scholarly journals Molecular genetic studies of complex phenotypes

2012 ◽  
Vol 159 (2) ◽  
pp. 64-79 ◽  
Author(s):  
Ali J. Marian
Author(s):  
Michael Windle

This chapter provides an introduction and overview of important issues that served as motivations for this book. For many complex phenotypes (e.g., depression, diabetes, obesity, substance use), there is substantial evidence that while genetic influences are important, so are environmental influences; moreover, there is substantial evidence from both behavior genetic studies (e.g., twin and adoptee studies) and molecular genetic studies (both human and infrahuman) that genes commonly interact with environmental factors in predicting complex phenotypes. The fields of genomics and other –omics (e.g., proteomics, metabolomics) provide exciting opportunities to advance science and foster the goals of public health and a more individualized intervention approach (e.g., precision medicine). The goals of these more individualized approaches would benefit greatly not only by advances in genomics and other –omics, but also by incorporating information both on environments and their interactions with genomic and other biological material and regulatory processes (e.g., environmental signal to biological pathway responses). Such findings would thereby offer more flexible guidance to a broader range of prevention, intervention, and treatment targets, and facilitate more tailored programs based on a fuller complement of G and E influences.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2431
Author(s):  
Natalia A. Shnayder ◽  
Marina M. Petrova ◽  
Tatiana E. Popova ◽  
Tatiana K. Davidova ◽  
Olga P. Bobrova ◽  
...  

Chronic pain syndromes are an important medical problem generated by various molecular, genetic, and pathophysiologic mechanisms. Back pain, neuropathic pain, and posttraumatic pain are the most important pathological processes associated with chronic pain in adults. Standard approaches to the treatment of them do not solve the problem of pain chronicity. This is the reason for the search for new personalized strategies for the prevention and treatment of chronic pain. The nitric oxide (NO) system can play one of the key roles in the development of peripheral pain and its chronicity. The purpose of the study is to review publications devoted to changes in the NO system in patients with peripheral chronical pain syndromes. We have carried out a search for the articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar databases. The search was carried out using keywords and their combinations. The role of NO and NO synthases (NOS) isoforms in peripheral pain development and chronicity was demonstrated primarily from animal models to humans. The most studied is the neuronal NOS (nNOS). The role of inducible NOS (iNOS) and endothelial NOS (eNOS) is still under investigation. Associative genetic studies have shown that single nucleotide variants (SNVs) of NOS1, NOS2, and NOS3 genes encoding nNOS, iNOS, and eNOS may be associated with acute and chronic peripheral pain. Prospects for the use of NOS inhibitors to modulate the effect of drugs used to treat peripheral pain syndrome are discussed. Associative genetic studies of SNVs NOS1, NOS2, and NOS3 genes are important for understanding genetic predictors of peripheral pain chronicity and development of new personalized pharmacotherapy strategies.


Author(s):  
David Lewis-Smith ◽  
Shiva Ganesan ◽  
Peter D. Galer ◽  
Katherine L. Helbig ◽  
Sarah E. McKeown ◽  
...  

AbstractWhile genetic studies of epilepsies can be performed in thousands of individuals, phenotyping remains a manual, non-scalable task. A particular challenge is capturing the evolution of complex phenotypes with age. Here, we present a novel approach, applying phenotypic similarity analysis to a total of 3251 patient-years of longitudinal electronic medical record data from a previously reported cohort of 658 individuals with genetic epilepsies. After mapping clinical data to the Human Phenotype Ontology, we determined the phenotypic similarity of individuals sharing each genetic etiology within each 3-month age interval from birth up to a maximum age of 25 years. 140 of 600 (23%) of all 27 genes and 3-month age intervals with sufficient data for calculation of phenotypic similarity were significantly higher than expect by chance. 11 of 27 genetic etiologies had significant overall phenotypic similarity trajectories. These do not simply reflect strong statistical associations with single phenotypic features but appear to emerge from complex clinical constellations of features that may not be strongly associated individually. As an attempt to reconstruct the cognitive framework of syndrome recognition in clinical practice, longitudinal phenotypic similarity analysis extends the traditional phenotyping approach by utilizing data from electronic medical records at a scale that is far beyond the capabilities of manual phenotyping. Delineation of how the phenotypic homogeneity of genetic epilepsies varies with age could improve the phenotypic classification of these disorders, the accuracy of prognostic counseling, and by providing historical control data, the design and interpretation of precision clinical trials in rare diseases.


1996 ◽  
Vol 17 (4) ◽  
pp. S25-S26
Author(s):  
H. Furukawa ◽  
H. Tashiro ◽  
Y. Tanaka ◽  
C. Yutani ◽  
T. Yamaguchi ◽  
...  

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