Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Nat Commun. 2021 Dec 10;12(1):7189. doi: 10.1038/s41467-021-27394-2.
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 genotype chip data from 2,200 British Pakistanis. We reveal strong recent population structure driven by the biraderi social stratification system. We find that all subgroups have had low recent effective population sizes (N), with some showing a decrease 15‒20 generations ago that has resulted in extensive identity-by-descent sharing and homozygosity, increasing the risk of recessive disorders. Our results from two orthogonal methods (one using machine learning and the other coalescent-based) suggest that the detailed reporting of parental relatedness for mothers in the cohort under-represents the true levels of consanguinity. These results demonstrate the impact of cultural practices on population structure and genomic diversity in Pakistanis, and have important implications for medical genetic studies.
先前在巴基斯坦人群中的遗传和公共卫生研究集中于近亲婚姻在增加隐性疾病风险方面的作用，但对于其近期人口历史或同婚的影响知之甚少。在这里，我们利用来自 2200 名英国巴基斯坦人的基因芯片数据研究精细的人口结构、历史和近亲婚姻模式。我们揭示了由 biraderi 社会分层系统驱动的强烈的近期人口结构。我们发现所有亚群都有较低的近期有效种群数量 (N)，其中一些在 15-20 代前出现减少，导致广泛的血缘关系和纯合性，增加隐性疾病的风险。我们使用两种正交方法（一种使用机器学习，另一种基于合并）的结果表明，队列中母亲的亲子关系详细报告低估了真正的近亲婚姻水平。这些结果表明，文化习俗对巴基斯坦人口结构和基因组多样性有影响，并对医学遗传研究有重要意义。
