Additional file 1: of GWASeq: targeted re-sequencing follow up to GWAS

Boxplot of per-sample coverage by region, for each of the sequenced regions, by case–control status. (TIFF 8219 kb

Additional file 2: of GWASeq: targeted re-sequencing follow up to GWAS

Regional plots of associations for each targeted region. rs numbers and purple circles indicate the focal GWAS SNP that the region was selected around. Colored circles indicate degree of LD among SNPs. Grey circles indicate novel SNPs that lack LD information based on the 2012 release of the 1000 Genomes data. The rs number at figure top is centered around the location of the focal SNP. (ZIP 1921 kb

Genome-wide Linkage Scans of White pMMR Family Groups with HLOD Score>3.0.

<p>HLOD scores from genome-wide linkage scan of five white pMMR family subgroups. The blue line represents HLODs under the dominant model and the red line represents the HLODs under the recessive model. Maximum observed HLODs>3.0 (in parenthesis) are labeled with the nearest SNP in four regions. (A) Family mean age at diagnosis <50 years (N = 58). (B) All families (N = 356). (C) Families with four or more affected members (N = 67). (D) Clinic-based families (N = 88). (E) Families with two affected members (N = 200).</p

Summary of Colorectal Cancer Linkage Results with Maximum Observed HLOD Scores between 2.0 and 3.0.

a<p>Genotyped SNP nearest to the peak of the linkage region; distances are reported based on the NCBI build 36.2 and Haldane cM.</p>b<p>SNP location and the distance in bp is given in regards to the nearest gene.</p>c<p>Ascertainment method not reported.</p>d<p>Pseudo-gene.</p

Characteristics of 356 White Colorectal Cancer Families with No Evidence of Defective Mismatch Repair, N (%).

a<p>Ascertainment method not reported.</p>b<p>Microsatellite stability of the tumor; MSS indicates that the tumor was microsatellite stable; MSI-L indicates that the tumor had low microsatellite instability; Unknown indicates that the tumor stability status was not available.</p>c<p>Mismatch repair status of the tumor by immunohistochemical analysis; No loss indicates that the tumor showed complete presence of protein expression of all the MMR genes tested (MLH1, MSH2, MSH6, and PMS2); Unknown indicates that the tumor MMR-expression status was not available.</p>d<p>Unknown for both MSI and IHC on 67 families is due to not being tested but had a LOD<0.04 within 20 kb surrounding <i>MSH2</i>, <i>MLH1</i>, <i>MSH6</i>, <i>PMS2</i>, <i>PMS1</i>, <i>MSH3</i>, or <i>MLH3</i>.</p

The overlap in the distribution of family groups.

<p>The overlap in the distribution of family groups.</p

Summary of Colorectal Cancer Linkage Results with HLOD Scores>3.0.

a<p>Genotyped SNP nearest to the peak of the linkage region; distances are reported in bp based on the NCBI build 36.2 and Haldane cM.</p>b<p>Pseudo-gene.</p>c<p>Non-parametric Kong & Cox LOD.</p

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

Interaction pattern between rs10795668 and rs367615.

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