$$PRS = \sum_{i=1}^{n} G_i \times \beta_i$$

Question 1

Which of the following best describes a Polygenic Risk Score (PRS)?

Accepted Answer

A summary measure of genome-wide genotype data, weighted by effect sizes from GWAS, indicating genetic liability to a trait or disorder.

Question 2

How is a PRS typically calculated?

Accepted Answer

By summing the number of risk alleles, each weighted by their effect size from GWAS summary statistics.

Question 3

In the context of breast cancer screening, what did the use of PRS demonstrate?

Accepted Answer

Women in the top 5% of PRS reach the average 10-year risk threshold for screening a decade earlier than the general population.

Question 4

Which of the following is a limitation of using PRS in clinical care?

Accepted Answer

The predictive ability of PRS is currently limited in non-European populations due to differences in allele frequencies and linkage disequilibrium.

Question 5

What is one potential clinical application of PRS in neuropsychiatric disorders?

Accepted Answer

Predicting which individuals with high-risk CNVs are more likely to develop schizophrenia.

Question 6

Why might combining PRS for multiple traits improve prediction accuracy?

Accepted Answer

Because traits often have genetic correlations, and combining PRSs can capture additional genetic information.

Question 7

Which equation best represents the calculation of a PRS?

Accepted Answer

$$PRS = \sum_{i=1}^{n} G_i 	imes \beta_i$$

Question 8

What is a key challenge in implementing PRS in precision medicine?

Accepted Answer

The need for a paradigm shift from binary genetic models to continuous risk models.

Question 9

In schizophrenia, what proportion of liability is explained by loci reaching genome-wide significance, and how does this change with more SNPs?

Accepted Answer

3.4% with significant loci, increasing to 7% with more SNPs included.

Question 10

Why is the PRS often standardized to have a mean of 0 and a standard deviation of 1?

Accepted Answer

To allow for easier comparison across individuals and to identify quantiles within the population.

Question 11

Which of the following statements about PRS and disease prediction is correct?

Accepted Answer

PRS distributions for cases and controls often overlap significantly, limiting predictive power.

Question 12

What is a practical implication of the PRS for individuals in the highest risk quantiles?

Accepted Answer

They may be offered earlier or more frequent screening and preventive interventions.

Question 13

Which of the following is a reason why PRS may be controversial in clinical practice?

Accepted Answer

Negative public attitudes towards genetic testing and the need for extensive clinician training.

Question 14

How might PRS be used in genetic counseling for individuals with high-risk CNVs?

Accepted Answer

To help estimate the additional risk conferred by common variants in combination with the CNV.

Question 15

Which of the following best explains why PRS is not yet widely used in clinical settings?

Accepted Answer

The proportion of variance explained by PRS is currently too low for most diseases.

Question 16

What is the main advantage of PRS over traditional rare variant genetic testing?

Accepted Answer

PRS provides a continuous measure of genetic liability, rather than a binary yes/no result.

Question 17

Which of the following is a correct interpretation of a PRS in the context of population risk?

Accepted Answer

Most individuals will have a PRS close to the population mean, indicating similar risk to the average population risk.

Question 18

Which of the following best describes the role of PRS in predicting prognosis for first episode psychosis?

Accepted Answer

PRS can help differentiate which patients are more likely to develop schizophrenia.

Question 19

What is a key reason for the limited predictive ability of PRS in non-European populations?

Accepted Answer

Differences in allele frequencies and linkage disequilibrium patterns compared to European populations.

Question 20

Which of the following strategies could improve the clinical utility of PRS?

Accepted Answer

Combining PRS with environmental risk factors and high-risk variants such as CNVs.

Polygenic Risk Scores and Their Application in Genetics and Medicine

Guida di studio - Domande di pratica