TY - JOUR
T1 - Fine–mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians
AU - Guibon, Julie
AU - Sugier, Pierre Emmanuel
AU - Kulkarni, Om
AU - Karimi, Mojgan
AU - Bacq-Daian, Delphine
AU - Besse, Céline
AU - Boland, Anne
AU - Adjadj, Elisabeth
AU - Rachédi, Frédérique
AU - Rubino, Carole
AU - Xhaard, Constance
AU - Mulot, Claire
AU - Laurent-Puig, Pierre
AU - Guizard, Anne Valérie
AU - Schvartz, Claire
AU - Ortiz, Rosa Maria
AU - Ren, Yan
AU - Ostroumova, Evgenia
AU - Deleuze, Jean François
AU - Boutron-Ruault, Marie Christine
AU - Kesminiene, Ausrele
AU - de Vathaire, Florent
AU - Guénel, Pascal
AU - Lesueur, Fabienne
AU - Truong, Thérèse
N1 - Publisher Copyright:
© 2021 Guibon et al.
PY - 2021/3/2
Y1 - 2021/3/2
N2 - Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality. At 2q35, we highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, p = 1.9 x 10-10). It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, p = 7.6 x 10-8) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, p = 0.001). These SNPs are linked to the expression of NRG1 in thyroid tissue. Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.
AB - Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality. At 2q35, we highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, p = 1.9 x 10-10). It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, p = 7.6 x 10-8) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, p = 0.001). These SNPs are linked to the expression of NRG1 in thyroid tissue. Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.
KW - Cancer genetics
KW - Case-control study
KW - Fine-mapping study
KW - Single nucleotide polymorphism
KW - Thyroid cancer
UR - http://www.scopus.com/inward/record.url?scp=85103259187&partnerID=8YFLogxK
U2 - 10.18632/ONCOTARGET.27888
DO - 10.18632/ONCOTARGET.27888
M3 - Article
C2 - 33747362
AN - SCOPUS:85103259187
SN - 1949-2553
VL - 12
SP - 493
EP - 506
JO - Oncotarget
JF - Oncotarget
IS - 5
ER -