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3/14/19
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Direct-To-Consumer Testing: What You Need to Know
Kate Principe, MS CGCCertified Genetic Counselor
Regional Genetics Coordinator, Gulf CoastTexas Oncology
I have no financial disclosures
I will be discussing various laboratories and genetic testing products. Statement should not be
considered an endorsement of a specific laboratory.
I have not personally used any DTC products
Learning Objectives
Genetics 101
Credit: Myriad Genetics
The Central Dogma
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The Human Genome Types of Genetic Changes
Single Nucleotide Polymorphisms• “SNP”• Substitution of 1 base pair for another
• 2 or more versions of a sequence
• Used as markers for genetic disease / trait
•May not be causative!•May not impact protein function!
• COMMON!•Occurs in >1% of the general population•~10 million total SNPs in human genome
Pathogenic Variants • “Mutation”•DNA change that causes disease / increases risk
•Multiple types of mutations (large del/dup, single base pair change, etc• Affects protein function
• RARE!•Occurs in <1% of general population
1.1
1.5
2.0
10.0
0.1 1.0 10.0 30.0
Minor Allele Frequency (%)Log scale
Relative Risk (OR)
Log scaleTP53
PTEN
CDH1
STK11
BRCA1BRCA2
BRIP1PALB2
ATMCHEK2
TNCR9
6q*
MAP3K1
FGFR2
CASP8LSP1
2q
8q
FGFX
Rare to very rare, high-risk alleles
Rare, moderate-risk alleles
Common, individually lower-risk alleles
* 6q effects apparently limited to Ashkenazi Jewish populationChart from Foulkes, NEJM, November 18, 2008
Highly penetrant. If an allele is highly penetrant, then the trait it produces will almost always be apparent in an individual carrying the allele.
Low penetrance. An allele with low penetrance will only sometimes produce the symptom or trait with which it has been associated at a detectable level. In cases of low penetrance, it is difficult to distinguish environmental from genetic factors.
Credit: Mary Freivogel MS CGC
Type of Genetic Testing
Genotyping• Evaluates common mutations / variations associated / linked to a disease or trait
• Looks at SNPs ONLY
Sequencing• Full gene analysis for many different types of mutations• Typically done in combination w/other testing modalities (del/dup, etc)
•More thorough, but potential to uncover unknown significance results
Possible Results
Genotyping• SNP is present
• 1 copy• 2 copies
• SNP is absent
Sequencing• Positive• Negative• Variant of Uncertain Significance
Types of Genetic Testing
Direct to Consumer (DTC) Testing
• Initiated by consumer
• No MD / clinician involved
• Genotyping for SNPs
• Self pay• Ancestry, health
trait, entertainment-ome
Patient Initiated Testing
• Patient initiated• Doctor approved*• Full genetic
analysis• Self pay or
insurance• Cancer panels,
carrier screening, pharmacogenetics
Provider Initiated Testing
• Provider recommends and coordinates testing
• Diagnostic testing• Insurance (when
criteria are met)• Hereditary cancer
risk panels, cardiac, neurologic, etc
Credit: Andrea Forman MS CGC
* Doctor may be employed / contracted by lab
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Types of Genetic Testing
• Ancestry(composition, haplogroups, DNA relatives)
• Traits (hair color, ear wax type)
• Paternity/relationship• Other (wine
preference)
• Carrier screening• Pharmacogenomics• Hereditary cancer• Adult onset disease
(Mendelian and multifactorial)
• Nutrigenomics (diet, supplementation)
• Sports/fitness (performance, injury)
• WGS/WES (healthy population)
• Skin (wrinkling, irritation, sun damage)
• Telomere length
Non-health related Health related
Credit: Mary Freivogel MS CGC
At Home genetic Tests
(health testing only)
DTC Patient initiated
There’s (apparently) a test for that!
Ancestry Testing
Ancestry Testing
•Methodology• Y chromosome testing•Mitochondrial DNA testing• SNP (preferred and more common method)
• Evaluate a large number of SNPs across a genome, compare results to reference panel to estimate someone’s ethnic background• Reference panel: people who have done testing previously, people with known ancestry, publicly available DNA databases
https://ghr.nlm.nih.gov/primer/dtcgenetictesting/ancestrytesting
Ancestry Testing
• Limitations• Human migration patterns• Reference panels differ from lab to lab
https://ghr.nlm.nih.gov/primer/dtcgenetictesting/ancestrytesting
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Ancestry Testing
• Considerations• Cultural ancestry vs. genetic ancestry• Family secrets
Ancestry Testing in the News
Health Testing
23andMe
Can opt out of genetic risk report
www.23andme.com
23andMe: BRCA
www.23andme.comwww.23andme.com
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23andMe: BRCA
• 1/40 individuals of Ashkenazi Jewish ancestry will have 1 of these 3 BRCA1/2 mutations
•>1800 BRCA1/2 variants and counting…
•What about other breast and ovarian cancer genes????
23andMe: Social Media
Credit: Andrea Forman MS CGC
23andMe: Future Testing
•Will assess 2 common genetic variants in MUTYH gene• c.536A>G, c.1187G>A
• 1-2% of general population carries 1 MUTYH mutation• Slight increase in colon cancer risk
• If you carry 2 MUTYH mutations: MUTYH-associated polyposis• 70-100% colon cancer risk
•What about other colon cancer genes????
www.23andme.com
REMEMBER: Most disease risk is multifactorial!
23andMe
www.23andme.com
23andMe
= ACOG www.23andme.com
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23andMe
www.23andme.com
23andMe
What’s missing?• Spinal muscular atrophy• Alpha thalassemia• Fanconi anemia group A• Fanconi anemia group C• Joubert disease
www.23andme.com
Genopalate
• 104 SNPs related to how the body processes food•Metabolism• Absorption
• Results:• Recommended intake level of 26 nutrients•Gluten and lactose sensitivity• Caffeine and alcohol metabolic rate• “Your Foods”
• Comprehensive food list that have nutrients you will benefit from the most, based on your DNA
www.genopalate.com
Considerations…
www.23andme.com
Considerations…
80% agree to participate in research
www.23andme.com
Considerations…
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Ethical Considerations
• No minimum ordering age…• Parents can order a 23andMe health trait kit for their children
The “Entertainment-ome”(phrase coined by Scott Weissmann, MS CGC)
23andMe
www.23andme.com
Raw Data
Raw Data
•DTC companies only analyze SNPs that are VALIDATED•May analyze >600,000 SNPs in total, but report on only a fraction
• Some DTC companies will give you the option to download your raw data • FOR RESEARCH, EDUCATIONAL, AND RECREATIONAL PURPOSES ONLY
3rd party interpretation tools
• Promethease• Runs raw data through SNPedia.com
• Enlis Genetics• Software to analyze SNP data
•Genetic Genie•Methylation and detox analysis
• XCode Life• “Tailored” diet and exercise plans, allergies, skin care recs
• Stratagene•MTHFR and “epigenetic analysis”
PSEUDOSCIENCE
Credit: Andrea Forman MS CGC
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Raw Data
Credit: Erynn Gordon MS CGC
Raw Data
www.Promethease.com
Raw Data
www.promethease.com; Ancestry.com Sample1 test patient
Pitfalls of Raw Data
43 variants sent for testing
17/43: false positive
8/43: confirmed, but classified inaccurately (pathogenic by raw data, benign or VUS by clinical lab)
Pitfalls of Raw Data
Tandy-Connor et al., 2018
Pitfalls of Raw Data
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My patient brought me their DTC results… NOW WHAT?!
Questions to ask
(1) Motivations•What motivated the patient to undergo at home genetic testing / assess their raw data?• Are there specific health conditions the patient is concerned about?• Before testing? After testing?
(2) Personal and Family History• Are there health conditions the patient may be at increased risk for, based on personal or family history?
(3) REFER to a genetics professional
Credit: Lisa Madlensky, PhD, CGC
Genetic Counseling for DTC
** Most in-person genetic counselors will not see a patient just for DTC results review **
If there is…• Raw data that needs clinical confirmation• Personal/family history that warrants additional work up
Send the patient to a local genetic counselor
Genetic Counseling for DTC
DTC is everywhere…
www.amazon.com, searched: “Genetic testing”
