S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Master's Degree_의학과)
Genome-wide association study of thyroid nodules in Koreans suggests overlapping susceptibility loci between thyroid cancer and thyroid nodules
한국인에서 전장 유전체 연관 분석을 통한 갑상선 암과 갑상선 결절의 공통 감수성 유전자좌 연구
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 의학과(중개의학), 2015. 8. 박도준.
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.
Our objective was to identify candidate loci that play a role in thyroid nodules by discovery GWAS.
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.
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.
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.