Can medical genetics and evolutionary biology inspire drug target identification?

Wang, Zhongyi; Fu, Liang-Yu; Zhang, Hongyu

doi:10.1016/j.molmed.2011.11.004

Cited by 25 publications

(41 citation statements)

References 10 publications

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“…). Overall, these results show that the enrichment pattern of successful drug targets derived from the new gene‐age data agrees well with the previous results, showing the robustness of the evolutionary patterns of drug targets.…”

Section: Evolutionary Features Of Drug Targetssupporting

confidence: 90%

“…In that study, the human genes were separated into 19 classes with different origins: (1) Prokaryotes, (2) Eukaryota, (3) Opisthokonta, (4) Holozoa, (5) Metazoa, (6) Eumetazoa, (7) Bilateria, (8) Deuterostomia, (9) Chordata, (10) Olfactores, (11) Craniata, (12) Euteleostomi, (13) Tetrapoda, (14) Amniota, (15) Mammalia, (16) Eutheria, (17) Boreoeutheria, (18) Euarchontoglires, and (19) Primates. We revealed that drug target genes did not arise smoothly during macroevolution, but are enriched in genes that originated in classes 1 (Prokaryotes), 5 (Metazoa), and 6 (Eumetazoa) . Moreover, we observed that the drug targets that originated in class 5 (Metazoa) and class 6 (Eumetazoa) are overrepresented by functions for cancer and neurological disease therapy, respectively.…”

Section: Evolutionary Features Of Drug Targetsmentioning

confidence: 88%

“…On the other hand, many human diseases have a genetic component, so genetics can help in differentiating between the causes and consequences of human diseases, which is useful for identifying therapeutic targets . A series of recent studies revealed that successfully targeted genes share certain evolutionary and genetic features . These advances demonstrate that knowledge in modern evolutionary biology and genetics is extremely helpful in identifying potential drug targets, and discovering new drugs as well (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Evolutionary and genetic features of drug targets

Yuan

Wang

Chu

et al. 2018

Medicinal Research Reviews

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In the modern drug discovery pipeline, identification of novel drug targets is a critical step. Despite rapid progress in developing biomedical techniques, it is still a great challenge to find promising new targets from the ample space of human genes. This fact is partially responsible for the situation of "more investments, fewer drugs" in the pharmaceutical industry. A series of recent researches revealed that successfully targeted genes share some common evolutionary and genetic features, which means that the knowledge accumulated in modern evolutionary biology and genetics is very helpful to identify potential drug targets and to find new drugs as well. In this article, we comprehensively summarize the links between human drug targets and genetic diseases and their evolutionary origins, with an attempt to introduce these novel concepts and their medical implications to the biomedical community.

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Section: Evolutionary Features Of Drug Targetssupporting

confidence: 90%

Section: Evolutionary Features Of Drug Targetsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Evolutionary and genetic features of drug targets

Yuan

Wang

Chu

et al. 2018

Medicinal Research Reviews

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“…This end can be achieved most directly through new therapeutics, but also via enhanced diagnostics and biomarkers for the improved targeting of patients and for use in therapeutic development. An increased understanding of the genetic basis of any disease should lead to the development of novel treatment options; of the roughly 500 human genes that have been successfully used as drug targets, ~50 % are also linked to human diseases (Wang et al 2012d). This is substantially higher than the proportion of human genes in the genome that have been linked to disease (roughly 11 %).…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers

Shen

Thompson

Potkin

et al. 2013

Brain Imaging and Behavior

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135

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The Genetics Core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), formally established in 2009, aims to provide resources and facilitate research related to genetic predictors of multidimensional Alzheimer’s disease (AD)-related phenotypes. Here, we provide a systematic review of genetic studies published between 2009 and 2012 where either ADNI APOE genotype or genome-wide association study (GWAS) data were used. We review and synthesize ADNI genetic associations with disease status or quantitative disease endophenotypes including structural and functional neuroimaging, fluid biomarker assays, and cognitive performance. We also discuss the diverse analytical strategies used in these studies, including univariate and multivariate analysis, meta-analysis, pathway analysis, and interaction and network analysis. Finally, we perform pathway and network enrichment analyses of these ADNI genetic associations to highlight key mechanisms that may drive disease onset and trajectory. Major ADNI findings included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU, CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6) that were later replicated on different data sets. Several other genes (e.g., APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI phenotypes, warranting further investigation on other data sets. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future studies employing next-generation sequencing and convergent multi-omics approaches, and for clinical drug and biomarker development.Electronic supplementary materialThe online version of this article (doi:10.1007/s11682-013-9262-z) contains supplementary material, which is available to authorized users.

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“…Notions of the power of genetics to uncover fundamental knowledge drive research agendas and public funding in a variety of fields, from environmental protection (Shostak 2013) to addiction (Midanik 2004). There is great hope by scientists and doctors that genetics will revolutionize medicine through the identification of new pharmaceuticals to treat diseases (Wang, Fu, and Zhang 2012; David et al 2015), genetic screening, and enhanced diagnosis (David et al 2015; Veltman and Lupski 2015). The gene remains potent in the media, with evidence that genetic optimism – the idea that there is a gene for a disorder, that it will be found, and the results will be positive (Conrad 2001a) – continues in media coverage (Ostergren et al 2015; Dingel et al 2014; Bubela and Caulfield 2004).…”

Section: Introductionmentioning

confidence: 99%

“I don’t have to know why it snows, I just have to shovel it!”: Addiction recovery, genetic frameworks, and biological citizenship

et al. 2017

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The gene has infiltrated the way citizens perceive themselves and their health. However, there is scant research that explores the ways genetic conceptions infiltrate individuals’ understanding of their own health as it relates to a behavioral trait, like addiction. Do people seeking treatment for addiction ground their self-perception in biology in a way that shapes their experiences? We interviewed 63 participants in addiction treatment programs, asking how they make meaning of a genetic understanding of addiction in the context of their recovery, and in dealing with the stigma of addiction. About two-thirds of people in our sample did not find a genetic conception of addiction personally useful to them in treatment, instead believing that the cause was irrelevant to their daily struggle to remain abstinent. One-third of respondents believed that an individualized confirmation of a genetic predisposition to addiction would facilitate their dealing with feelings of shame and accept treatment. The vast majority of our sample believed that a genetic understanding of addiction would reduce the stigma associated with addiction, which demonstrates the perceived power of genetic explanations in U.S. society. Our results indicate that respondents (unevenly) ground their self-perception of themselves as an addicted individual in biology.

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Can medical genetics and evolutionary biology inspire drug target identification?

Cited by 25 publications

References 10 publications

Evolutionary and genetic features of drug targets

Evolutionary and genetic features of drug targets

Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers

“I don’t have to know why it snows, I just have to shovel it!”: Addiction recovery, genetic frameworks, and biological citizenship

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