L9: Personalised medicine and ethics

What is personalised medicine?

Personalised medicine is an approach to disease prevention and treatment that takes into account individual variability in genes, environment, and lifestyle.

What is another term for personalised medicine?

Precision medicine.

How does personalised medicine work?

Personalised medicine combines pharmacology and genomics to develop effective and safe medications based on an individual's genetic makeup. It also utilizes polygenic risk prediction for prevention and treatment.

What is a polygenic risk score?

A polygenic risk score is the sum of all risk-increasing and risk-decreasing genetic variants weighted by their magnitude of effect.

What are the advantages of personalised medicine?

Personalised medicine can prevent adverse drug effects, determine optimal drug dosages based on genetic makeup, provide more effective and precise therapies, and have the potential for early disease detection and prevention.

What are the ethical issues related to personalised medicine?

Ethical issues include decision-making regarding paediatric genome-wide sequencing, eugenics, carrier screening, ethnicity-specific carrier screening, panethnic carrier screening, and the return of secondary findings in next-generation sequencing.

What is carrier screening?

Carrier screening is a genetic test performed on asymptomatic individuals to determine if they carry genetic variants associated with recessive disorders.

What is the purpose of carrier screening?

Carrier screening is used to screen for disease-causing genetic variants before or during pregnancy, provide information for family planning and reproductive options, and improve prenatal diagnosis and paediatric care management.

What is ethnicity-specific carrier screening?

Ethnicity-specific carrier screening is genetic testing aimed at identifying individuals within specific ethnic groups who carry gene mutations associated with certain inherited conditions.

What are the limitations of ethnicity-specific carrier screening?

Limitations include the potential to miss at-risk couples with multi-ethnic backgrounds and the collective risk posed by rare diseases outweighing that of more common diseases.

Give examples of diseases for which ethnicity-specific carrier screening is commonly performed.

Examples include cystic fibrosis and spinal muscular atrophy (many ethnicities), hemoglobinopathies (Southeast Asian, African, Southern European), familial dysautonomia (Ashkenazi Jewish), and Tay-Sachs disease (Cajun or French Canadian).

What is panethnic carrier screening?

Panethnic carrier screening is genetic screening performed regardless of an individual's ethnic background.

What factors should be considered in panethnic carrier screening?

Factors to consider include clinical severity, medical actionability, technical issues such as sensitivity and specificity, and carrier frequencies.

What are secondary findings in next-generation sequencing?

Secondary findings are findings that are apparently not relevant to the diagnostic indication for which the sequencing was ordered.

What is the difference between research-based and clinical sequencing?

Research-based sequencing involves participants contributing to research and not necessarily expecting any genetic findings, while clinical sequencing is expected to find genetic findings related to the proband's disease.

What are the guidelines for returning secondary findings in clinical sequencing?

Guidelines include the ACMG recommending routine inspection of a panel of 59 genes deemed medically actionable, the ESHG using a filter to avoid unexpected or uninterpretable findings, and the CCMG using a filter to avoid incidental findings but returning highly penetrant incidental findings related to childhood health issues.

What are the main considerations for returning secondary findings?

The main considerations are clinical actionability, gene-disease validity, and variant pathogenicity.

What is eugenics?

Eugenics is a social movement or philosophy that supports enhancing human traits by encouraging the reproduction of desired individuals and traits while discouraging the reproduction of less desired individuals and traits.

What is paediatric genome-wide sequencing?

Paediatric genome-wide sequencing involves sequencing the genome of a child to identify potential genetic risks and disease predispositions.

What are the ethical questions surrounding paediatric genome-wide sequencing?

Ethical questions include whether parents have the right to make decisions regarding sequencing for their child, whether to use whole-genome or limited genetic tests, and whether parents should receive sequencing results regarding the risk of late-onset diseases in their child.

What are incidental findings in genome sequencing?

Incidental findings are findings that are anticipated or unanticipated with genome sequencing and may be unrelated to the original purpose of the testing.

What are the considerations for returning secondary findings in human research?

Participants should have the right to know and decide about the return of results, and if results are returned, they should be provided within a framework of healthcare or counseling.

What is clinical actionability regarding secondary findings?

Clinical actionability means that the findings should have medical relevance and lead to actions that can improve the individual's health.

What is gene-disease validity regarding secondary findings?

Gene-disease validity refers to the established relationship between a specific gene and a particular disease.

What is variant pathogenicity regarding secondary findings?

Variant pathogenicity refers to the clinical significance of a specific genetic variant in causing or increasing the risk of a disease.