Ancient implications for today’s precision medicine: How the first Near East farmers shaped the European genetic risk architecture for IBD

Abstract Inflammatory bowel disease (IBD) is often described as a model for modern civilization diseases in which environmental factors trigger disease manifestation in genetically compromised individuals. Little is known about the evolutionary history of variants associated with IBD in modern Europeans. Here, we analysed 610 IBD-variants in 2445 ancient datasets from human remains spanning the last 12,000 years, including genotypes generated from 172 newly collected individuals from the European Neolithic. We found statistically significant differences in the frequencies of 97 IBD variants between Neolithic and modern populations that can be explained by the adoption of an agricultural lifestyle and behaviour and concomitant possible microbiome changes in the earliest farmers. Later admixture events and selection against pathogens largely influenced the genetic risk architecture of IBD in contemporary Europeans. A better understanding of the evolutionary history of disease variants is an important first step in translating genetic findings into preventive health care.