Abstract Previous genetic and public health research in the Pakistani population has focused on the role of consanguinity in increasing recessive disease risk, but little is known about its recent population history or the effects of endogamy. Here, we investigate fine-scale population structure, history and consanguinity patterns using genetic and questionnaire data from &gt;4,000 British Pakistani individuals, mostly with roots in Azad Kashmir and Punjab. We reveal strong recent population structure driven by the biraderi social stratification system. We find that all subgroups have had low effective population sizes (N e ) over the last 50 generations, with some showing a decrease in N e 15-20 generations ago that has resulted in extensive identity-by-descent sharing and increased homozygosity. Using new theory, we show that the footprint of regions of homozygosity in the two largest subgroups is about twice that expected naively based on the self-reported consanguinity rates and the inferred historical N e trajectory. These results demonstrate the impact of the cultural practices of endogamy and consanguinity on population structure and genomic diversity in British Pakistanis, and have important implications for medical genetic studies.

Fine-scale population structure and demographic history of British Pakistanis