Extended Data Fig. 4: mRNA expression of thyroid cancer-associated genes in normal thyroid tissue and thyroid cancer.

Genes were identified from ANNOVAR annotations of genome-wide significant variants in thyroid cancer GWAS meta-analysis and FUSION TWAS cis-eQTL analysis. The dark blue color indicates genes with high expression in normal thyroid tissue, where the thyroid is among the top three tissues with the highest expression in pan-tissue transcriptome analysis from the NCBI Gene database (https://www.ncbi.nlm.nih.gov/gene). Positive (red) and negative (light blue) significant associations of mRNA expression with high-risk thyroid cancer features, such as earlier age at diagnosis, higher ERK score and lower thyroid differentiation score, etc., are shown. P-values were derived from a two-tailed t-test for linear regression (continuous variables) and a two-sided Wald test for logistic/ordinal regression (binary/ordinal variables). All regression analyses were adjusted for the major somatic oncogenic drivers, including BRAF V600E and N/H/KRAS. Significance threshold was adjusted using Bonferroni correction (p-value ≤ 1e-04). ORIEN - Oncology Research Information Exchange Network; TCGA – The Cancer Genome Atlas; AJCC - American Joint Committee on Cancer.