Genome-wide association study of thyroid nodules in Koreans suggests overlapping susceptibility loci between thyroid cancer and thyroid nodules

Abstract

Background Genome-wide association studies (GWASs) are widely used in human genetics to identify genes associated with various cancers. Several susceptibility loci of differentiated thyroid cancer (DTC) have been identified by GWASs (FOXE1, NKX2-1, DIRC3, NRG1, IMMP2L, RARRES1, and SNAPC4/CARD9). However, the relationship of these genetic markers with thyroid nodules has not been evaluated. Additionally, susceptibility loci of thyroid nodules have not been identified. Objective Our objective was to identify candidate loci that play a role in thyroid nodules by discovery GWAS. Methods We conducted a one-stage case-control GWAS for thyroid nodules in a population-based cohort. Individuals from the Ansung cohort underwent an initial thyroid ultrasonography and a follow-up 2 years later. Additionally, these individuals were evaluated using 1.43 million genotyped or imputed markers. In the two ultrasonographies, 809 individuals showed solid thyroid nodules in both ultrasonographies, while 689 subjects showed normal thyroids in both. We performed logistic regression adjusting for age and sex.

Results Case-control comparisons identified two independent association signals (P < 1.0 × 10-5): a SNP at 18p11.31 in EPB41L3 (OR = 1.647, P = 2.09 × 10-7) and at 10p11.22 in ITGB1 (OR = 1.645, P = 5.85 × 10-6). In 13 additional suggestive signals (loci with single-point P values between 1.0 × 10-5 and 5.0 × 10-5), SNPs were located near NKX2-1 and RARRES1, which are known thyroid cancer susceptibility loci. Conclusion We found candidate susceptibility loci for thyroid nodules in a one-stage GWAS. Our findings suggest that thyroid nodules and thyroid cancer share a common genetic etiology.