Microbial genome-wide association studies: lessons from human GWAS

Power, Robert A.; Parkhill, Julian; Oliveira, Túlio de

doi:10.1038/nrg.2016.132

Cited by 239 publications

(243 citation statements)

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“…Thirdly, as previously observed in plants, genomic diversity of pathogenic microbes can be strongly shaped by population stratification (Power et al, 2017). Such population stratification is particularly encountered in haploid and asexual bacteria and/or pathogenic microbes with limited dispersal (Chen and Shapiro, 2015).…”

Section: Why So Few Gwas Of Pathogenicity In Bacteria Fungi and Oomymentioning

confidence: 62%

“…If the last 4 years are documented by a speed in the increasing of studies employing GWAS to detect genes important for pathogenicity in human pathogens (Power et al, 2017), GWA mapping is still poorly used in plant pathology to identify genes related to microbial pathogenicity phenotypes. To our knowledge, the study from Monteil et al (2017) is the only one that attempted to apply GWA mapping to a phytopathogenic bacterium.…”

Section: Why So Few Gwas Of Pathogenicity In Bacteria Fungi and Oomymentioning

confidence: 99%

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Genome-Wide Association Studies In Plant Pathosystems: Toward an Ecological Genomics Approach

2017

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The emergence and re-emergence of plant pathogenic microorganisms are processes that imply perturbations in both host and pathogen ecological niches. Global change is largely assumed to drive the emergence of new etiological agents by altering the equilibrium of the ecological habitats which in turn places hosts more in contact with pathogen reservoirs. In this context, the number of epidemics is expected to increase dramatically in the next coming decades both in wild and crop plants. Under these considerations, the identification of the genetic variants underlying natural variation of resistance is a pre-requisite to estimate the adaptive potential of wild plant populations and to develop new breeding resistant cultivars. On the other hand, the prediction of pathogen's genetic determinants underlying disease emergence can help to identify plant resistance alleles. In the genomic era, whole genome sequencing combined with the development of statistical methods led to the emergence of Genome Wide Association (GWA) mapping, a powerful tool for detecting genomic regions associated with natural variation of disease resistance in both wild and cultivated plants. However, GWA mapping has been less employed for the detection of genetic variants associated with pathogenicity in microbes. Here, we reviewed GWA studies performed either in plants or in pathogenic microorganisms (bacteria, fungi and oomycetes). In addition, we highlighted the benefits and caveats of the emerging joint GWA mapping approach that allows for the simultaneous identification of genes interacting between genomes of both partners. Finally, based on co-evolutionary processes in wild populations, we highlighted a phenotyping-free joint GWA mapping approach as a promising tool for describing the molecular landscape underlying plant - microbe interactions.

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Section: Why So Few Gwas Of Pathogenicity In Bacteria Fungi and Oomymentioning

confidence: 62%

Section: Why So Few Gwas Of Pathogenicity In Bacteria Fungi and Oomymentioning

confidence: 99%

Genome-Wide Association Studies In Plant Pathosystems: Toward an Ecological Genomics Approach

2017

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“…Population structure can be a potential confounding factor in the analysis of NPC‐associated variations . For example, ethnically homogeneous groups are often recruited in human GWAS to minimize the systematic difference amongst samples and hence prevent false positive findings.…”

Section: Resultsmentioning

confidence: 99%

High risk Epstein‐Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma

Hui

Chan

Yang

et al. 2019

Intl Journal of Cancer

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Whether certain variants of Epstein–Barr virus (EBV) are linked to the pathogenesis of nasopharyngeal carcinoma (NPC), which shows a marked geographic restriction, remains an unresolved issue. We performed a case–control study comparing genomic sequences of EBV isolated from saliva samples of 142 population carriers with those from primary tumour biopsies derived from 62 patients with NPC of Hong Kong. Cluster analysis discovered five EBV subgroups 1A‐C and 2A‐B amongst the population carriers in contrast to the predominance of 1A and ‐B in the majority of NPC. Genome‐wide association study (GWAS) identified a panel of NPC‐associated single nucleotide polymorphisms (SNPs) and indels in the EBER locus. The most significant polymorphism, which can be found in 96.8% NPC cases and 40.1% population carriers of Hong Kong, is a four‐base‐deletion polymorphism downstream of EBER2 (EBER‐del) from coordinates 7188–7191 (p = 1.91 × 10−7). In addition, the predicted secondary structure of EBER2 is altered with likely functional consequence in nearly all NPC cases. Using the SNPs and indels associated with NPC, genetic risk score is assigned for each EBV variant. EBV variants with high genetic risk score are found to be much more prevalent in Hong Kong Chinese than individuals of other geographic regions and in NPC than other EBV‐associated cancers. We conclude that high risk EBV variants with polymorphisms in the EBER locus, designated as HKNPC‐EBERvar, are strongly associated with NPC. Further investigation of the biological function and potential clinical application of these newly identified polymorphisms in NPC and other EBV‐associated cancers is warranted.

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“…Another future opportunity in gut microbiota research is microbial metagenomic GWAS, which, so far, has only been used in the study of pathogenic microorganisms [51]. Although a number of analytical advances are required to handle the unique features of microbial genomics, such an approach could provide exciting new insights into the effects of microbial variants and, if integrated with human genomic data, how they may be dependent on the human genetic background.…”

Section: Towards Novel Prevention and Treatment Strategies For Type 2mentioning

confidence: 99%

The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities

2017

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The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. During the last decade, evidence has accumulated to support a role for gut microbiota (analysed from faecal samples) in glycaemic control and type 2 diabetes. Mechanistic studies in mice support a causal role for gut microbiota in metabolic diseases, although human data favouring causality is insufficient. As it may be challenging to sort the human evidence from the large number of animal studies in the field, there is a need to provide a review of human studies. Thus, the aim of this review is to cover the current and future possibilities and challenges of using the gut microbiota, with its capacity to be modified, in the development of preventive and treatment strategies for hyperglycaemia and type 2 diabetes in humans. We discuss what is known about the composition and functionality of human gut microbiota in type 2 diabetes and summarise recent evidence of current treatment strategies that involve, or are based on, modification of gut microbiota (diet, probiotics, metformin and bariatric surgery). We go on to review some potential future gut-based glucose-lowering approaches involving microbiota, including the development of personalised nutrition and probiotic approaches, identification of therapeutic components of probiotics, targeted delivery of propionate in the proximal colon, targeted delivery of metformin in the lower gut, faecal microbiota transplantation, and the incorporation of genetically modified bacteria that express therapeutic factors into microbiota. Finally, future avenues and challenges for understanding the interplay between human nutrition, genetics and microbial genetics, and the need for integration of human multi-omic data (such as genetics, transcriptomics, epigenetics, proteomics and metabolomics) with microbiome data (such as strain-level variation, transcriptomics, proteomics and metabolomics) to make personalised treatments a successful future reality are discussed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-017-4278-3) contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, which is available to authorised users.

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Microbial genome-wide association studies: lessons from human GWAS

Cited by 239 publications

References 64 publications

Genome-Wide Association Studies In Plant Pathosystems: Toward an Ecological Genomics Approach

Genome-Wide Association Studies In Plant Pathosystems: Toward an Ecological Genomics Approach

High risk Epstein‐Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma

The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities

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