scholarly journals Genome-wide Association Study Identifies New Loci Associated With Risk Of HBV Infection And Disease Progression 

2021 ◽  
Author(s):  
Zheng Zeng ◽  
Liu Hankui ◽  
Xu Huifang ◽  
Lu Haiying ◽  
Yu Yanyan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
East Asian ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Host Genetic ◽  
Host Genetic Factors

Abstract Background: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Results: In order to discover new susceptibility genes for HBV-related outcomes, we conducted a genome-wide association study in 1031 Chinese participants, including 275 HBV clearance subjects, 92 asymptomatic persistence infection carriers (ASPI), 93 chronic hepatitis B patients (CHB), 188 HBV-related decompensated cirrhosis patients (DC), 214 HBV-related hepatocellular carcinoma patients (HCC) and 169 healthy controls (HC). In the case-control study, we observed novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57×10-6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62×10-6; SNP: rs4661093, Gene: ETV3, P = 2.26×10-6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85×10-6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Interestingly, underlying the evolutionary study of HBV-related genes in public database, we found that the derived allele of two HBV clearance related locus, rs3077 and rs9277542, are under strong selection in European population. Conclusions: In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Moreover, we identified two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

scholarly journals Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zheng Zeng ◽  
◽  
Hankui Liu ◽  
Huifang Xu ◽  
Haiying Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Genetic Factors ◽  
East Asian ◽  
Hbv Infection ◽  
Healthy Controls ◽  
Host Genetic ◽  
Host Genetic Factors

Abstract Background Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Methods Collected samples from different outcomes of HBV infection and performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, and Bonferroni method were applied for analysis of genotyping and disease progression. ANOVA was used to evaluate the significance of the association between biomarkers and genotypes in healthy controls. PoMo, FST, Vcftools and Rehh package were used for building the racial tree and population analysis. FST statistics accesses 0.15 was used as a threshold to detect the signature of selection. Results There are 1031 participants passed quality control from 1104 participants, including 275 HBV clearance, 92 asymptomatic persistence infection (ASPI), 93 chronic hepatitis B (CHB), 188 HBV-related decompensated cirrhosis (DC), 214 HBV-related hepatocellular carcinoma (HCC) and 169 healthy controls (HC). In the case–control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57 × 10−6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62 × 10−6; SNP: rs4661093, Gene: ETV3, P = 2.26 × 10−6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85 × 10−6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Underlying the evolutionary study of HBV-related genes in public database, the derived allele of two HBV clearance related loci, rs3077 and rs9277542, are under strong selection in European population. Conclusions In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

scholarly journals Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study

2019 ◽  
Vol 69 (11) ◽  
pp. 1969-1979
Author(s):  
Willem P Brouwer ◽  
Henry L Y Chan ◽  
Pietro Lampertico ◽  
Jinlin Hou ◽  
Pisit Tangkijvanich ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Association Study ◽  
Chronic Hepatitis B ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Pegylated Interferon ◽  
Hbv Dna ◽  
Genome Wide Association ◽  
Genome Wide

AbstractBackground(Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand.MethodsIn this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients.ResultsOf 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= −0.74, standard error [SE] = 0.16, P = 3.44 ×10–6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10–6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele.ConclusionsAlthough no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies.Clinical Trials RegistationNCT01401400.

scholarly journals Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population

2019 ◽  
Vol 30 (5) ◽  
pp. 855-864 ◽  
Author(s):  
Chizu Tanikawa ◽  
Yoichiro Kamatani ◽  
Chikashi Terao ◽  
Masayuki Usami ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Japanese Population ◽  
Quantitative Traits ◽  
Genetic Factors ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Weighted Genetic Risk Score ◽  
Host Genetic ◽  
Host Genetic Factors

BackgroundA family history of urolithiasis is associated with a more than doubling of urolithiasis risk, and a twin study estimating 56% heritability of the condition suggests a pivotal role for host genetic factors. However, previous genome-wide association studies (GWAS) have identified only six risk-related loci.MethodsTo identify novel urolithiasis-related loci in the Japanese population, we performed a large-scale GWAS of 11,130 cases and 187,639 controls, followed by a replication analysis of 2289 cases and 3817 controls. Diagnosis of urolithiasis was confirmed either by a clinician or using medical records or self-report. We also assessed the association of urolithiasis loci with 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (such as body mass index, lipid storage, eGFR, serum uric acid, and serum calcium), using up to 160,000 samples from BioBank Japan.ResultsThe analysis identified 14 significant loci, including nine novel loci. Ten regions showed a significant association with at least one quantitative trait, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic basis for urolithiasis and these quantitative traits. Four novel loci were related to metabolic traits, obesity, hypertriglyceridemia, or hyperuricemia. The remaining ten loci were associated with kidney- or electrolyte-related traits; these may affect crystallization. Weighted genetic risk score analysis indicated that the highest risk group (top 20%) showed an odds ratio of 1.71 (95% confidence interval, 1.42 to 2.06) - 2.13 (95% confidence interval, 2.00 to 2.27) compared with the reference group (bottom 20%).ConclusionsOur findings provide evidence that host genetic factors related to regulation of metabolic and crystallization pathways contribute to the development of urolithiasis.

scholarly journals Genome‐wide association study for host genetic factors associated with equine herpesvirus type‐1 induced myeloencephalopathy

2020 ◽  
Vol 52 (6) ◽  
pp. 794-798
Author(s):  
Wangisa M. B. Dunuwille ◽  
Navid YousefiMashouf ◽  
Udeni B. R. Balasuriya ◽  
Nicola Pusterla ◽  
Ernest Bailey
Keyword(s):  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Equine Herpesvirus ◽  
Herpesvirus Type ◽  
Factors Associated ◽  
Genome Wide ◽  
Equine Herpesvirus Type 1 ◽  
Host Genetic ◽  
Host Genetic Factors
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