Fine-scale population structure and demographic history of British Pakistanis

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• identity-by-descent (IBD) scores

• Our results suggest that, even in the absence of close consanguinity, increased homozygosity due to endogamy is likely to be contributing to recessive disease burden56 and the elevated frequency of rare homozygous knockouts14,57

• We found that rates of consanguinity were under-reported in the mothers and varied significantly between biraderi groups, highlighting differential social practice within the British Pakistani population. Consanguinity rates seemed to be reported somewhat more accurately for the children (Supplementary Fig. 14), possibly because the mothers were more sure of their genetic relationship with their husbands than of that between their parents. We found evidence of multiple generations of recent consanguinity in many families (Supplementary Fig. 14), which contribute to many individuals having higher FROH than expected given the self-reported parental relationships. Our data also suggest that endogamy has contributed to differences in FROH between biraderi groups (Fig. 4d). These results could potentially inform prior expectations about recessive disease risk for British Pakistanis in a clinical genetics setting56. It should be noted that there could be misclassifications with our neural net-based method due to systematic bias in the arbitrary set of modelled consanguineous relationships. Additionally, there is significant variability in the ROH distribution for a given consanguineous relationship, further complicating accurate classification due to overlapping ROH distributions.

• Fifty-seven per cent of the BiB Pakistani mothers reported that their parents were related, and 63% reported being related to their child’s father

• fraction of the genome was homozygous (FROH) in the Pakistani mothers than the White British (mean = 0.048 versus 0.0004, two-sided t test p < 1 × 10−15).