Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B

Jiang, De Ke; Peng, Xiao; Yu, Hongjie; Cao, Guangwen; Ding, Dong; Chen, Haitao; Huang, Haoran; Gao, Yu Zhen; Wu, Xiaoxian; Long, Xi; Zhang, Hongxing; Zhang, Youjie; Gao, Yong; Chen, Tao Yang; Ren, Wei; Zhang, Pengyin; Shi, Zhuqing; Jiang, Wei; Wan, Bo; Saiyin, Hexige; Yin, Jianhua; Zhou, Yuan; Zhai, Yun; Lu, Pei Xin; Zhang, Hongwei; Gu, Xiaoli; Tan, Aihua; Wang, Jin Bing; Zuo, Xian Bo; Sun, Liang; Liu, Jun O.; Yi, Qing; Mo, Zengnan; Zhou, Gangqiao; Liu, Ying; Sun, Jielin; Shugart, Yin Yao; Zheng, S. Lilly; Zhang, Xue Jun; Xu, Jianfeng; Liu, Yu

doi:10.1002/hep.27794

Cited by 79 publications

(94 citation statements)

References 43 publications

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“…To the best of our knowledge only a few of the findings were previously known; however reassuringly these replicated as expected: IL18/rs75649625 and rs4129267/IL6R [20], as well as AGER/sRAGE, CD40 and LGALS3 cis associations [17,21,22] and the rs8176741/TEK trans association [23], and the rs635634/SELE [24]. In contrast, six of the 79 pQTLs did not replicate.…”

Section: Discussionmentioning

confidence: 51%

Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease

Folkersen¹,

et al. 2017

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Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.

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Section: Discussionmentioning

confidence: 51%

Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease

Folkersen¹,

et al. 2017

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“…Common genetic signatures between autoimmune and infectious diseases indirectly imply that pathogens can indeed trigger autoimmunity. In line with this second hypothesis, we have identified common risk factors between autoimmune and infectious diseases, such as the alleles: HLA-DRB1*15 for MS, SLE (Table 1), and leprosy (OR = 2.11; P = 3.5 × 10 –28 ) [87]; rs9275572*C, located in HLA-DQ, for chronic HCV infection (OR = 0.71; P = 2.62 × 10 –6 ) [84], and SLE ( P = 1.94 × 10 –6 ) [119]; HLA-DQB1*03:02 for MS (OR = 1.30; P = 1.8 × 10 –22 ) [45] and pulmonary tuberculosis (OR = 0.59; P = 2.48 × 10 –5 ) [67]; HLA-C*12:02 for UC (OR = 2.25; P = 4 × 10 –37 ) [46], CD (OR = 1.44; P = 3x 10 –8 ) [46], and chronic HBV infection (OR = 1.70; P = 7.79 × 10 –12 ) [63]; and rs378352*T, located in HLA-DOA, for chronic HBV infection (OR = 1.32; P = 1.16 × 10 –7 ) [78] and RA (OR = 1.24; P = 4.6 × 10 –6 ) [25] (Fig. 2a).…”

Section: Relationship Between the Mhc Variants Involved In Autoimmunementioning

confidence: 99%

The MHC locus and genetic susceptibility to autoimmune and infectious diseases

et al. 2017

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In the past 50 years, variants in the major histocompatibility complex (MHC) locus, also known as the human leukocyte antigen (HLA), have been reported as major risk factors for complex diseases. Recent advances, including large genetic screens, imputation, and analyses of non-additive and epistatic effects, have contributed to a better understanding of the shared and specific roles of MHC variants in different diseases. We review these advances and discuss the relationships between MHC variants involved in autoimmune and infectious diseases. Further work in this area will help to distinguish between alternative hypotheses for the role of pathogens in autoimmune disease development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1207-1) contains supplementary material, which is available to authorized users.

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“…Among two HBV-and immune-related SNPs in the CFB and CD40 regions (14,15) and three hepatitis C virus-related SNPs in the IFNL4 regions, (16)(17)(18) allele type differences can be found between Africa and Europe or between Africa and South Asia ( Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

“…Based on a literature review, 12 HBV-and HLArelated SNPs, (7)(8)(9)(10)(11)(12)(13) five hepatitis-and immune-related SNPs in complement factor B (CFB), clusters of differentiation molecule 40 (CD40), and interferon lambda 4 (IFNL4) loci (14)(15)(16)(17)(18) , and five nasopharyngeal carcinoma (NPC)-related SNPs in HLA regions (19)(20)(21) were selected for this analysis (Tables 1 and 2). These SNP data from around the world were downloaded from the phase 3 data of 1,000 genomes (http://www.…”

Section: Methodsmentioning

confidence: 99%

A global perspective on hepatitis B‐related single nucleotide polymorphisms and evolution during human migration

Tai

Jeng

Lin

2017

Hepatology Communications

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Genome‐wide association studies have indicated that human leukocyte antigen (HLA)‐DP and HLA‐DQ play roles in persistent hepatitis B virus (HBV) infection in Asia. To understand the evolution of HBV‐related single nucleotide polymorphisms (SNPs) and to correlate these SNPs with chronic HBV infection among different populations, we conducted a global perspective study on hepatitis‐related SNPs. We selected 12 HBV‐related SNPs on the HLA locus and two HBV and three hepatitis C virus immune‐related SNPs for analysis. Five nasopharyngeal carcinoma‐related SNPs served as controls. All SNP data worldwide from 26 populations were downloaded from 1,000 genomes. We found a dramatic difference in the allele frequency in most of the HBV‐ and HLA‐related SNPs in East Asia compared to the other continents. A sharp change in allele frequency in 8 of 12 SNPs was found between Bengali populations in Bangladesh and Chinese Dai populations in Xishuangbanna, China (P < 0.001); these areas represent the junction of South and East Asia. For the immune‐related SNPs, significant changes were found after leaving Africa. Most of these genes shifted from higher expression genotypes in Africa to lower expression genotypes in either Europe or South Asia (P < 0.001). During this two‐stage adaptation, immunity adjusted toward a weak immune response, which could have been a survival strategy during human migration to East Asia. The prevalence of chronic HBV infection in Africa is as high as in Asia; however, the HBV‐related SNP genotypes are not present in Africa, and so the genetic mechanism of chronic HBV infection in Africa needs further exploration. Conclusion: Two stages of genetic changes toward a weak immune response occurred when humans migrated out of Africa. These changes could be a survival strategy for avoiding cytokine storms and surviving in new environments. (Hepatology Communications 2017;1:1005–1013)

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Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B

Cited by 79 publications

References 43 publications

Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease

Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease

The MHC locus and genetic susceptibility to autoimmune and infectious diseases

A global perspective on hepatitis B‐related single nucleotide polymorphisms and evolution during human migration

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