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.

HIV and host immunogenetics: unraveling the role of HLA‐C

“…The study also investigated the role of HLA class I alleles in low VL set‐points. Two HLA alleles – HLA‐B*13:02 and HLA‐C*06:02 was found to be significantly associated with low VL set point and showed a strong linkage disequilibrium between the two alleles ( D ′ = 0.979) . This study has reiterated that it is important to have a global scenario of HLA‐C alleles as well as polymorphisms and their role in HIV disease progression.…”

Host genetic variation and HIV disease: from mapping to mechanism

“…Older studies, referred to as candidate gene studies, were locus or gene-centric, while larger recent studies have searched for correlates across the genome using genome-wide genotyping or whole exome/genome sequencing in an unbiased, “agnostic” manner. In total, five genome-wide association studies (GWAS) of HIV acquisition (Johnson et al 2015 ; Lingappa et al 2011 ; Petrovski et al 2011 ; Joubert et al 2010 ; McLaren et al 2013 ) and 11 of markers of HIV disease course have been reported (Lingappa et al 2011 ; Fellay et al 2009 ; Fellay et al 2007 ; Herbeck et al 2010 ; H. I. V. C. S. International 2010 ; Le Clerc et al 2009 ; Limou et al 2009 ; Pelak et al 2011 ; Pelak et al 2010 ; Troyer et al 2011 ; Wei et al 2015 ). Combining most of these studies, a meta-analysis in individuals of European ancestry of HIV acquisition (McLaren et al 2013 ) and HIV viremia (McLaren et al 2015 ) has also been reported.…”

A post-GWAS analysis of predicted regulatory variants and tuberculosis susceptibility

“…GWAS is based on the premise that causal variants will be in linkage disequilibrium (LD) with the markers present on single nucleotide polymorphism (SNP) arrays. Since 2005, when the first GWAS was published [1], associations have been detected between numerous common genetic variants and several infectious diseases including TB [2–5]. …”