Role of Transposable Elements in behavioral traits: insights from six genetic isolates from North-Eastern Italy

Background A significant fraction of mammalian genomes is derived from transposable element (TE) sequences, constituting about half of the human genome, in which retrotransposons such as Alu, LINE-1 and SVA are particularly represented and some of them also have functional roles. Germline transposition of these elements generates polymorphisms between individuals and may be used to study association with phenotypes, inter-individual differences and natural selection. Italy presents an increased number of isolated villages and subpopulations when compared to other European groups, and these isolates provide a desirable study subject to understand the genetic variability of the Italian peninsula. Therefore, we focused on studying the association between polymorphic TEs, behavioral traits (tobacco use and alcohol consumption) and Body Mass Index (BMI) variations, which could lead to an increased risk of developing addiction-related or metabolic diseases, such as tobacco use disorder, alcoholism and obesity. Results We identified 12,709 polymorphic TEs in 589 individuals from six isolates: Principal Component Analysis and Admixture showed that while closely related to other European populations, the isolates tend to cluster amongst themselves and are dominated by drift-induced ancestral components. When performing association tests with GEMMA, several TEs were deemed as significantly associated with a behavioral trait (tobacco use or alcohol consumption) or with BMI variations. Finally, some of the significant TEs also act as expression/alternative splicing quantitative trait loci. Conclusions These results suggest that polymorphic TEs may significantly impact inter-individual and inter-population phenotypic differentiation, while also effectively functioning as variability markers and potentially having a role in susceptibility to medical conditions. In light of these results, isolates could be used as a “laboratory” to investigate this impact and further our understanding about the role of TEs on the human genome.