Institute for Human Genetics, University of California, San Francisco, CA, 94143, USA.
Dept of Ornithology and Mammology, California Academy of Sciences, San Francisco, CA, 94118, USA.
Nat Commun. 2023 Jun 8;14(1):3377. doi: 10.1038/s41467-023-38766-1.
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.
大规模遗传研究对所研究人群的医疗保健的好处已有充分记录，但这些遗传研究传统上忽略了来自世界某些地区的人群，如南亚。在这里，我们描述了来自巴基斯坦、印度和孟加拉国医疗保健系统的 4806 个人的全基因组序列 (WGS) 数据，以及来自 927 名孤立的南亚人群的 WGS。我们描述了南亚的人口结构，并描述了一个针对南亚基因组优化的基因分型阵列 (SARGAM) 和 imputation 参考面板。我们发现了生殖隔离、近亲繁殖和血缘关系的高比率的证据，这些比率在次大陆各地有所不同，导致罕见纯合子的水平达到了与外婚人群相比的 100 倍。奠基者效应增加了将功能变体与疾病过程相关联的能力，使南亚成为进行人口规模遗传研究的独特有力之地。
