**Abstract**

Differentiated thyroid carcinoma (DTC) represents more than 90% of all thyroid cancer histological types. Its incidence has increased at a faster rate than most other malignancies during the last three decades and varies considerably around the world. The familial form of the disease has also become more common than previously reported, accounting for 5−15% of DTC cases. The main established risk factor of thyroid cancer is exposure to ionizing radiation, particularly if occurred during childhood. Thyroid cancer (including DTC) is also characterized by having one of the highest familial risks of any cancer supporting heritable predisposition. In spite of such a high familial risk, linkage analysis in non-syndromic DTC families (i.e. families where DTC is the primary cancer) performed two decades ago mapped several susceptibility loci but did not lead to the identification of high-penetrance causal germline variants. More recently, genome-wide association studies based on population case–control studies identified a limited number of DTC-associated loci and suggested that multiple low penetrance genes are involved in predisposition to DTC. This chapter reviews known genetic factors predisposing to DTC as well as approaches used to map them in various populations, and opens up on alternative strategies that could help to understand DTC tumorigenesis.

**Keywords:** differentiated thyroid cancer, familial risk, case–control study, genetic predisposition, genome-wide association study
