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PMID: 30290141 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Cell ·Vol. 175 ·No. 2 ·2018-00-04 ·Pages 347-359.e14

Liu S, Huang S, Chen F, Zhao L, Yuan Y, Francis SS, Fang L, Li Z, Lin L, Liu R, Zhang Y, Xu H, Li S, Zhou Y, Davies RW, Liu Q, Walters RG, Lin K, Ju J, Korneliussen T, Yang MA, Fu Q, Wang J, Zhou L, Krogh A, Zhang H, Wang W, Chen Z, Cai Z, Yin Y, Yang H, Mao M, Shendure J, Wang J, Albrechtsen A, Jin X, Nielsen R, Xu X

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
MeSH Terms
Adult Alleles Asians/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
Chemicals
DNA
Authors & Affiliations
38 authors, click to expand affiliations / ORCID
Liu Siyang
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
Huang Shujia
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China.
Chen Fang
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.
Zhao Lijian
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Yuan Yuying
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Francis Stephen Starko
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.
Fang Lin
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Li Zilong
BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, Guangdong, China.
Lin Long
BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, Guangdong, China.
Liu Rong
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Zhang Yong
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Xu Huixin
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Li Shengkang
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Zhou Yuwen
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, Guangdong, China.
Davies Robert W
The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M6H 3W4, Canada.
Liu Qiang
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Walters Robin G
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Lin Kuang
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Ju Jia
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Korneliussen Thorfinn
Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
Yang Melinda A
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.
Fu Qiaomei
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.
Wang Jun
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Zhou Lijun
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Krogh Anders
Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.
Zhang Hongyun
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Wang Wei
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Chen Zhengming
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
Cai Zhiming
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.
Yin Ye
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Yang Huanming
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; James D. Watson Institute of Genome Sciences, Hangzhou 310058, Zhejiang, China.
Mao Mao
BGI-Shenzhen, Shenzhen 518083, Guangdong, China.
Shendure Jay
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.
Wang Jian
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; James D. Watson Institute of Genome Sciences, Hangzhou 310058, Zhejiang, China. Electronic address: [email protected].
Albrechtsen Anders
Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address: [email protected].
Jin Xin
BGI-Shenzhen, Shenzhen 518083, Guangdong, China; School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China. Electronic address: [email protected].
Nielsen Rasmus
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: [email protected].
Xu Xun
BGI-Shenzhen, Shenzhen 518083, Guangdong, China. Electronic address: [email protected].
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
Published
2018-00-04
Pages
347-359.e14
Language
English
Region
United States
NLM ID
0413066
Subset
IM
Grants
Medical Research Council · MC_U137686851 · United Kingdom
Wellcome Trust · 212946/Z/18/Z · United Kingdom
Howard Hughes Medical Institute · United States
Medical Research Council · MC_UU_12026/2 · United Kingdom
Medical Research Council · MC_PC_14135 · United Kingdom
Medical Research Council · MC_PC_13049 · United Kingdom
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