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
Stephanie E Wallace, MD and Lora JH Bean, PhD.
Author Information and AffiliationsInitial Posting: June 13, 2019.
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.
Purpose of DTC Genetic Testing
To provide:
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
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 historical 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. online Available. Accessed 10-24-22.
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. [
PMC free article: PMC6874306] [
PubMed: 30932047]
