The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

大规模基因研究对所研究人群的医疗保健的好处已有充分记录，但这些基因研究传统上忽略了来自世界某些地区（例如南亚）的人们。在这里，我们描述了从巴基斯坦、印度和孟加拉国的医疗保健服务系统中招募的 4806 名个体的全基因组序列 (WGS) 数据，以及来自孤立的南亚人群的 927 名个体的全基因组序列 (WGS) 数据。我们描述了南亚的人口结构，并描述了针对南亚基因组优化的基因分型阵列 (SARGAM) 和插补参考面板。我们发现证据表明，整个次大陆的生殖隔离、同族通婚和近亲结婚率很高，这些现象各不相同，导致稀有纯合子的水平达到远交种群的 100 倍。创始人效应增强了将功能变异与疾病过程联系起来的能力，并使南亚成为人口规模遗传学研究的独特而强大的地方。