Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer

Ho-Young Son, Yul Hwangbo, Seong-Keun Yoo, Sun-Wha Im, San Duk Yang, Soo-Jung Kwak, Min Seon Park, Soo Heon Kwak, Sun Wook Cho, Jun Sun Ryu, Jeongseon Kim, Yuh-Seog Jung, Tae Hyun Kim, Su-jin Kim, Kyu Eun Lee, Do Joon Park, Nam Han Cho, Joohon Sung, Jeong-Sun Seo, Eun Kyung Lee (), Young Joo Park () and Jong-Il Kim ()
Additional contact information
Ho-Young Son: Seoul National University College of Medicine
Yul Hwangbo: Seoul National University College of Medicine
Seong-Keun Yoo: Seoul National University Graduate School
Sun-Wha Im: Seoul National University College of Medicine
San Duk Yang: Seoul National University Graduate School
Soo-Jung Kwak: Seoul National University Graduate School
Min Seon Park: Seoul National University College of Medicine
Soo Heon Kwak: Seoul National University College of Medicine
Sun Wook Cho: Seoul National University College of Medicine
Jun Sun Ryu: Center for Thyroid Cancer, National Cancer Center
Jeongseon Kim: Molecular Epidemiology Branch, Research Institute, National Cancer Center
Yuh-Seog Jung: Center for Thyroid Cancer, National Cancer Center
Tae Hyun Kim: Center for Thyroid Cancer, National Cancer Center
Su-jin Kim: Seoul National University College of Medicine
Kyu Eun Lee: Seoul National University College of Medicine
Do Joon Park: Seoul National University College of Medicine
Nam Han Cho: Department of Preventive Medicine Ajou University School of Medicine
Joohon Sung: School of Public Health, Seoul National University
Jeong-Sun Seo: Seoul National University College of Medicine
Eun Kyung Lee: Center for Thyroid Cancer, National Cancer Center
Young Joo Park: Seoul National University College of Medicine
Jong-Il Kim: Seoul National University College of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Thyroid cancer is the most common cancer in Korea. Several susceptibility loci of differentiated thyroid cancer (DTC) were identified by previous genome-wide association studies (GWASs) in Europeans only. Here we conducted a GWAS and a replication study in Koreans using a total of 1,085 DTC cases and 8,884 controls, and validated these results using expression quantitative trait loci (eQTL) analysis and clinical phenotypes. The most robust associations were observed in the NRG1 gene (rs6996585, P=1.08 × 10−10) and this SNP was also associated with NRG1 expression in thyroid tissues. In addition, we confirmed three previously reported loci (FOXE1, NKX2-1 and DIRC3) and identified seven novel susceptibility loci (VAV3, PCNXL2, INSR, MRSB3, FHIT, SEPT11 and SLC24A6) associated with DTC. Furthermore, we identified specific variants of DTC that have different effects according to cancer type or ethnicity. Our findings provide deeper insight into the genetic contribution to thyroid cancer in different populations.

Date: 2017
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DOI: 10.1038/ncomms15966

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