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Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer

Authors
Hwangbo, Y; Lee, EK; Son, HY; Im, SW; Kwak, SJ; Yoon, JW; Kim, MJ; Kim, J; Choi, HS; Ryu, CH; Lee, YJ; Kim, JI; Cho, NH; Park, YJ
Citation
The Journal of clinical endocrinology and metabolism, 103(12):4384-4394, 2018
Journal Title
The Journal of clinical endocrinology and metabolism
ISSN
0021-972X1945-7197
Abstract
CONTEXT: Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown.
OBJECTIVE: To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer.
DESIGN AND SETTING: We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data.
RESULTS: The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26: P = 6.12 x 10-8) and meta-analysis (OR, 1.28: P = 2.11 x 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 x 10-5: rs944289, P = 8.68 x 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues.
CONCLUSIONS: To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.
DOI
10.1210/jc.2017-02439
PMID
30099483
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Preventive Medicine & Public Health
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