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

ABSTRACTNephrolithiasis is a common urological trait disorder with acute pain. Although previous studies have identified various genetic variations associated with nephrolithiasis, the host genetic factors remain largely unidentified. To identify novel nephrolithiasis loci in the Japanese population, we performed large-scale GWAS (Genome wide association study) using 11,130 cases and 187,639 controls, followed by a replication analysis using 2,289 cases and 3,817 controls. The analysis identified 14 significant loci, including 9 novel loci on 2p23.2-3, 6p21.2, 6p12.3, 6q23.2, 16p12.3, 16q12.2, 17q23.2, 19p13.12, and 20q13.2. Interestingly, 10 of the 14 regions showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic background among nephrolithiasis patients and these quantitative traits. Four novel loci are related to the metabolic pathway, while the remaining 10 loci are associated with the crystallization pathway. Our findings demonstrate the crucial roles of genetic variations in the development of nephrolithiasis.SIGNIFICANCE STATEMENTNephrolithiasis is a common urothelial disorders with frequent recurrence rate, but its genetic background is largely remained unidentified. Previous GWAS identified 6 genetic factors in total. Here we performed a GWAS using more than 200,000 samples in the Japanese populations, and identified 14 significant loci and nine of them are novel. We also found that 10 of the 14 loci showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (BMI, eGFR, UA, Ca etc). All 14 significant loci are associate with either metabolic or crystallization pathways. Thus, our findings elucidated the underlying molecular pathogenesis of nephrolithiasis.

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Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases

Journal of Clinical and Translational Hepatology ◽

10.14218/jcth.2013.010xx ◽

2013 ◽

Vol 1 (1) ◽

Cited By ~ 3

Keyword(s):

Association Study ◽

Liver Diseases ◽

Genetic Factors ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide ◽

Host Genetic ◽

Host Genetic Factors

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

10.21203/rs.3.rs-143403/v1 ◽

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.

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