Genetic ancestry and monogenic disease risk in the Scottish Traveller founder population

Abstract

Abstract The Scottish Travellers are a traditionally nomadic community in Scotland that has historically been marginalised, and remained socially isolated from the settled Scottish population until recently. Little, however, is known about their genetic origins, population structure and risks of Mendelian disease. After an approach from the community to address this gap and increase representation, we analyzed array genotypes and whole-exome sequencing data from up to 125 Gypsy/Traveller individuals, alongside settled British and Irish references. We demonstrate that Scottish Travellers are genetically distinct from Irish Travellers, English Gypsies and European Roma, as well as the settled British and Irish populations. However, they do share autosomal and mitochondrial genetic ancestry with settled Scots. Two genetic subgroups are detectable: one which is more drifted and one more admixed. High levels of autozygosity are apparent, consistent with consanguinity. We detect signals of bottlenecks in autosomal and mitochondrial data. Importantly, we identified an enrichment of rare, pathogenic variants, including at least five putative founder variants associated with recessive Mendelian disorders. These findings provide insights into the genetic history of the Scottish Traveller population and highlight the opportunity and need for community-driven clinical genetics screening initiatives to decrease the scope for further health disparities.