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Printable Handouts
Navigable Slide Index
- Introduction
- Table of contents: Background
- Influence of genetics on response to treatments
- Types of studies
- Evidence for the role of genetics in treatment outcomes
- How many genes/variants are involved?
- Table of contents: Current clinical applications
- Relevance of pharmacogenetics (PGx) in psychiatry
- Candidate genes
- CYP2C19/CYP2D6 and drug metabolism
- CYP450 functional groups
- PGx in clinical guidelines
- PGx biomarkers in drug labels (FDA)
- CYP2C19/CYP2D6 polymorphisms in practice: examples
- Some scientific evidence
- CYP2C19 in (es)citalopram side effects
- CYP2C19 in (es)citalopram efficacy
- Practicalities: when & to whom should we recommend PGx testing?
- Is pharmacogenetic testing ready for a store near you?
- FDA safety communication
- PGx for drug repositioning & development of new drugs
- Table of contents: Limitations
- Is PGx testing according to guidelines part of routine clinical practice?
- PGx cost-effectiveness in psychiatry
- Other issues of PGx
- People of European descent account for 88% of genomes in GWAS
- Prevalence of CYP2D6/CYP2C19 PM & UM across ethnic groups
- Role of genes involved in drug pharmacodynamics?
- The problem of power (1)
- Previous GWASs
- The problem of power (2)
- Polygenic risk scores (PRS): a possible prediction approach
- PRS of schizophrenia and treatment response
- Table of contents: The future
- Consortia: a powerful strategy to increase the power of PGx studies
- Biobanks
- Whole genome sequencing
- Conclusion: PGx in the future
- Useful websites
Topics Covered
- Pharmacogenetics
- Impact of genetics on drug response
- Pharmacogenetics in psychiatry
- Pharmacogenetic clinical guidelines
- Pharmacogenetic testing
- Drug development
- Pharmacodynamics
Links
Series:
Categories:
Therapeutic Areas:
External Links
- Genes and drug metabolism
- Clinical Pharmacogenetics Implementation Consortium (CPIP)
- Dutch Pharmacogenetic Working Group (DPWG)
- PGx biomarkers in drug labels (FDA)
- Ubiquitous Pharmacogenomics (European study)
- Antidepressant response group of the Psychiatric Genomics Consortium (PGC)
- The International Consortium on Lithium Genetics (ConLiGen)
- Clozapine-induced Agranulocytosis Consortium (CIAC) of the Psychiatric Genomics Consortium (PGC)
- deCODE genetics
- UK Biobank
- Danish National Biobank
- All of Us
- PharmGKB
- International Sociaty of Psychiatric Genetics (ISPG) Genetic Testing Statement
Talk Citation
Fabbri, C. (2021, April 27). Genetics and psychotropic drugs: present and future clinical applications [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 14, 2024, from https://doi.org/10.69645/GZLU3270.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
A selection of talks on Genetics & Epigenetics
Transcript
Please wait while the transcript is being prepared...
0:00
Hello. My name is Chiara Fabbri.
I'm a psychiatrist, and I work as
a Marie Curie Research Fellow at the Institute of Psychiatry,
Psychology and Neuroscience, King's College London.
During this presentation, part of the Henry Stewart Talks series on pharmacogenetics,
I will walk you through the main concepts of psychiatric pharmacogenetics,
which is the study of how genetic variants influence
the way we respond or have side effects to psychiatric medications.
0:31
This is the table of contents of topics that I will discuss.
I want to start with a very simple question.
Why is genetics relevant to psychopharmacotherapy?
0:43
Each pair of individuals is estimated to differ
in about five million variants in their genomes.
This includes single nucleotide polymorphisms or SNPs,
that are substitutions of a single DNA base pair,
and copy number variations,
which consists of the insertions and deletions.
These differences are responsible for
inter-individual variability in the way the proteins in our cells are built and function,
either directly or through the changes in the activity of regulatory elements.
As a result, there are differences in the way
different individuals respond to internal stimuli,
such as hormones or neurotransmitters,
and to external stimuli such as drugs.
1:28
There are three main methodological approaches to
the study of how genetic variants influence the response to drugs.
The first one to be developed was a candidate gene approach,
that apply selective genotyping of variants in genes
which are involved in drug metabolism or pharmacokinetics,
or drug mechanism of action, or pharmacodynamics.
This method is limited by our previous knowledge.
Thus, in the last 10 years,
Genome-Wide Association Studies, or GWAS,
became the most common approach.
In GWAS, hundred of thousands or millions
of common variants have been genotyped across the genome
thanks to a cost-effective technology called a microarray.
The genotyped variants are spread across the genome
and they cover the known common genetic variation in humans,
in order to include all these variants in GWAS,
without a priori hypothesis.
Common variants are usually defined as those having
a frequency of at least one percent in the population.
In the last few years,
next-generation sequencing has become more feasible in terms of cost,
and it provides the possibility to explore
the role of rare and unknown variance in coding regions,
namely axons, or the complete genomic sequence.
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