Research, including data from 4,000 ORCADES and Viking Health Study – Shetland volunteers, has found 67 regionally enriched genetic variants across the UK that cause disease. While it is known that isolated populations are genetically distinct from their more cosmopolitan counterparts, it is unclear whether larger regions of the British Isles are sufficiently different for this to be relevant to health and disease. Using data from Viking Genes and the large UK Biobank study, researchers from the University of Edinburgh and the Regeneron Genetics Center analysed 18 geographic regions of the British Isles and Ireland, along with 2 Jewish groups.Four populations were clearly distinct from all others in their genetic make-up: the part and full Ashkenazi Jews, Orcadians and Shetlanders. The Northern Isles were about as divergent from the other populations as the part Ashkenazi Jews. Welsh, Irish and mainland Scottish groups were the next most differentiated. The ten regions across England weren’t as genetically distinct, which might reflect the relative lack of geographic or cultural barriers to mixing such as sea channels, mountains or language differences between the English regions studied. Distinctions among regional populations based uponUMAP projections of rare exonic variation The researchers went on to discover 67 disease-causing genetic variants, which were at least five times more common in a particular region. Six of these were enriched in Shetland, including a variant that when two copies are present causes the fatal neurodegenerative condition Batten disease (also called neuronal ceroid lipofuscinosis-1), and a variant which is 138x more common in Shetland than elsewhere, and causes the muscle disorder congenital myotonia when present in both copies of the gene. Further disease variants were found to be enriched in Wales and also Lancashire, Staffordshire and Nottinghamshire in England. In each case, if two carriers were to marry there is a one in four chance of the children having the disorder.The findings highlight the importance of regional gene pools in the UK and call for systematic assessment of the regional frequencies of all rare disease variants. The distinct gene pool of the Jewish population has led to the adoption of targeted genetic screening for monogenic disorders in Jewish populations across the world, including in England. The study demonstrates a similar enrichment of otherwise rare disease-causing variants in regional populations in Britain, particularly in Shetland, but also in Orkney, North and South Wales, Ireland and parts of Mainland Scotland. These findings should feed into strategies for future genetic screening for disease carrier status in these populations. This paper was published in Nature Communications. To read more visit:Regionally enriched rare deleterious exonic variants in the UK and Ireland This article was published on 2024-08-30
