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Background: Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations., Methods: We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population., Results: We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10 -7 , 2.39 × 10 -7, and 7.19 × 10 -7 and corresponding odds ratios of 2.02, 1.89, and 2.37., Conclusion: Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated., Competing Interests: The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. None declared. Besides, as the Editorial Board Member of Precision Clinical Medicine, the author Jean-Baptiste Cazier was blinded from reviewing and making decision on this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)