10 results on '"Greg Gibson"'
Search Results
2. On the utilization of polygenic risk scores for therapeutic targeting.
- Author
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Greg Gibson
- Subjects
Genetics ,QH426-470 - Abstract
The promise of personalized genomic medicine is that knowledge of a person's gene sequences and activity will facilitate more appropriate medical interventions, particularly drug prescriptions, to reduce the burden of disease. Early successes in oncology and pediatrics have affirmed the power of positive diagnosis and are mostly based on detection of one or a few mutations that drive the specific pathology. However, genetically more complex diseases require the development of polygenic risk scores (PRSs) that have variable accuracy. The rarity of events often means that they have necessarily low precision: many called positives are actually not at risk, and only a fraction of cases are prevented by targeted therapy. In some situations, negative prediction may better define the population at low risk. Here, I review five conditions across a broad spectrum of chronic disease (opioid pain medication, hypertension, type 2 diabetes, major depression, and osteoporotic bone fracture), considering in each case how genetic prediction might be used to target drug prescription. This leads to a call for more research designed to evaluate genetic likelihood of response to therapy and a call for evaluation of PRS, not just in terms of sensitivity and specificity but also with respect to potential clinical efficacy.
- Published
- 2019
- Full Text
- View/download PDF
3. PLOS Genetics Data Sharing Policy: In Pursuit of Functional Utility.
- Author
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Gregory S Barsh, Gregory M Cooper, Gregory P Copenhaver, Greg Gibson, Mark I McCarthy, Hua Tang, and Scott M Williams
- Subjects
Genetics ,QH426-470 - Published
- 2015
- Full Text
- View/download PDF
4. Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.
- Author
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Joseph E Powell, Anjali K Henders, Allan F McRae, Jinhee Kim, Gibran Hemani, Nicholas G Martin, Emmanouil T Dermitzakis, Greg Gibson, Grant W Montgomery, and Peter M Visscher
- Subjects
Genetics ,QH426-470 - Abstract
There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.
- Published
- 2013
- Full Text
- View/download PDF
5. Blood-informative transcripts define nine common axes of peripheral blood gene expression.
- Author
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Marcela Preininger, Dalia Arafat, Jinhee Kim, Artika P Nath, Youssef Idaghdour, Kenneth L Brigham, and Greg Gibson
- Subjects
Genetics ,QH426-470 - Abstract
We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB) cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs), generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.
- Published
- 2013
- Full Text
- View/download PDF
6. Guidelines for genome-wide association studies.
- Author
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Gregory S Barsh, Gregory P Copenhaver, Greg Gibson, and Scott M Williams
- Subjects
Genetics ,QH426-470 - Published
- 2012
- Full Text
- View/download PDF
7. Consent and internet-enabled human genomics.
- Author
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Greg Gibson and Gregory P Copenhaver
- Subjects
Genetics ,QH426-470 - Published
- 2010
- Full Text
- View/download PDF
8. A genome-wide gene expression signature of environmental geography in leukocytes of Moroccan Amazighs.
- Author
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Youssef Idaghdour, John D Storey, Sami J Jadallah, and Greg Gibson
- Subjects
Genetics ,QH426-470 - Abstract
The different environments that humans experience are likely to impact physiology and disease susceptibility. In order to estimate the magnitude of the impact of environment on transcript abundance, we examined gene expression in peripheral blood leukocyte samples from 46 desert nomadic, mountain agrarian and coastal urban Moroccan Amazigh individuals. Despite great expression heterogeneity in humans, as much as one third of the leukocyte transcriptome was found to be associated with differences among regions. Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence. Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression. Genetic network analysis further implies that specific aspects of immune function are strongly affected by regional factors and may influence susceptibility to respiratory and inflammatory disease. Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans.
- Published
- 2008
- Full Text
- View/download PDF
9. Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression
- Author
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Kenneth L. Brigham, Jinhee Kim, Greg Gibson, Artika P. Nath, Dalia Arafat, Marcela K. Preininger, and Youssef Idaghdour
- Subjects
Adult ,Cancer Research ,Georgia ,Microarray ,lcsh:QH426-470 ,Population ,Immunology ,Gene Expression ,Context (language use) ,Disease ,Biology ,Body Mass Index ,Transcriptome ,Genetics ,Genetics of the Immune System ,Humans ,Precision Medicine ,education ,Molecular Biology ,Gene ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,B-Lymphocytes ,Microarray analysis techniques ,Systems Biology ,Gene Expression Profiling ,Australia ,Genomics ,Blood Proteins ,Microarray Analysis ,Gene expression profiling ,lcsh:Genetics ,Morocco ,Female ,Genome Expression Analysis ,Research Article - Abstract
We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB) cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as “Blood Informative Transcripts” (BITs), generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli., Author Summary Gene expression profiling of human tissues typically reveals a complex structure of co-regulation of gene expression that has yet to be explored with regard to the genetic and environmental sources of covariance or its implications for quantitative and clinical traits. Here we show that peripheral blood samples from multiple studies can be described by nine common axes of variation that collectively explain up to one half of all transcriptional variance in blood. Specific axes diverge according to environmental variables such as lifestyle and infectious disease exposure, but a strong genetic component to axis regulation is also inferred. As few as 10 “blood-informative transcripts” (BITs) can be used to define each axis and potentially classify individuals with respect to multiple aspects of their blood and immune function. The analysis of longitudinal profiles of one individual shows how these change relative to clinical shifts in metabolic profile following viral infection. The notion that gene expression diverges along genetic paths of least resistance defined by these axes has important implications for interpreting differential expression in case-control studies of disease.
- Published
- 2013
10. A genome-wide gene expression signature of environmental geography in leukocytes of Moroccan Amazighs
- Author
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Youssef Idaghdour, John D. Storey, Sami J. Jadallah, and Greg Gibson
- Subjects
Adult ,Male ,Rural Population ,Cancer Research ,lcsh:QH426-470 ,Adolescent ,Urban Population ,Population ,Population genetics ,Gene Expression ,Biology ,Environment ,Genetics and Genomics/Complex Traits ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Genetic variation ,Genetics ,Ethnicity ,Leukocytes ,Humans ,education ,Molecular Biology ,Life Style ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Genome, Human ,Gene Expression Profiling ,Genetic Variation ,Genetics and Genomics/Gene Expression ,DNA Methylation ,Middle Aged ,Genetic divergence ,Gene expression profiling ,lcsh:Genetics ,Morocco ,030220 oncology & carcinogenesis ,DNA methylation ,Human genome ,CpG Islands ,Female ,Genetics and Genomics/Genetics of the Immune System ,Research Article - Abstract
The different environments that humans experience are likely to impact physiology and disease susceptibility. In order to estimate the magnitude of the impact of environment on transcript abundance, we examined gene expression in peripheral blood leukocyte samples from 46 desert nomadic, mountain agrarian and coastal urban Moroccan Amazigh individuals. Despite great expression heterogeneity in humans, as much as one third of the leukocyte transcriptome was found to be associated with differences among regions. Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence. Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression. Genetic network analysis further implies that specific aspects of immune function are strongly affected by regional factors and may influence susceptibility to respiratory and inflammatory disease. Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans., Author Summary The incidence of complex diseases such as diabetes, asthma, and depression is almost epidemic in many countries and coincides with transition in lifestyles. Clearly this is a result of interaction between modern cultural and environmental factors with the genetic legacy of human history. To estimate the extent of the effects of environmental factors, including lifestyle and geography, on gene expression, we examined gene expression differentiation in peripheral blood leukocyte samples from three Moroccan Amazigh groups leading distinct ways of life: desert nomadic, mountain agrarian and coastal urban. Our data shows that as much as one third of the leukocyte transcriptome is associated with differences among the three regions. Network analysis implies that specific aspects of immune function are strongly affected by regional factors and may influence disease susceptibility. Genetic and methylation differentiation between the three regions is limited and is unlikely to explain the extent of the observed gene expression differentiation. Insight gained from this study highlights the impact transitions from traditional to modern lifestyles likely have on human disease susceptibility and further warrant the need to incorporate gene expression profiling alongside genetic association studies for the prediction of disease susceptibility.
- Published
- 2007
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