Overlap of lymphoma risk SNPs with regulatory regions in GM12878.

<p>The histograms represent the distribution of how many random loci overlap a specific annotation. The blue represents the mean of the empirical null distribution while the red line represents the real number of loci from the lymphoma and CLL GWAS that overlap the specific regulatory annotation. A, Overlap of SNPs with DNase hypersensitivity regions in GM12878. B, Overlap of SNPs with active promoters and strong enhancers as annotated by ChromHMM in GM12878. C, Overlap of SNPs with active promoters and strong enhancers as annotated by Segway in GM12878.</p

Enrichment of lymphoma and CLL risk SNPs in DNase-hypersensitive sites of lymphoblastoid cell lines.

<p>(A-I) These histograms represent the distribution of how many random loci overlap a specific annotation. The blue represents the mean of the empirical null distribution while the red line represents the real number of loci from the lymphoma and CLL GWAS that overlap the DNase hypersensitive site in the specified cell line: (A) GM19238 (B) GM19240 (C) GM12864 (D) GM12865 (E) GM06990 (F) GM19239 (G) GM18507 (H) GM12892 (I) GM12891. (J) Th0 (K) CD20+ (L) Summary of distribution of tissue of origin for cell lines in which lymphoma and CLL risk SNPs are either enriched (p<0.0004) in DNase hypersensitive sites or not enriched.</p

UES algorithm visualization.

<p>This represents the generalized workflow to determine the SNP enrichment in an ENCODE track. A full description and details of the algorithm can be found in the Materials and Methods.</p

Novel loci achieving genome-wide significance (P<5x10^-8) in meta-analyses for PA-adjusted SNP main effect (P_adjPA) or the joint test of SNP main effect and SNP-PA interaction (P_joint).

<p>Novel loci achieving genome-wide significance (P<5x10^-8) in meta-analyses for PA-adjusted SNP main effect (P_adjPA) or the joint test of SNP main effect and SNP-PA interaction (P_joint).</p

Genes of biological interest within 500 kb of lead SNPs associated with WC_adjBMI or WHR_adjBMI.

<p>Genes of biological interest within 500 kb of lead SNPs associated with WC_adjBMI or WHR_adjBMI.</p

Genes of biological interest within 500 kb of lead SNPs associated with BMI.

<p>Genes of biological interest within 500 kb of lead SNPs associated with BMI.</p

Power to identify PA-adjusted main, joint or GxPA interaction effects in 200,000 individuals (45,000 inactive, 155,000 active).

<p>The plots compare power to identify genome-wide significant main effects (P_adjPA<5x10^-8, dashed black), joint effects (P_JOINT<5x10^-8, dotted green) or GxPA interaction effects (P_INT<5x10^-8, solid magenta) as well as the power to identify Bonferroni-corrected interaction effects (P_INT<0.05/number of loci, solid orange) for the SNPs that reached a genome-wide significant PA-adjusted main effect association (P_adjPA<5x10^-8). The power computations were based on analytical power formulae provided elsewhere [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006528#pgen.1006528.ref050" target="_blank">50</a>] and were conducted a-priori based on various types of known realistic BMI effect sizes [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006528#pgen.1006528.ref051" target="_blank">51</a>]. <b>Panels A, C, E</b>: Assuming an effect in inactive individuals similar to a small (, comparable to the known BMI effect of the <i>NUDT3</i> locus), medium (, comparable to the known BMI effect of the <i>BDNF</i> locus) and large (, comparable to the known BMI effect of the <i>FTO</i> locus) realistic effect on BMI and for various effects in physically active individuals (varied on the x axis); <b>Panels B,D,F</b>: Assuming an effect in physically active individuals similar to the small, medium and large realistic effects of the <i>NUDT3</i>, <i>BDNF and FTO</i> loci on BMI and for various effects in inactive individuals (varied on x axis).</p