title: Genome-Wide Association Studies of HIV-1 Host Control in Ethnically Diverse Chinese Populations.
abstract: Genome-wide association studies (GWASs) have revealed several genetic loci associated with HIV-1 outcome following infection (e.g., HLA-C at 6p21.33) in multi-ethnic populations with genetic heterogeneity and racial/ethnic differences among Caucasians, African-Americans, and Hispanics. To systematically investigate the inherited predisposition to modulate HIV-1 infection in Chinese populations, we performed GWASs in three ethnically diverse HIV-infected patients groups (i.e., HAN, YUN, and XIN, N = 538). The reported loci at 6p21.33 was validated in HAN (e.g., rs9264942, P = 0.0018). An independent association signal (rs2442719, P = 7.85 × 10(-7), HAN group) in the same region was observed. Imputation results suggest that haplotype HLA-B*13:02/C*06:02, which can partially account for the GWAS signal, is associated with lower viral load in Han Chinese. Moreover, several novel loci were identified using GWAS approach including the top association signals at 6q13 (KCNQ5, rs947612, P = 2.15 × 10(-6)), 6p24.1 (PHACTR1, rs202072, P = 3.8 × 10(-6)), and 11q12.3 (SCGB1D4, rs11231017, P = 7.39 × 10(-7)) in HAN, YUN, and XIN groups, respectively. Our findings imply shared or specific mechanisms for host control of HIV-1 in ethnically diverse Chinese populations, which may shed new light on individualized HIV/AIDS therapy in China.
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai 200031, People's Republic of China.
authors.forename: Zejun
authors.initials: Z
authors.lastname: Wei
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai 200031, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
authors.affiliation: CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
authors.affiliation: Infectious Diseases Department, Beijing You'an Hospital, Capital Medical University, Beijing 100069, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Yunnan Provincial Center for Disease Control and Prevention, Kunming 650022, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Henan Provincial Center for Disease Control and Prevention, Zhengzhou 450016, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Yili Prefecture Center for Disease Control and Prevention, Yining 835000, Xinjiang, People's Republic of China.
authors.forename: Zhengjie
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, People's Republic of China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai 200031, People's Republic of China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai 200031, People's Republic of China.
authors.forename: Landian
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, People's Republic of China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
authors.affiliation: Shanghai-MOST Laboratory of Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, People's Republic of China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai 200031, People's Republic of China.
authors.forename: Xiangyin
authors.initials: X
authors.lastname: Kong
mesh_terms: D000328:Adult; D000483:Alleles; D002681:China; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000821:virology*; D015497:HIV-1; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens; D015236:HLA-C Antigens