
S1_Fig.tif
<div><p>The numbers stated are the number of identified independent loci for the respective analysis. Given in brackets is the number of the identified loci that are novel loci for the trait, i.e. have not been previously reported for association with the trait.</p>
</div>
10.1371/journal.pgen.1005378.s001

S2_Fig.tif
<div><p>QQ-plots for BMI (A) and WHR<sub>adjBMI</sub> (B) depicting overall association P-Values (red) and joint test P-Values (blue) for all SNPs and after excluding previously published BMI or WHR<sub>adjBMI</sub> associated regions (P<sub>Overall</sub>: magenta; P<sub>joint</sub>: cyan).</p>
</div>
10.1371/journal.pgen.1005378.s002

S3_Fig.tif
<div><p>Each plot highlights the most significant SNP for age-differences and illustrates p-values for age-differences (P<sub>agediff</sub>), sex-differences (P<sub>sexdiff</sub>), all strata combined (P<sub>Overall</sub>), and the joint test (P<sub>Joint</sub>). The figure is sorted according to <b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.t001" target="_blank">Table 1</a></b>. The plots are based on GrCh37 build positions and annotations.</p>
</div>
10.1371/journal.pgen.1005378.s003

S4_Fig.tif
10.1371/journal.pgen.1005378.s004

S5_Fig.tif
10.1371/journal.pgen.1005378.s005

S6_Fig.tif
<div><p>Each plot highlights the most significant SNP for sex-differences and illustrates p-values for age-differences (P<sub>agediff</sub>), sex-differences(P<sub>sexdiff</sub>), all strata combined (P<sub>Overall</sub>), and the joint test (P<sub>Joint</sub>). The figure is sorted according to <b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.t002" target="_blank">Table 2</a></b>. The plots are based on GrCh37 build positions and annotations.</p>
</div>
10.1371/journal.pgen.1005378.s006

S7_Fig.tif
10.1371/journal.pgen.1005378.s007

S8_Fig.tif
10.1371/journal.pgen.1005378.s008

S9_Fig.tif
<div><p>The figures illustrate the power of scanning P<sub>sexdiff</sub> (A: unfiltered, B: pre-filtered on P<sub>Overall</sub>), P<sub>agediff</sub> (C: unfiltered, D: pre-filtered on P<sub>Overall</sub>), and P<sub>agesexdiff</sub> (E: unfiltered, F: pre-filtered on P<sub>sexdiff</sub> or on P<sub>agediff</sub>). We assume four equally sized strata, a total sample size of N = 300,000 (comparable to the sample size in our BMI analyses). To investigate varying scenarios of interaction effects, we set (i) b<sub>F&lt;50y</sub> = 0.033, a median BMI effect near <i>MAP2K5</i> from Speliotes et al. (R<sup>2</sup> = 0.037%), (ii) b<sub>M&gt;50y</sub> = 0, and (iii) vary b<sub>F&gt;50y</sub> and b<sub>M&lt;50y</sub> on the x- and y-axes respectively.</p>
</div>
10.1371/journal.pgen.1005378.s009

S10_Fig.tif
<div><p>The figure shows the power to detect age-difference, sex-difference or age x sex-difference in at least one of our scans and for varying scenarios of effect size combinations between the 4 strata. We assume four equally sized strata and a total sample size of N = 300,000 (comparable to the sample size in our BMI analyses). Furthermore, for each plot we (i) set b<sub>F&lt;50y</sub> to a known BMI effect sizes from Speliotes et al. paper (using a small (<i>PTPB2)</i>, medium (<i>NEGR1</i>) and the largest (<i>FTO</i>) effect size), (ii) set b<sub>M&gt;50y</sub> = 0, and (iii) vary b<sub>F&gt;50y</sub> and b<sub>M&lt;50y</sub> on the axes.</p>
</div>
10.1371/journal.pgen.1005378.s010

S11_Fig.tif
<div><p>The figure shows the power to detect age-difference, sex-difference or age x sex-difference in at least one of our scans and for varying scenarios of effect size combinations between the 4 strata. We assume four equally sized strata and a total sample size of N = 200,000 (comparable to the sample size in our WHR<sub>adjBMI</sub> analyses). Furthermore, for each plot we (i) set b<sub>F&lt;50y</sub> to a known WHR<sub>adjBMI</sub> effect sizes from Heid et al. paper (using a small (<i>CPEB4)</i>, medium (<i>LYPLAL1</i>) and the largest (<i>RSPO3</i>) effect size), (ii) set b<sub>M&gt;50y</sub> = 0, and (iii) vary b<sub>F&gt;50y</sub> and b<sub>M&lt;50y</sub> on the axes.</p>
</div>
10.1371/journal.pgen.1005378.s011

S12_Fig.tif
<div><p>Loci are ordered according to trends in absolute magnitude of effect: 1) where the absolute magnitude of effect is largest in adolescent/youngest adults (ages 16–25y)<sup>1</sup>, 2) where absolute magnitude is largest in adults (&#8804;50y), and 3) where absolute magnitude is largest in older adults (&gt;50y). BMI: Body mass index; SE: standard error; Details for men and women ages 16&#8211;25 have been described elsewhere (Graff et al.: &#8220;Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.&#8221; Human Molecular Genetics 2013).</p>
</div>
10.1371/journal.pgen.1005378.s012

S13_Fig.tif
<div><p>WHR<sub>adjBMI</sub>: waist-to-hip ratio adjusted for body-mass index; eQTL: expression quantitative trait loci. Sex-specific associations were computed to identify cis eQTL signals that were likely to be coincident with the WHR<sub>adjBMI</sub> using human eQTL in lymphoblastoid cells.</p>
</div>
10.1371/journal.pgen.1005378.s013

S14_Fig.tif
10.1371/journal.pgen.1005378.s014

S15_Fig.tif
<div><p>Each plot highlights the most significant SNP for the combined effect (P<sub>Overall</sub>) or for the joint test (P<sub>Joint</sub>) and illustrates p-values for age-differences (P<sub>Agediff</sub>), sex-differences (P<sub>Sexdiff</sub>) and P<sub>Joint</sub> or P<sub>Overall</sub> respectively<sup>a</sup>. The figure is sorted according to chromosome and position. The plots are based on GrCh37 build positions and annotations. For three loci we identified two different SNPs that met the significance threshold for the scan of P<sub>Overall</sub> and P<sub>Joint</sub>. For each set we plotted the SNP with the lowest P-value based on the scan it was identified for. These loci and the SNP plotted are as follows: 1) rs7421089 &#8722; Selected for PJoint and rs10804189 &#8722; Selected for POverall-&gt;rs10804189 is plotted, 2) rs1557765 &#8722; Selected for POverall and rs7928810 &#8722; Selected for PJoint-&gt; rs7928810 is plotted, and 3) rs11181001&#8722; Selected for PJoint &amp; rs1405552&#8722; Selected for POverall-&gt; rs1405552 is plotted.</p>
</div>
10.1371/journal.pgen.1005378.s015

S16_Fig.tif
<div><p>Each plot highlights the most significant SNP for the combined effect (P<sub>Overall</sub>) or for the joint test (P<sub>Joint</sub>) and illustrates p-values for age-differences (P<sub>Agediff</sub>), sex-differences (P<sub>Sexdiff</sub>) and P<sub>Joint</sub> or P<sub>Overall</sub> respectively. The figure is sorted according to chromosome and position. The plots are based on GrCh37 build positions and annotations.</p>
</div>
10.1371/journal.pgen.1005378.s016

S1_Table.xlsx
10.1371/journal.pgen.1005378.s017

S2_Table.xlsx
10.1371/journal.pgen.1005378.s018

S3_Table.xlsx
<div><p>** There were significant differences in the number of subjects available for different phenotypes. In this case, separate summary statistics were provided.</p>
</div>
10.1371/journal.pgen.1005378.s019

S4_Table.xlsx
<div><p>The table is ordered according to <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.t001" target="_blank">Table 1</a>.</p>
</div>
10.1371/journal.pgen.1005378.s020

S5_Table.xlsx
<div><p>The table is ordered according to <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005378#pgen.1005378.t002" target="_blank">Table 2</a>.</p>
</div>
10.1371/journal.pgen.1005378.s021

S6_Table.xlsx
<div><p>Abbreviations: Effect Allele (EA), Other Allele (OA), SNP-by-age interaction effect (b<sub>SNPxAGE</sub>), SNP-by-age interaction effect standard error (SE<sub>SNPxAGE</sub>), SNP-by-age interaction P-value (P<sub>SNPxAGE</sub>).</p>
</div>
10.1371/journal.pgen.1005378.s022

S7_Table.xlsx
<div><p>Abbreviations: Effect Alelle (EA), Other Allele (OA), High Density Lipoprotein Cholesterol (HDL), Low Density Lipoprotein (LDL), Total Cholesterol (TC), Triglycerides (TG).</p>
</div>
10.1371/journal.pgen.1005378.s023

S8_Table.xlsx
<div><p>Abbreviations: Effect Allele (EA), Other Allele (OA), Odds Ratio (OR).</p>
</div>
10.1371/journal.pgen.1005378.s024

S9_Table.xlsx
<div><p>Abbreviations: Effect Allele (EA), Other Allele (OA), Odds Ratio (OR).</p>
</div>
10.1371/journal.pgen.1005378.s025

S10_Table.xlsx
<div><p>The table shows SNPs that meet a Bonferroni-corrected significance level (&lt;0.05/44) for its sex-specific association with the lookup trait and no association with the lookup trait in the other sex. Only women-specific loci displayed similar patterns in the look-up data. None of the opposite effect direction loci showed opposite effects (requesting P&lt;0.05 in both sexes) with a look-up trait.</p>
</div>
10.1371/journal.pgen.1005378.s026

S11_Table.xlsx
10.1371/journal.pgen.1005378.s027

S12_Table.xlsx
10.1371/journal.pgen.1005378.s028

S13_Table.xlsx
<div><p>Analysis was restricted to non-case control studies.</p>
</div>
10.1371/journal.pgen.1005378.s029

S14_Table.xlsx
<div><p>Analysis was restricted to non-case control studies.</p>
</div>
10.1371/journal.pgen.1005378.s030

S15_Table.xlsx
10.1371/journal.pgen.1005378.s031

S16_Table.xlsx
10.1371/journal.pgen.1005378.s032

S17_Table.xlsx
10.1371/journal.pgen.1005378.s033

S18_Table.xlsx
10.1371/journal.pgen.1005378.s034

S19_Table.xlsx
<div><p>Presented are SNPs with significant sex-differences in eQTL effects, selected according to FDR(P-Sexdiff) &lt; 5%, with and without initial filtering on overall expression effects (FDR(P-Overall) &lt; 20%).</p>
</div>
10.1371/journal.pgen.1005378.s035

S20_Table.xlsx
10.1371/journal.pgen.1005378.s036

S21_Table.xlsx
10.1371/journal.pgen.1005378.s037

S22_Table.xlsx
<div><p>Functions that remain significant after B-H (p&lt;0.05) correction are marked in bold.</p>
</div>
10.1371/journal.pgen.1005378.s038

S23_Table.xlsx
<div><p>Functions that remain significant after B-H correction are marked in bold.</p>
</div>
10.1371/journal.pgen.1005378.s039

S24_Table.xlsx
<div><p>Pathways that remain significant after B-H correction are marked in bold.</p>
</div>
10.1371/journal.pgen.1005378.s040

S25_Table.xlsx
<div><p>Functions that remain significant after B-H correction are marked in bold.</p>
</div>
10.1371/journal.pgen.1005378.s041

S26_Table.xlsx
<div><p>Functions that remain significant after B-H correction are marked in bold.</p>
</div>
10.1371/journal.pgen.1005378.s042

S27_Table.xlsx
10.1371/journal.pgen.1005378.s043

S28_Table.xlsx
10.1371/journal.pgen.1005378.s044

S29_Table.xlsx
10.1371/journal.pgen.1005378.s045

S1_Text.docx
10.1371/journal.pgen.1005378.s046

S2_Text.docx
10.1371/journal.pgen.1005378.s047
