Genomics in general practice

Genetic tests and technologies

Personal genomic testing

Personal genomic testing

PRACTICE POINT

At this time, the clinical utility of personal genomic testing, or online DNA testing, is considered variable and depends on the specific variants that are reported. If patients wish to pursue testing, ensure they opt for a full-service provider that includes the need for referral by a general practitioner (GP), test interpretation and genetic counselling support.

What is personal genomics?

With the advancement of gene sequencing technology, genetic testing is increasingly moving beyond the clinic and tertiary medical centres, and into the community. This new form of testing is readily accessible via the internet, either through a health practitioner or by individuals themselves, and represents the new world of personal genomic testing.

Clinical genetic testing has traditionally been used to gather information or confirm a diagnosis of a condition in an individual showing symptoms. Testing has also been used to screen asymptomatic populations, such as  carrier screening Carrier screening is a test to determine whether an individual carries a genetic variant that does not generally affect that individual’s health, but increases his or her chance of having children with the condition in question. The outcome of such testing can influence future reproductive decisions. Carrier screening is performed on individuals who are not necessarily known to be at increased risk for a particular genetic condition. Screening tests can be conducted on individuals from specific groups such as those from a common ethnic background (eg: screening for Tay-Sachs disease carrier status in the Ashkenazi Jewish community) or entire populations. for recessive conditions. Until recently, these genetic tests have been targeted, looking for particular gene variants Gene variants are small DNA sequence changes (ie additions, duplications, deletions, substitutions). These variants can have a range of effects: some may cause disease (pathogenic variant), while others do not cause disease but may modify an individual’s risk of disease (i.e may increase risk or provide a protective effect). The vast majority of gene variants are benign and do not result in disease but rather contribute to the differences between people.  (or mutations) in specific genes. Clinical support, including genetic counselling, has generally been available to help individuals interpret and manage genetic test results.

However, new technology (eg single nucleotide polymorphism A nucleotide is a single base pair unit of DNA. A single nucleotide polymorphism (SNP or ‘snip’) or single nucleotide variant (SNV) is a variation in a single nucleotide occurring at a particular site in the genome. For example, one individual may have a ‘G’ at a particular location and another individual a ‘T’. If two or more alternative DNA variants occur at a particular location at a population frequency of >1%, it is defined as a SNP or SNV. SNPs/SNVs are the most common type of genetic variation in the human genome and account for approximately 0.02% of the genome.  [SNP] genotyping Genotyping (also known as genomic profiling or genomic scanning) is a test to determine an individual’s single nucleotide polymorphism (SNP) profile. A SNP profile may be used to predict disease susceptibility by calculating polygenic risk scores, tailor treatment based on pharmacogenomic variants, or provide non– health related information (eg paternity, ancestry).Currently polygenic risk score may only be useful for people of European ancestry as there are not yet enough data available to reliably apply them to non-European populations. ) can now examine thousands of gene varaints Gene variants are small DNA sequence changes (ie additions, duplications, deletions, substitutions). These variants can have a range of effects: some may cause disease (pathogenic variant), while others do not cause disease but may modify an individual’s risk of disease (i.e may increase risk or provide a protective effect). The vast majority of gene variants are benign and do not result in disease but rather contribute to the differences between people. throughout a person’s genome. The genome is the entire set of genetic material, including all coding and non-coding DNA.

New sequencing technology also allows the entire sequencing of an individual genome (whole genome sequencing) at a relatively low cost. The availability of such technology is challenging the traditional model of genetic testing.
 
Asymptomatic individuals now have the opportunity to access ‘direct-to-consumer’ (DTC), ‘at-home’ testing, or ‘online DNA testing’, through a range of private providers.
 
Some DTC companies require a health practitioner to order a test on behalf of the consumer and take delivery of the test results, while others do not. A test kit provided by the DTC company is used to collect a cheek swab or saliva sample and mailed back for analysis. In some cases, results are returned to the consumer without comprehensive interpretation and/or clinical support.
 
While personal genomic testing has predominantly been offered as a direct-to-consumer service through international companies, in Australia clinicians can order certain types of personal genomic test for their patients through commercial laboratories. This includes panels for carrier screening for autosomal recessive conditions, pharmacogenomics and some polygenic risk scores (eg for certain cancers).

What do I need to know?

Personal genomic testing refers to the analysis of some or all of a person’s genome. Personal genomic testing is marketed for a variety of purposes, including:

  • identification of susceptibility to a wide range of diseases using polygenic risk scores
  • carrier screening Carrier screening is a test to determine whether an individual carries a genetic variant that does not generally affect that individual’s health, but increases his or her chance of having children with the condition in question. The outcome of such testing can influence future reproductive decisions. Carrier screening is performed on individuals who are not necessarily known to be at increased risk for a particular genetic condition. Screening tests can be conducted on individuals from specific groups such as those from a common ethnic background (eg: screening for Tay-Sachs disease carrier status in the Ashkenazi Jewish community) or entire populations.  for autosomal recessive conditions
  • pharmacogenomics
  • nutrigenomics (ie diet, nutrition, wellness)
  • fitness and sporting abilities
  • ancestry
  • relationship (eg paternity) testing

The cost of personal genomic testing varies according to the type of test (eg SNP Single nucleotide polymorphism/single nucleotide variant A nucleotide is a single base pair unit of DNA. A single nucleotide polymorphism (SNP or ‘snip’) or single nucleotide variant (SNV) is a variation in a single nucleotide occurring at a particular site in the genome. For example, one individual may have a ‘G’ at a particular location and another individual a ‘T’. If two or more alternative DNA variants occur at a particular location at a population frequency of >1%, it is defined as a SNP or SNV. SNPs/SNVs are the most common type of genetic variation in the human genome and account for approximately 0.02% of the genome. genotyping Genotyping (also known as genomic profiling or genomic scanning) is a test to determine an individual’s single nucleotide polymorphism (SNP) profile. A SNP profile may be used to predict disease susceptibility by calculating polygenic risk scores, tailor treatment based on pharmacogenomic variants, or provide non– health related information (eg paternity, ancestry).Currently polygenic risk score may only be useful for people of European ancestry as there are not yet enough data available to reliably apply them to non-European populations. exome sequencing The exome is the part of the genome that contains protein-coding genes only. The exome represents less than 2% of the genome, but contains about 85% of known disease-causing gene variants. , whole genome sequencing ) and how much information is provided with the results. Personal genomic testing is not funded by the Medicare Benefits Schedule (MBS), so consumers incur the full cost.
 
Personal genomic testing results may be provided with some clinical interpretation in the form of follow-up genetic counselling or a written report, or as raw sequence data. In some situations, the consumer is left to interpret the results without clinical guidance. This can prompt the individual to contact their GP for additional support. Referral of all such patients to public genetics services for assistance is not practicable given the resource implications.

What is tested? 

Personal genomic testing can provide information that is health or non-health related. Non-health related information includes:
  • physical traits (eg red hair, freckles)
  • genetic relationship testing (eg paternity testing)
  • ancestry
Some tests offer information that have health-related implications to varying degrees. In some cases, the tests are the same as those offered in regular clinical settings. Personal genomic tests might include genetic variants that:
  • are associated with high risk for disease with greater certainty (eg BRCA1, familial breast and ovarian cancer)
  • are associated with a wide range of disease risks with variable levels of evidence (eg polygenic risk scores for cancers, heart disease)
  • are limited predictors of disease (eg APO-ε4, Alzheimer disease)
  • identify carrier status for recessive conditions (eg cystic fibrosis)
  • can inform response to drugs (refer to ‘Pharmacogenomics’ ).
Some companies test for variants for other health-related information that are more uncertain, such as variants with low penetrance Penetrance refers to the proportion of people with a particular genetic variant who will go on to develop the condition. For example, people carrying an autosomal dominant variant may not always develop the condition – this is called ‘incomplete penetrance’. If a condition is 100% penetrant, an individual will definitely develop the condition. If penetrance is 80%, most but not all individuals will develop the condition. Other genes and lifestyle factors, such as diet, exercise and smoker status, may affect the penetrance of some conditions. , or with limited evidence to support associations with disease. These tests might include genetic variants that are:
  • marketed to predict sporting ability, including fitness and response to training regimens
  • professed to provide information about response to diet and nutrition (nutritional genomics) or weight loss (eg MTHFR gene testing). In Australia, these tests are advertised as ‘genomic wellness’ tests, and are increasingly available through naturopaths and nutritionists.

How do I manage personal genomic testing in general practice?

Advising patients who want personal genomic testing

Patients may ask a GP to order personal genomic testing on their behalf. GPs asked to arrange personal genomic testing should consider the following:

  • How much does the patient understand about the test?
  • What do they want to find out from the test and what will they do with that information?
  • Has the patient thought about the possible impact of testing on life insurance? (Refer to ‘Ethical principles’)
  • Will the company help interpret the results?
  • Do you feel able to assist the patient in interpreting results?

Managing patients who have had personal genomic testing

Patients who have already had personal genomic testing might ask a GP for:

  • help in interpreting the results
  • further testing
  • advice around treatment or management 

The majority of patients will have small variations in risks for a range of conditions, which will have limited clinical implications. In these circumstances, general preventive health advice is appropriate.

In a minority of patients, specific variants that put an individual at significantly increased risk of a condition (eg BRCA gene mutations, HFE-haemochromatosis, macular degeneration) will be identified. In these situations, referral to genetics or specialist services is appropriate.

Implications for general practice

The uptake of personal genomic testing is likely to continue, and GPs will increasingly encounter patients who are curious about or have used personal genomic testing.

Commercial companies may begin to promote personal genomic testing to GPs, especially as the evidence builds for the clinical validity and utility of some components of these tests. 

Some personal genomic testing companies recommend using specific practitioners (ie those they nominate who may have undertaken some training) who will order the test on behalf of the consumer. Some of these companies may also provide genetic counsellors who can discuss the results with the consumer.

Other companies state that the personal genomic testing reports are provided for information or educational purposes only. They may state that the consumer should talk to their GP or other health practitioners about their results. However, practitioners themselves may have a limited understanding of the nature of the test or its interpretation.

The National Health and Medical Research Council (NHMRC) has developed a personal genomic testing resource entitled ‘Understanding direct-to-consumer (DTC) genetic DNA testing: An information resource for consumers’. GPs can use this document to discuss personal genomic testing with patients who are interested in ordering a test.

Further reading

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