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Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.

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Resources for Genetics Professionals — Direct-to-Consumer Genetic Testing

Synonyms: DTC Genetic testing, Direct Access Genetic Testing, Consumer-Initiated Genetic Testing, Patient-Directed Genetic Testing

, MD and , PhD.

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Estimated reading time: 5 minutes

Definition

Genetic testing provided by commercial laboratories directly to consumers without requiring an order by a health care professional or authorization for payment by a third-party payer. The results of DTC testing are not included in the medical record unless requested by the consumer.

Advantages

DTC genetic testing:

  • Increases consumer access to genetic testing as it does not need to be ordered by a health care professional and payment does not need to be authorized by a third-party payer (e.g., it may enable consumer to participate in clinical trials that require molecular confirmation of a clinical diagnosis).
  • Increases consumer autonomy regarding identification of risk for genetic disease(s).
  • Allows the consumer the opportunity to maintain privacy of genetic test results, as results are only included in medical records at the request of the consumer.
  • May be more affordable than tests ordered by a health care provider and not covered by a third-party payer.

Disadvantages

With DTC genetic testing:

  • The consumer may not understand test limitations. For example, test sensitivity, specificity, positive predictive value, and negative predictive value may not be easily accessible or interpreted correctly by the consumer.
  • Consumers may be more susceptible to deceptive/misleading marketing practices than health care providers familiar with the limitations of genetic testing.
  • The consumer does not benefit from health care provider identification and selection of appropriate testing.
  • The consumer may not have the benefit of pretest genetic counseling describing risks and benefits of testing.
  • The consumer may not have the benefit of discussion of test results with qualified genetics professional including post-test genetic counseling.
  • Disclosure of genetic risk can change physiology and increase the risk of disease independent of genetic risk factors. For example, in one study, measures of endurance and satiety were affected by perceived genetic risk more than actual genetic risk [Turnwald et al 2019].
  • Cost of testing is the responsibility of the consumer without the option of insurance coverage by a third-party payer.

Test Methods Used in DTC Genetic Testing

For general predictions about health

  • Targeted sequencing of SNPs (single-nucleotide polymorphic sites) at which a specific allele has been associated with a low or high risk for a specific phenotype (e.g., LRP5 p.Ala1330Val SNP associated with decreased bone density)
  • Targeted sequencing of variants associated with specific traits (e.g., ADH1B variants affecting alcohol metabolism)

For risk information for specific diseases

  • Targeted sequencing of a panel of known pathogenic variants associated with specific genetic disorders
  • Targeted sequencing of variants associated with an increased risk for a genetic disorder (e.g., HLA-DQA1 and HLA-DQB1 variants associated with an increased risk of celiac disease)

For risk information for a wide variety of genetic disorders

  • Exome sequencing to identify coding pathogenic variants associated with specific genetic diseases and SNPs associated with disease risk (see Genetic Testing: Current Approaches, Exome Sequencing)
  • Genome sequencing to identify coding and noncoding pathogenic variants associated with specific genetic diseases and SNPs associated with disease risk (see Genetic Testing: Current Approaches, Genome Sequencing)

For carrier status for specific pathogenic variants

Targeted sequencing panels include pathogenic variants known to be associated with specific autosomal recessive and X-linked disorders; panels may be designed for individuals of a specific ethnicity to include pathogenic variants more common in individuals of that ethnicity.

Paternity/maternity testing

15-20 polymorphic short tandem repeats (STRs) are analyzed for repeat size at each allele and compared with the offspring’s sample. Sensitivity is based on the degree of polymorphism for each STR, the number of STRs analyzed, and the availability of one confirmed parent. Positive predictive value is typically >99%; negative predictive value is up to 100% [El-Alfy & Abd El-Hafez 2012].

Additional requirements for sample processing include photo identification at the time of sample collection and recording chain-of-custody of samples through the testing process.

Ancestry testing

Ancestry testing methods can include analyzing autosomal DNA (nuclear DNA from autosomes 1-22) and X chromosome DNA, Y chromosome DNA, and/or mitochondrial DNA. This analysis compares sequence variants (differences from reference sequence, typically SNPs) in an individual with frequencies and patterns of variation either in other individuals or in other populations.

  • Autosomal and X chromosome DNA tests can be used to identify relatives and predict ancestry. Testing infers ancestry by determining the proband’s genotype at approximately 700,000 SNPs on chromosomes 1-22 and X.
    • Identification of relatives. The proband’s genotypes at individual SNPs are compared with genotypes from other individuals in the laboratory’s database. Closely related individuals share a larger number of consecutive SNPs than more distantly related individuals. . Positive predictive value is highest in closely related individuals.
    • Ancestry predictions compare frequencies and patterns of SNPs reported in individuals of specific ethnicities (divided into 20-25 global regions) to infer ancestry. Sensitivity depends on the data available (i.e., the number of individuals tested and their ethnicity) in the database of the commercial laboratory and the relevance of modern populations to historic populations.
  • Y chromosome DNA tests can identify the relatives of a male who are related through a direct line of male ancestors. The genotype at 20,000-35,000 SNPs and length of multiple STRs is identified, the proband’s SNPs and STRs can be compared with SNPs and STRs from other males in the laboratory database. Closely related males share a larger number of consecutive SNPs and STRs than unrelated males. Because Y chromosome DNA evolves more slowly than autosomal DNA, more distantly related males will share longer segments of Y chromosome DNA than autosomal DNA.
  • Mitochondrial DNA tests can identify individuals who are related through a direct line of female ancestors (because mitochondrial DNA is inherited in males and females only from their mother). Test methods include sequencing two hypervariable regions in the mitochondrial genome and sequencing the entire mitochondrial genome. The proband’s sequence is compared to the Cambridge Reference Sequence and base pair differences between the proband and the reference sequence are reported. Because mitochondrial DNA evolves more slowly than nuclear (autosomal, X and Y chromosome) DNA, distantly related individuals will share more sequence variants identified in mitochondrial DNA than sequence variants identified in nuclear DNA (i.e., DNA from any of the 23 pairs of chromosomes).

Testing for personal (non-medical) information

Testing for personal (non-medical) information involves targeted sequencing of variants that are associated with specific phenotypic traits (e.g., taste preference, personality traits).

Regulation of DTC Genetic Testing in the United States

The US Food and Drug Administration (FDA) regulates medical testing intended to provide a diagnosis or guide a patient’s treatment.

To date, two states in the US limit DTC testing:

  • Maryland allows only authorized health care professionals to order laboratory tests except those designated as over-the-counter testing by the FDA (e.g., home pregnancy test, blood glucose test).
  • New York state only allows DTC testing approved by the FDA (e.g., 23andMe)

Companies that offer tests for health assessment must use laboratories that are CAP (College of American Pathologists) certified and CLIA (Clinical Laboratory Improvement Amendments) certified.

Note: CLIA authorizes regulation of laboratories that conduct testing on human specimens for health assessment. The intent is to ensure accurate, reliable, timely testing. Topics beyond the scope of CLIA regulations include clinical validity, DTC claims, requirements for consent for testing and pre-test and/or post-test counseling, and any tests that do not assess health.

Companies that offer tests for other purposes (e.g., general predictions about health, entertainment, ancestry) are not required to use CAP- or CLIA-certified laboratories .

References

  • El-Alfy SH, Abd El-Hafez AF. Paternity testing and forensic DNA typing by multiplex STR analysis using ABI PRISM 310 Genetic Analyzer. J Genet Eng Biotechnol. 2012;1:101-12. Available online. Accessed 6-11-19.
  • Turnwald BP, Goyer JP, Boles DZ, Silder A, Delp SL, Crum AJ. Learning one's genetic risk changes physiology independent of actual genetic risk. Nat Hum Behav. 2019;3:48–56. [PubMed: 30932047]
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Bookshelf ID: NBK542335

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