Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History
2018
Liu, Siyang | Huang, Shujia | Chen, Fang | Zhao, Lijian | Yuan, Yuying | Francis, Stephen Starko | Fang, Lin | Li, Zilong | Lin, Long | Liu, Rong | Zhang, Yong | Xu, Huixin | Li, Shengkang | Zhou, Yuwen | Davies, Robert W. | Liu, Qiang | Walters, Robin G. | Lin, Guang | Ju, Jia | Korneliussen, Thorfinn | Yang, Melinda A. | Fu, Qiaomei | Wang, Jun | Zhou, Lijun | Krogh, Anders | Zhang, Hongyun | Wang, Wei | Chen, Zhengming | Cai, Zhiming | Yin, Ye | Yang, Huanming | Mao, Mao | Shendure, Jay | Wang, Jian | Albrechtsen, Anders | Jin, Xin | Nielsen, Rasmus | Xu, Xun
We analyze whole-genome sequencing data from 141,431 Chinese women generated for non-invasive prenatal testing (NIPT). We use these data to characterize the population genetic structure and to investigate genetic associations with maternal and infectious traits. We show that the present day distribution of alleles is a function of both ancient migration and very recent population movements. We reveal novel phenotype-genotype associations, including several replicated associations with height and BMI, an association between maternal age and EMB, and between twin pregnancy and NRG1. Finally, we identify a unique pattern of circulating viral DNA in plasma with high prevalence of hepatitis B and other clinically relevant maternal infections. A GWAS for viral infections identifies an exceptionally strong association between integrated herpesvirus 6 and MOV10L1, which affects piwi-interacting RNA (piRNA) processing and PIWI protein function. These findings demonstrate the great value and potential of accumulating NIPT data for worldwide medical and genetic analyses.
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