Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History

Siyang Liu; Shujia Huang; Fang Chen; Lijian Zhao; Yuying Yuan; Stephen Starko Francis; Lin Fang; Zilong Li; Long Lin; Rong Liu; Yong Zhang; Huixin Xu; Shengkang Li; Yuwen Zhou; Robert W Davies; Qiang Liu; Robin G Walters; Kuang Lin; Jia Ju; Thorfinn Korneliussen; Melinda A Yang; Qiaomei Fu; Jun Wang; Lijun Zhou; Anders Krogh; Hongyun Zhang; Wei Wang; Zhengming Chen; Zhiming Cai; Ye Yin; Huanming Yang; Mao Mao; Jay Shendure; Jian Wang; Anders Albrechtsen; Xin Jin; Rasmus Nielsen; Xun Xu

doi:10.1016/j.cell.2018.08.016

Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History

Cell. 2018 Oct 4;175(2):347-359.e14. doi: 10.1016/j.cell.2018.08.016.

Authors

Siyang Liu¹, Shujia Huang², Fang Chen³, Lijian Zhao⁴, Yuying Yuan⁴, Stephen Starko Francis⁵, Lin Fang⁴, Zilong Li⁶, Long Lin⁶, Rong Liu⁴, Yong Zhang⁴, Huixin Xu⁴, Shengkang Li⁴, Yuwen Zhou⁷, Robert W Davies⁸, Qiang Liu⁴, Robin G Walters⁹, Kuang Lin⁹, Jia Ju⁴, Thorfinn Korneliussen¹⁰, Melinda A Yang¹¹, Qiaomei Fu¹², Jun Wang⁴, Lijun Zhou⁴, Anders Krogh¹³, Hongyun Zhang⁴, Wei Wang⁴, Zhengming Chen⁹, Zhiming Cai¹⁴, Ye Yin⁴, Huanming Yang¹⁵, Mao Mao⁴, Jay Shendure¹⁶, Jian Wang¹⁷, Anders Albrechtsen¹⁸, Xin Jin¹⁹, Rasmus Nielsen²⁰, Xun Xu²¹

Affiliations

¹ BGI-Shenzhen, Shenzhen 518083, Guangdong, China; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
² BGI-Shenzhen, Shenzhen 518083, Guangdong, China; School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China.
³ BGI-Shenzhen, Shenzhen 518083, Guangdong, China; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen 2100, Denmark; BGI-Changyuan, Xinxiang 453400, Henan, China.
⁴ BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
⁵ Division of Epidemiology, University of Nevada, Reno, NV 89557, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143, USA.
⁶ BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, Guangdong, China.
⁷ BGI-Shenzhen, Shenzhen 518083, Guangdong, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, Guangdong, China.
⁸ The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M6H 3W4, Canada.
⁹ Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
¹⁰ Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
¹¹ Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China.
¹² Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China; Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Beijing 100044, China; University of Chinese Academy of Sciences, Beijing 100049, China.
¹³ Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
¹⁴ Department of Urological Surgery, The First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen 518035, Guangdong, China; Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen 518035, Guangdong, China; Shenzhen University Carson International Cancer Center, Shenzhen 518060, Guangdong, China.
¹⁵ BGI-Shenzhen, Shenzhen 518083, Guangdong, China; James D. Watson Institute of Genome Sciences, Hangzhou 310058, Zhejiang, China.
¹⁶ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA.
¹⁷ BGI-Shenzhen, Shenzhen 518083, Guangdong, China; James D. Watson Institute of Genome Sciences, Hangzhou 310058, Zhejiang, China. Electronic address: wangjian@genomics.cn.
¹⁸ Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address: albrecht@binf.ku.dk.
¹⁹ BGI-Shenzhen, Shenzhen 518083, Guangdong, China; School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China. Electronic address: jinxin@genomics.cn.
²⁰ Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen 1350, Denmark; Department of Statistics, University of California, Berkeley, Berkeley, CA 942720, USA. Electronic address: rasmus_nielsen@berkeley.edu.
²¹ BGI-Shenzhen, Shenzhen 518083, Guangdong, China. Electronic address: xuxun@genomics.cn.

PMID: 30290141
DOI: 10.1016/j.cell.2018.08.016

Abstract

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.

Keywords: genome-wide association study; low-pass sequencing; non-invasive prenatal testing; plasma virome; population genetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles
Asian People / genetics*
China
DNA / genetics
Ethnicity / genetics
Female
Gene Frequency / genetics
Genetic Testing
Genetic Variation / genetics
Genetics, Population / methods
Genome-Wide Association Study / methods
Genomics / methods
Human Migration
Humans
Pregnancy
Prenatal Diagnosis / methods*
Sequence Analysis, DNA

Substances

DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding