Fig. 2.

Germline variants influencing primary tumor type. A) Ideogram of all loci associated with a single tumor type (blue triangles). Red triangles indicate an association with the specific somatic alteration of a cancer gene. B) Manhattan (LocusZoom) plot (78) displaying markers at 8q24.13 associated with incidence of breast cancer. Markers are colored according to linkage disequilibrium (r² values) derived from the 1000 Genomes European samples. C) Markers at 8q24.13 also associated with age of diagnosis with breast cancer. A/A indicates individuals homozygous for the major allele and A/a, a/a indicate individuals with one or more copies of the minor allele. D) Quantile-quantile plot showing the observed p-values of association (versus random expectation) for 557 loci associated with cancer risk in previous studies. The substantial elevation above the diagonal (red) indicates support for many of these previous loci in the present TCGA analysis. E) Manhattan plot displaying markers at 9q22.23 associated with thyroid carcinoma and genes encoded within that region. Colored genes were found to have altered expression in Thyroid tumors in the presence of the minor allele. F) Mean expression of genes highlighted in panel (E) versus the number of minor alleles. Bars show standard error on mean estimates.