Guibon Julie, Sugier Pierre-Emmanuel, Kulkarni Om, Karimi Mojgan, Bacq-Daian Delphine, Besse Céline, Boland Anne, Adjadj Elisabeth, Rachédi Frédérique, Rubino Carole, Xhaard Constance, Mulot Claire, Laurent-Puig Pierre, Guizard Anne-Valérie, Schvartz Claire, Ortiz Rosa Maria, Ren Yan, Ostroumova Evgenia, Deleuze Jean-François, Boutron-Ruault Marie-Christine, Kesminiene Ausrele, De Vathaire Florent, Guénel Pascal, Lesueur Fabienne, Truong Thérèse
University Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Exposome and Heredity Team, Villejuif, France.
Inserm, U900, Institut Curie, PSL University, Mines ParisTech, Paris, France.
Oncotarget. 2021 Mar 2;12(5):493-506. doi: 10.18632/oncotarget.27888.
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 . This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, = 1.9 x 10). It is also associated with expression of and of the nearby gene in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, = 7.6 x 10) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, = 0.001). These SNPs are linked to the expression of in thyroid tissue. Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.
分化型甲状腺癌（DTC）的发病率存在广泛的种族和地域差异，大洋洲人群的发病率较高。全基因组关联研究（GWAS）主要在9q22.33、14q13.3、2q35和8p12发现了四个DTC易感位点。在此，我们在包括欧洲人、美拉尼西亚人和波利尼西亚人的EPITHYR联盟人群中对2q35和8p12位点进行了精细定位，以确定DTC风险的可能因果变异。我们使用eQTLs数据进行了共定位分析，以确定因果关系概率最高的单核苷酸多态性（SNP）。在2q35，我们突出了位于……的rs16857609。该SNP在这三个人群中具有较高的因果关系概率，在欧洲人中具有显著关联（优势比[OR]=1.4，P=1.9×10）。它还与甲状腺肿瘤细胞中……和附近基因……的表达相关。在8p12，我们鉴定出rs7844425，其在欧洲人中与DTC显著相关（OR=1.32，P=7.6×10），以及rs2439304，其通过共定位分析被突出，但在我们的数据集中与DTC仅呈中度关联（OR=1.2，P=0.001）。这些SNP与甲状腺组织中……的表达相关。因此，我们的研究确定了2q35和8p12的新变异，应优先进行进一步的功能研究。
