Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virus

Kim, Yongchan; Jeong, Byung‐Hoon

doi:10.1007/s00251-020-01188-0

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…Intriguingly, frequencies of the rs34481144-T allele are highly variable across different global ancestries (Auton et al, 2015;Kim and Jeong, 2020), with frequencies as high as 46% in Europe and as low as 0.6% in regions in which flaviviruses are endemic. An intriguing possibility is that evolutionary selection has historically favored the rs34481144-C allele in places with high rates of mosquito-borne RNA virus infections.…”

Section: Discussionmentioning

confidence: 99%

Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells

Wells

Nemesh

Ghosh

et al. 2021

Preprint

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SUMMARYVariation in the human genome contributes to abundant diversity in human traits and vulnerabilities, but the underlying molecular and cellular mechanisms are not yet known, and will need scalable approaches to accelerate their recognition. Here, we advanced and applied an experimental platform that analyzes genetic, molecular, and phenotypic heterogeneity across cells from very many human donors cultured in a single, shared in vitro environment, with algorithms (Dropulation and Census-seq) for assigning phenotypes to individual donors. We used natural genetic variation and synthetic (CRISPR-Cas9) genetic perturbations to analyze the vulnerability of neural progenitor cells to infection with Zika virus. These analyses identified a common variant in the antiviral IFITM3 gene that regulated IFITM3 expression and explained most inter-individual variation in NPCs’ susceptibility to Zika virus infectivity. These and other approaches could provide scalable ways to recognize the impact of genes and genetic variation on cellular phenotypes.HIGHLIGHTSMeasuring cellular phenotypes in iPSCs and hPSC-derived NPCs from many donorsEffects of donor sex, cell source, genetic and other variables on hPSC RNA expressionNatural genetic variation and synthetic perturbation screens both identify IFITM3 in NPC susceptibility to Zika virusA common genetic variant in IFITM3 explains most inter-individual variation in NPC susceptibility to Zika virus

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Section: Discussionmentioning

confidence: 99%

Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells

Wells

Nemesh

Ghosh

et al. 2021

Preprint

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“…However, the prevalence of the rs12252-C allele is heterogeneously distributed among populations. Population-level studies suggested that this allele is rare in European cohorts, but frequent in the Han Chinese cohorts hospitalized with severe H1N1pdm09 infection [ 27 , 33 , 34 , 59 ]. The higher allele frequency of IFITM3 rs12252-C within the Han Chinese population may greatly increase the power of analysis [ 60 ] and partly explain the significant association found within these primary studies [ 29 , 30 , 33 , 35 ], as opposed to studies conducted within European or African-American patient cohorts where the minor allele frequency is much lower and resulted in non-significant associations within these primary studies [ 27 , 28 , 32 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis of host genetic factors associated with influenza severity

et al. 2021

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Background The severity of influenza disease can range from mild symptoms to severe respiratory failure and can partly be explained by host genetic factors that predisposes the host to severe influenza. Here, we aimed to summarize the current state of evidence that host genetic variants play a role in the susceptibility to severe influenza infection by conducting a systematic review and performing a meta-analysis for all markers with at least three or more data entries. Results A total of 34 primary human genetic association studies were identified that investigated a total of 20 different genes. The only significant pooled ORs were retrieved for the rs12252 polymorphism: an overall OR of 1.52 (95% CI [1.06–2.17]) for the rs12252-C allele compared to the rs12252-T allele. A stratified analysis by ethnicity revealed opposite effects in different populations. Conclusion With exception for the rs12252 polymorphism, we could not identify specific genetic polymorphisms to be associated with severe influenza infection in a pooled meta-analysis. This advocates for the use of large, hypothesis-free, genome-wide association studies that account for the polygenic nature and the interactions with other host, pathogen and environmental factors.

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“…The worldwide distribution of the allele frequencies on polymorphisms of the IFITM3, ACE2, TMPRSS2, IL6, and ABO genes was obtained from the 1000 Genomes Project. The polymorphisms analyzed in this study were selected from polymorphisms, which have been reported for an association with SARS-CoV-2, influenza A H1N1 pandemic 2009 virus, and COPD in previous studies [ 6 , 8 , 9 , 10 , 11 , 12 , 13 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Strong Correlation between the Case Fatality Rate of COVID-19 and the rs6598045 Single Nucleotide Polymorphism (SNP) of the Interferon-Induced Transmembrane Protein 3 (IFITM3) Gene at the Population-Level

Kim

Jeong

2020

Genes

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Coronavirus disease 2019 (COVID-19) is a fatal pandemic disease that is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of 13 December, 2020, over 70,000,000 cases and 1,500,000 deaths have been reported over a period of several months; however, the mechanism underlying the pathogenesis of COVID-19 has not been elucidated. To identify the novel risk genetic biomarker for COVID-19, we evaluated the correlation between the case fatality rate of COVID-19 and the genetic polymorphisms of several potential COVID-19-related genes, including interferon-induced transmembrane protein 3 (IFITM3), the angiotensin I converting enzyme 2 (ACE2) gene, transmembrane protease, serine 2 (TMPRSS2), interleukin 6 (IL6), leucine zipper transcription factor-like protein 1 (LZTFL1), and the ABO genes, in various ethnic groups. We obtained the number of COVID-19 cases and deaths from the World Health Organization (WHO) COVID-19 dashboard and calculated the case fatality rate of each ethnic group. In addition, we obtained the allele distribution of the polymorphisms of the IFITM3, ACE2, TMPRSS2, IL6, LZTFL1, and ABO genes from the 1000 Genomes Project and performed Log-linear regression analysis using SAS version 9.4. We found different COVID-19 case fatality rates in each ethnic group. Notably, we identified a strong correlation between the case fatality rate of COVID-19 and the allele frequency of the rs6598045 single nucleotide polymorphism (SNP) of the IFITM3 gene. To the best of our knowledge, this report is the first to describe a strong correlation between the COVID-19 case fatality rate and the rs6598045 SNP of the IFITM3 gene at the population-level.

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Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virus

Cited by 15 publications

References 31 publications

Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells

Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells

A systematic review and meta-analysis of host genetic factors associated with influenza severity

Strong Correlation between the Case Fatality Rate of COVID-19 and the rs6598045 Single Nucleotide Polymorphism (SNP) of the Interferon-Induced Transmembrane Protein 3 (IFITM3) Gene at the Population-Level

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