title: Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9).
abstract: The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restricted by the small number of human A(H7N9) cases. To tackle the stringent significance cutoff of GWAS, we utilized an artificial imputation program SnipSnip to improve the association signals. In single-SNP analysis, one of the top SNPs was rs13057866 of LGALS1. The artificial imputation (AI) identified three non-genotyped causal variants, which can be represented by three anchor/partner SNP pairs rs13057866/rs9622682 (AI P = 1.81 × 10(-7)), rs4820294/rs2899292 (2.13 × 10(-7)) and rs62236673/rs2899292 (4.25 × 10(-7)) respectively. Haplotype analysis of rs4820294 and rs2899292 could simulate the signal of a causal variant. The rs4820294/rs2899292 haplotype GG, in association with protection from A(H7N9) infection (OR = 0.26, P = 5.92 × 10(-7)) correlated to significantly higher levels of LGALS1 mRNA (P = 0.050) and protein expression (P = 0.025) in lymphoblast cell lines. Additionally, rs4820294 was mapped as an eQTL in human primary monocytes and lung tissues. In conclusion, functional variants of LGALS1 causing the expression variations are contributable to the differential susceptibility to influenza A(H7N9).
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Yu
authors: Y
authors: Chen
authors: 1] State Key Laboratory of Emerging Infectious Diseases [2] Department of Microbiology [3] Research Centre of Infection and Immunology.
authors: Jie
authors: J
authors: Zhou
authors: Department of Microbiology.
authors: Zhongshan
authors: Z
authors: Cheng
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Shigui
authors: S
authors: Yang
authors: 1] State Key Laboratory of Emerging Infectious Diseases [2] Department of Microbiology.
authors: Hin
authors: H
authors: Chu
authors: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong.
authors: Yanhui
authors: Y
authors: Fan
authors: Department of Microbiology.
authors: Cun
authors: C
authors: Li
authors: Department of Microbiology.
authors: Bosco Ho-Yin
authors: BH
authors: Wong
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Shufa
authors: S
authors: Zheng
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Yixin
authors: Y
authors: Zhu
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Fei
authors: F
authors: Yu
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Yiyin
authors: Y
authors: Wang
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Xiaoli
authors: X
authors: Liu
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Hainv
authors: H
authors: Gao
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Liang
authors: L
authors: Yu
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Linglin
authors: L
authors: Tang
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Dawei
authors: D
authors: Cui
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, USA.
authors: Ke
authors: K
authors: Hao
authors: Department of Molecular Medicine, Laval University, Canada.
authors: Yohan
authors: Y
authors: Bossé
authors: The University of British Columbia Center for Heart Lung Innovation, St Paul's Hospital, Canada.
authors: Ma'en
authors: M
authors: Obeidat
authors: University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen Research Institute for Asthma and COPD, The Netherlands.
authors: Corry-Anke
authors: CA
authors: Brandsma
authors: Department of Biochemistry, The University of Hong Kong.
authors: You-Qiang
authors: YQ
authors: Song
authors: 1] State Key Laboratory of Emerging Infectious Diseases [2] Department of Microbiology [3] Research Centre of Infection and Immunology [4] Carol Yu Centre for Infection.
authors: Kelvin Kai-Wang
authors: KK
authors: To
authors: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong.
authors: Pak Chung
authors: PC
authors: Sham
authors: 1] State Key Laboratory of Emerging Infectious Diseases [2] Department of Microbiology [3] Research Centre of Infection and Immunology [4] Carol Yu Centre for Infection.
authors: Kwok-Yung
authors: KY
authors: Yuen
authors: 1] State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Lanjuan
authors: L
authors: Li
mesh_terms: D000368:Aged; D002460:Cell Line; D015897:Comorbidity; D000067565:Farmers; D005260:Female; D037483:Galectin 1 / Q000235:genetics*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype; D007251:Influenza, Human / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D037483:Galectin 1