect in adults ≤50y. All loci were detected by the screen on age-difference that included the a-priori filter on <i>P</i>_{<i>Overall</i>} < 10⁻⁵. The age- and sex-specific results (four strata) and more detailed information on the loci are given in <b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.s020" target="_blank">S4 Table</a></b>.</p

Power heatplots.

<p>Power for the combination of screens and gain through a priori filtering for varying configurations of effect sizes across the 4 strata. The figures illustrate (A) the power to detect age-difference, sex-difference or age-sex-difference in at least one of our scans (on <i>P</i>_{<i>agediff</i>}, <i>P</i>_{<i>sexdiff</i>} and <i>P</i>_{<i>agesexdiff</i>}, with and without a priori filtering); and (B) a power comparison, comparing approaches with and without a priori filtering on <i>P</i>_{<i>Overall</i>} < 1x10^-5. We here assume four equally sized strata and a total sample size of N = 300,000 (comparable to the sample size in our BMI analyses). We set b_F≤50y = 0.033 (corresponding to a known and mean BMI effect in <i>MAP2K5</i> region with R² = 0.037%), b_M>50y = 0, and vary b_F>50y and b_M≤50 on the axes. This strategy allows us to cover the most interesting and plausible interaction effects: Two-way interactions, such as (i) pure age-difference (b_≤50y = 0.033, b_>50y = 0) and (ii) pure sex-difference (b_F = 0.033, b_M = 0); and three-way interactions, such as (iii) extreme three-way interaction with opposite direction across AGE and SEX, (iv) 1-strata interaction (b_F≤50y = 0.033, b_F>50y = b_M≤50y = b_M>50y = 0), and (v) 3-strata interaction (b_F≤50y = b_F>50y = b_M≤50y = 0.033, b_M>50y = 0).</p

Interaction QQ plots.

<p>Quantile-Quantile plots showing P-Values for age-difference (<i>P</i>_{<i>agediff</i>}, green), sex-difference (<i>P</i>_{<i>sexdiff</i>}, blue) and age- and sex-difference (<i>P</i>_{<i>agesexdiff</i>}, purple). For BMI the P-Values are depicted for all SNPs genome-wide (A) as well as for a limited subset of SNPs that survived pre-filtering on the overall association with BMI, <i>P</i>_{<i>Overall</i>} < 1x10^-5 (B). For WHR_adjBMI the P-Values are depicted for all SNPs genome-wide (C) as well as for a limited subset of SNPs that survived pre-filtering on the overall association with WHR_adjBMI, <i>P</i>_{<i>Overall</i>} < 1x10^-5 (D).</p

Sex-dependent WHR_adjBMI loci.

<p>Effect estimates (beta ± 95CI) per standard deviation in WHR_adjBMI and risk allele for loci showing sex-differences in women compared to men. Loci are ordered by greater magnitude of effect in women compared to men. (95%CI: 95% confidence interval; SD: standard deviation. *Newly identified loci. † Newly identified sex-differences)</p