Apolipoprotein E and Protection Against Hepatitis E Viral Infection in American Non-Hispanic Blacks

Hepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/ lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti-HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non- Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%-19.0%) compared with non-Hispanic whites (22.3%, 95% CI 19.1%-25.7%) and Mexican Americans (21.8%, 95% CI 19.0%-25.3%; P \u3c 0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional Ɛ3 and Ɛ4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein thatmediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE Ɛ4 (odds ratio50.5, 95% CI 0.4-0.7; P50.00004) and Ɛ3 (odds ratio50.6, 95% CI 0.4-0.8; P50.001) compared to those carrying APOE Ɛ2. No significant associations were observed between other single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic blacks or between any single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans. Conclusion: Both APOE Ɛ3 and Ɛ4 are significantly associated with protection against HEV infection in non- Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons

Apolipoprotein E and Protection Against Hepatitis E Viral Infection in American Non-Hispanic Blacks

Hepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/ lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti-HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non- Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%-19.0%) compared with non-Hispanic whites (22.3%, 95% CI 19.1%-25.7%) and Mexican Americans (21.8%, 95% CI 19.0%-25.3%; P \u3c 0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional Ɛ3 and Ɛ4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein thatmediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE Ɛ4 (odds ratio50.5, 95% CI 0.4-0.7; P50.00004) and Ɛ3 (odds ratio50.6, 95% CI 0.4-0.8; P50.001) compared to those carrying APOE Ɛ2. No significant associations were observed between other single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic blacks or between any single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans. Conclusion: Both APOE Ɛ3 and Ɛ4 are significantly associated with protection against HEV infection in non- Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons

Consanguinity and susceptibility to infectious diseases in humans.

Studies of animal populations suggest that low genetic heterozygosity is an important risk factor for infection by a diverse range of pathogens, but relatively little research has looked to see whether similar patterns exist in humans. We have used microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increases risk of infection. Our results indicate that inbred individuals are more common among our infected cases for TB and hepatitis, but only in populations where consanguineous marriages are common. No effect was found either for leprosy, which is thought to be oligogenic, or for hepatitis in Italy where consanguineous marriages are rare. Our results suggest that consanguinity is an important risk factor in susceptibility to infectious diseases in humans

Trends in Population-Based Studies of Human Genetics in Infectious Diseases

Pathogen genetics is already a mainstay of public health investigation and control efforts; now advances in technology make it possible to investigate the role of human genetic variation in the epidemiology of infectious diseases. To describe trends in this field, we analyzed articles that were published from 2001 through 2010 and indexed by the HuGE Navigator, a curated online database of PubMed abstracts in human genome epidemiology. We extracted the principal findings from all meta-analyses and genome-wide association studies (GWAS) with an infectious disease-related outcome. Finally, we compared the representation of diseases in HuGE Navigator with their contributions to morbidity worldwide. We identified 3,730 articles on infectious diseases, including 27 meta-analyses and 23 GWAS. The number published each year increased from 148 in 2001 to 543 in 2010 but remained a small fraction (about 7%) of all studies in human genome epidemiology. Most articles were by authors from developed countries, but the percentage by authors from resource-limited countries increased from 9% to 25% during the period studied. The most commonly studied diseases were HIV/AIDS, tuberculosis, hepatitis B infection, hepatitis C infection, sepsis, and malaria. As genomic research methods become more affordable and accessible, population-based research on infectious diseases will be able to examine the role of variation in human as well as pathogen genomes. This approach offers new opportunities for understanding infectious disease susceptibility, severity, treatment, control, and prevention

LUT-NN: Empower Efficient Neural Network Inference with Centroid Learning and Table Lookup

On-device Deep Neural Network (DNN) inference consumes significant computing resources and development efforts. To alleviate that, we propose LUT-NN, the first system to empower inference by table lookup, to reduce inference cost. LUT-NN learns the typical features for each operator, named centroid, and precompute the results for these centroids to save in lookup tables. During inference, the results of the closest centroids with the inputs can be read directly from the table, as the approximated outputs without computations. LUT-NN integrates two major novel techniques: (1) differentiable centroid learning through backpropagation, which adapts three levels of approximation to minimize the accuracy impact by centroids; (2) table lookup inference execution, which comprehensively considers different levels of parallelism, memory access reduction, and dedicated hardware units for optimal performance. LUT-NN is evaluated on multiple real tasks, covering image and speech recognition, and nature language processing. Compared to related work, LUT-NN improves accuracy by 66% to 92%, achieving similar level with the original models. LUT-NN reduces the cost at all dimensions, including FLOPs ($\leq$ 16x), model size ($\leq$ 7x), latency ($\leq$ 6.8x), memory ($\leq$ 6.5x), and power ($\leq$ 41.7%)

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

Abstract Background: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). Conclusions: This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients

Five countries with the largest numbers of infectious disease-related publications in human genome epidemiology (HuGE), 2001–2010.

<p>Five countries with the largest numbers of infectious disease-related publications in human genome epidemiology (HuGE), 2001–2010.</p

Trend in publication of infectious disease-related articles in human genome epidemiology, 2001–2010.

<p>Trend in publication of infectious disease-related articles in human genome epidemiology, 2001–2010.</p

Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection.

The natural outcome and response to treatment in hepatitis C virus (HCV) infection varies between individuals. Whereas some variation may be attributable to viral and environmental variables, it is probable that host genetic background also plays a significant role. Interleukin (IL)-10 has a key function in the regulation of cellular immune responses and in the suppression of pro-inflammatory cytokine secretion. Functional polymorphisms in the IL-10 gene have been described. We investigated the role of these polymorphisms in the outcome of HCV infection, treatment response and development of fibrosis in a case-control association study. Self-limiting infection was associated with the IL-10 (-592) AA genotype (OR=2.05; P=0.028). Persistent infection was associated with the IL-10 (-1082) GG genotype (OR=0.48; P=0.018). Sustained response to interferon therapy was associated with the IL-10 (-1082) GG genotype (OR=2.28; P=0.005) and the haplotype GCC (OR=2.27; P=0.020). The IL-10 (-1082) AA genotype and the ATA/ATA and ACC/ACC homozygous haplotypes were more frequent among patients with rapid fibrosis. Furthermore, the microsatellites IL-10.R and IL-10.G were associated with interferon response with IL-10R.2 conveying susceptibility (OR=1.80; P=0.034), and IL-10R.3 and IL-10.G13 being protective (OR=0.47; P=0.003 and OR=0.59; P=0.042, respectively). We conclude that polymorphisms in the IL-10 promoter appear to have some influence on the outcome of HCV infection, treatment and development of fibrosis