Results for selected top interactions among top marginal loci with p-value less than 5×10⁻⁵ in Phase I studies.

<p>P_het is the heterogeneity p-value.</p

Forest plot for meta-analysis results of GxG between rs1571218 and rs10879357.

<p>Box sizes are proportional to the inverse variance for each study and the lines depict the confidence intervals. The diamonds represent the fixed effects meta-analysis results, with the width of the diamond representing the confidence interval. The results of two advanced adenoma studies (HPFS Adv Adnm and NHS Adv Adnm) are shown at the bottom but not incorporated in the meta-analysis.</p

An illustration of different two-SNP interaction models. SNP 1 has genotype AA, Aa and aa; SNP 2 has genotype BB, Bb, and bb. A and B are the major alleles for SNP1 and 2, respectively.

<p>Each entry in the tables represents the risk of the corresponding genotype combination relative to the baseline (AA/BB). (a) Multiplicative interaction model; (b) Unrestricted interaction model; (c) Average Risk Due to Interaction (ARDI) model.</p

Studies in Genetics and Epidemiology Colorectal Cancer Consortium (GECCO).

a<p>Sample size excludes overlap with CCFR;</p>†<p>Sample sizes given only for subjects clustering with HapMap CEU population in PCA (for data that has undergone QC);</p>¶<p>Includes participants with data downloaded from dbGaP prostate and lung studies;*for adenoma, number and % colon does not include subjects with adenomas located in both colon and rectum.</p

Regional interaction association plot for interacting region 5q21 with known CRC locus rs10795668.

<p>The left y-axis shows the -log10 of the meta-analysis interaction p value. The right y-axis shows the recombination rate. Each dot on the plot represents the result for one SNP. The diamond dot represents SNP rs367615 and the round dots represent other SNPs. Difference colors of SNPs indicate different LD strength between the corresponding SNP and rs367615, measured by r². The bottom of the figure shows the genes in the plotted region.</p

Interaction pattern between rs10795668 and rs367615.

<p>Interaction pattern between rs10795668 and rs367615.</p

Forest plot for meta-analysis results of GxG between rs10795668 and rs367615.

<p>Box sizes are proportional to the inverse variance for each study and the lines depict the confidence intervals. The diamonds represent the fixed effects meta-analysis results, with the width of the diamond representing the confidence interval. The results of two advanced adenoma studies (HPFS Adv Adnm and NHS Adv Adnm) are shown at the bottom but not incorporated in the meta-analysis.</p

Results for selected top interactions for known CRC loci with p-value less than 10⁻⁶ in Phase I studies.

*<p>P_het is the heterogeneity p-value.</p

The association between CRC and smoking (ever vs. never smokers [a]; pack-years of smoking [b]).

<p>Never smokers were assigned the value 0 for pack-years of smoking. OR: odds ratio; OR for pack-years of smoking is based on per 20 pack-years increase. Age, sex (if applicable), and study site (if applicable) were adjusted in model. ASTERISK: The French Association STudy Evaluating RISK for sporadic colorectal cancer; CCFR: Colon Cancer Family Registry; Colon23: Hawaii Colorectal Cancer Studies 2 and 3.; DACHS: Darmkrebs: Chancen der Verhütung durch Screening; DALS: Diet, Activity and Lifestyle Study; HPFS:Health Professionals Follow-up Study; HPFS_AD: Health Professionals Follow-up Study for colorectal adenoma; MEC: Multiethnic Cohort Study; NHS: Nurses’ Health Study; NHS_AD: Nurses’ Health Study for colorectal adenoma; OFCCR: Ontario Familial Colorectal Cancer Registry; PMH-CCFR: Postmenopausal Hormone study- Colon Cancer Family Registry; PLCO: Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; VITAL: VITamins And Lifestyle; WHI: Women’s Health Initiative. CCFR is a collaborating study with GECCO. smk_ever: ever smokers; smk_pkyr20: pack-years of smoking; het.pval: p value of heterogeneity.</p

Forest plot for meta-analysis of interaction analysis for rs9409565 and light-to-moderate drinking among men (a), women (b) and combined (c).

<p>Odds ratios (ORs) and 95% confidence intervals (95% CI) are presented for the multiplicative interaction between each additional copy of the count (or tested) allele (C) and light-to-moderate vs. non/occasional drinkers. The box sizes are proportional in size to the inverse of the variance for each study, and the lines visually depict the confidence interval. Results from the fixed-effects meta-analysis are shown as diamonds. The width of the diamond represents the confidence interval. P value of heterogeneity for (a), (b), and (c) is 0.93, 0.78, and 0.96, respectively.</p