Fine–mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians

Julie Guibon, Pierre Emmanuel Sugier, Om Kulkarni, Mojgan Karimi, Delphine Bacq-Daian, Céline Besse, Anne Boland, Elisabeth Adjadj, Frédérique Rachédi, Carole Rubino, Constance Xhaard, Claire Mulot, Pierre Laurent-Puig, Anne Valérie Guizard, Claire Schvartz, Rosa Maria Ortiz, Yan Ren, Evgenia Ostroumova, Jean François Deleuze, Marie Christine Boutron-RuaultAusrele Kesminiene, Florent de Vathaire, Pascal Guénel, Fabienne Lesueur, Thérèse Truong

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    5 Citations (Scopus)

    Résumé

    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.

    langue originaleAnglais
    Pages (de - à)493-506
    Nombre de pages14
    journalOncotarget
    Volume12
    Numéro de publication5
    Les DOIs
    étatPublié - 2 mars 2021

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