AUTHOR=Natae Shewaye Fituma , Kósa Zsigmond , Sándor János , Merzah Mohammed Abdulridha , Bereczky Zsuzsanna , Pikó Péter , Ádány Róza , Fiatal Szilvia TITLE=The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=Volume 8 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.647416 DOI=10.3389/fcvm.2021.647416 ISSN=2297-055X ABSTRACT=Interactions between genetic and environmental factors contribute to increased risk of VTE. Understanding how these factors interact provides insight for the early identification of at risk groups within a population and creates an opportunity to apply appropriate preventive and curative measures.Thus, we aim to estimate and compare GxE for VTE risk in the general Hungarian and Roma populations. The study was based on data extracted from a database consisting of results previously obtained from a complex health survey. DNA was genotyped for rs121909567(SERPINC1), rs1799963(F2),rs2036914(F11), rs2066865(FGG), rs6025(F5),and rs8176719(ABO) polymorphisms. Multivariable linear regression analysis was applied to test the impact of GxE on VTE risk after interaction terms were created between genetic and VTE risk factors. Interestingly, the rs121909567(SERPINC1) SNP was not present in the general population. However, the risk allele frequency was 1% among the Roma population, which might suggest a founder effect in this minority. This polymorphism interacted with CAD, CKD, cancer, DM, depression, migraine, and obesity. Even though interactions were not statistically significant, the trend of interaction showed the probability of an incremental VTE risk among the Roma population. Five positive and significant GxE interactions were identified in the Roma population. The risk of VTE was higher among depressive Roma subjects who carried the risk variant rs2036914 (β=0.819,p=0.02);however, this interaction was not significant for the general subjects. The joint presence of high levels of LDL-C and rs2066865 increase the VTE risk only among Roma individuals(β=0.389,p=0.002).The possibility of VTE risk increment as a result of a multiplicative interaction between rs8176719 (ABO) and cancer was observed, which was higher for the Roma population (β=0.370, p<0.001) than for the general population (β=-0.042, p=0.6).TheVTE risk increase in the Roma population (β=0.280,p= 0.001) but was higher in the general population (β=0.423,p=0.001) as a result of the multiplicative interaction between CAD and rs2036914.The presence of a multiplicative interaction between rs2066865 and CAD increase VTE risk for the Roma population (β=0.143,p= 0.046).The rs121909567 was confirmed as a founder mutation in the Roma population. As a result of higher genetic load and GxE interactions this minority is at higher risk of VTE compare to the general Hungarian.