A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants

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成果类型：

期刊论文

作者：

Han, Yuling;Tan, Lei;Zhou, Ting;Yang, Liuliu;Carrau, Lucia;...

作者机构：

[Zhao, Zeping; Zhu, Jiajun; Tan, Lei; Zhou, Ting; Han, Yuling; Lacko, Lauretta A.; Tan, Christina; tenOever, Benjamin R.; Yang, Liuliu; Evans, Todd; Chen, Shuibing; Giani, Alice Maria; Cahir, Clare; Dong, Xue; Danziger, Ron; Feng, Lingling; Koo, Soyeon; Ba, Qian] Weill Cornell Med Coll, Dept Surg, 1300 York Ave, New York, NY 10065 USA.

[Tan, Lei] Chinese Acad Sci, Inst Biomed & Biotechnol, Shenzhen Inst Adv Technol, Ctr Energy Metab & Reprod, Shenzhen, Peoples R China.

[Zhou, Ting; Zhong, Aaron] Mem Sloan Kettering Canc Ctr, Stem Cell Res Facil, 1275 York Ave, New York, NY 10065 USA.

[Nilsson-Payant, Benjamin E.; Carrau, Lucia] NYU, Dept Microbiol, 430 29th St, New York, NY 10016 USA.

[Rice, Charles M.; Saeed, Mohsan] Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA.

语种：

英文

关键词：

Dengue Virus;NDUFA4;SARS-CoV-2;genome-wide association study;iPSC array;isogenic hiPSC lines;mtDNA;risk allele;single-nucleotide polymorphism;type I interferon

期刊：

Cell Stem Cell

ISSN：

1934-5909

年：

2022

卷：

期：

页码：

1475-1490.e6

DOI：

10.1016/j.stem.2022.09.008

基金类别：

NIDKK [DP3DK111907, R01DK116075, R01DK119667, R01 DK119667-02S1, R01 DK124463, R01DK130454-01, U01 DK127777]; American Diabetes Association [7-20-COVID-211]; Department of Surgery, Weill Cornell Medicine; Bill and Melinda Gates Foundation; Defense Advanced Research Projects Agency [W911NF-16-C-0050]; Marc Haas Foundation; NIAID [R01AI124690, R01AI091707]; Mastercard Diversity-Mentorship Collaborative Research Assistance for Primary Parents Initiative; Eunice Kennedy Shriver NICHD [1F32HD096810-01A 1]; New York State Department of Health (NYSTEM) [C32599, C29156, C32591]; NYSTEM Stem Cell Biology Scholar [DOH01-TRAIN3-2016-00004]

机构署名：

本校为其他机构

院系归属：

化学学院

摘要：

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines...

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A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants

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