Many types of variants in the MEFV gene are associated with FMF. The five most commonly identified mutation types have been denoted as the founder mutations^7,8. An association between ethnicity and the type of variant has been suggested, but a clear connection has not been established¹⁷. This study was conducted in order to demonstrate such link: We sought to demonstrate that a patient’s variant could be predicted based on his/her family origins. Given the ancestral diversity of the large study population and the fact that the subjects rarely had a single country of origin, we constructed a model using machine learning in order to perform statistical analysis. We introduced an origin score to quantify the ethnic complexity of each individual.

Analysis of the study population, which included 1781 Israeli referrals for FMF testing mainly due to FMF suspicion, allowed us to extract reliable results despite the ethnic diversity of the study population. Our results showed that the p.Met694Val variant was the most prevalent among the study population, identified in 72% of studied subjects. Referrals whose parents or grandparents came to Israel from Tunisia, Libya, Algeria, or Morocco were most likely to carry this specific variant. The second most common mutation, p.Glu148Gln, was observed in 23% of the cohort; the most common countries of origin were Iran, Yemen, India, and Ukraine. The p.Val726Ala variant was the third most common, found in 19% of subjects. The countries of…