Do You Want Fries With That?- The Pros and Cons of Direct to
Consumer Genetic Testing ‘BigGene)cs’Sessions
Ma1hewTaylorMD,PhDDirectorAdultMedicalGene)csProgram,AssociateDirectorColoradoCenter
PersonalizedMedicine,UniversityofColorado
Disclosure Slide: Matthew Taylor (2018) I have financial ties that may (or may not) relate to the content of this
presentation that are disclosed to the University of Colorado:
• Allomek • American Board of Medical
Genetics and Genomics • American college of graduate
medical education (ACGME) • Arca Biopharma Inc. • Array Biopharma • Biomarin Pharmaceuticals, Inc. • CU Medicine
• GeneDx • Genzyme, a Sanofi Company • Guidepoint Global • Hershey Decker Drake • Inspired Opinions(Schelsinger) • Rocket Pharma • Valerion Therapeutics • Wellpoint
Per UCD Disclosure Policy: http://www.ucdenver.edu/academics/colleges/medicalschool/facultyAffairs/Documents/UCSOMFacultyFinancialDisclosuresResolution.pdf
Second Disclaimer • Severalcommercialcompanieswillbemen)onedinthispresenta)on
• Itisnotmyintenttoendorseornega)vecri)cizeanycompany(ies)
• IhavehadmyDNAanalyzedby23andMeandhavehadwholegenomesequencingcompletedbyIllumina
Do You Want Fries With That?-
The Pros and Cons of Direct to Consumer Genetic Testing
Session Objectives • DescribethecurrentDirecttoConsumer(DTC)Gene)cTes)nglandscape
• Evaluatetheposi)veaspectsofDTCGene)cTes)ng(bothpurportedandreal)
• Appraisethepoten)aldrawbacksandlimita)onsofDTCGene)cTes)ng
• ChoosehowyouwillapproachDTCGene4cTes4ngwithyourpa4ents(…Discussion)
Describe the current Direct to Consumer (DTC) Genetic Testing
landscape
Definition of Direct To Consumer (DTC) Testing
• Commercialgene)ctes)ngcompanies– ancestry,traits,diseaserisk,pharmacokine)cs,paternity
– ~Target‘common’,low/nonpenetrantvariants• Orderingprovider~notrequired• Pa)ent(consumer)driven:
– decideswhethertoshareresultswithproviders• $15M2010à$130M2015à$350M2020
Clinical vs. Direct To Consumer (DTC) ClinicalGene4cTes4ng
– Germlinemuta)on(s)suspected
– OrderedbyhealthproviderwithGenCounseling
– Resultssharedwithpa)ent– ‘Interpreted’byhealthprovider
DirectToConsumer– Specificmuta)onoZennotsuspected
– Purchasedbyconsumerw/ocounseling
– Resultsreceivedbyperson– Interpreta)onbylab/company/website
Some DNA testing companies • 23andMe)• 23mofang• 24gene)cs• AfricanAncestry• AfricanDNA• AncestrybyDNA• AncestryDNA,• AtlasBiomed• CentrillionBiosciences• DanteLabs• DNAAncestryandFamily
Origin• DNAConsultants• DNATribes• DNAWorldwide• FamilyTreeDNA)• FullGenomesCorpora)on• GenebyGene• Genebase
• GenoTek• GenographicProject• GenosResearchInc• Helix• iGENEA• LivingDNA• MyHeritageDNA• OxfordAncestors• RootsforReal• SorensonGenomics• SureGenomics• TribeCode• VeritasGene)cs• Xcode• WeGene• YSEQ• Yoogene
h1p://blog.ambrygen.com/ambry/post/185/direct-to-consumer-gene)c-tes)ng-taking-the-trend-to-the-next-level-responsibly
Timeline • 2010:>30companies,>400tests1
• 2011:AMAsendsle1ertoFDAsugges)ngthatallgene)ctes)nginvolveaphysician1
• 2013:FDAhalted23andMegene)chealthscreening
• 2015:FDAliZedban• 2017:FDAapprovedDTCgene)ctes)ng(23andMe;10diseases)
• 2018:FDAapprovedDTCgene)ctes)ng(23andMe;BRCA1/2)
1)Blossetal.HumanMolecularGene4cs,2011
23andMe Genetic Health Risk 2017FDAAPPROVED
• (2)Parkinson’sdisease(LRRK2,GBA)• (1)Late-onsetAlzheimer’s(APOE)• (2)Celiacdisease(HLA-DQB1&DQA1)• Early-onsetprimarydystonia• FactorXIdeficiency• Gaucherdiseasetype1• (2)Alpha-1an4trypsindeficiency
(SERPINA1)• (1)Glucose-6-Phosphate
Dehydrogenasedeficiency• (2)Hereditaryhemochromatosis(HFE:
C282Y,H63D))• (2)Hereditarythrombophilia,(FactorII
&V)
2018SEPTEMBER• X(2)Age-relatedmaculardegenera4on
(Y402H,A69S)• (3)BRCA1/2(185delAG,5382insC,6174delT)• Early-onsetprimarydystonia• FactorXIdeficiency• Gaucherdiseasetype1
h1ps://www.fda.gov/newsevents/newsroom/pressannouncements/ucm551185.htm h1ps://permalinks.23andme.com/pdf/PN-20-0279.pdf
Evaluate the positive aspects of DTC Genetic Testing (both
purported and real)
Arguments Favoring Value of DTC • Enhancesindividualautonomy/choice• Denyingaccessispaternalis)c
– Pa)entaccesstoolsexist(thermometers,BP&glucosemonitors,pregnancy&HIVtests,fecalblood)
• Righttoaccessone’sowngene)cinforma)on– Righttoprivacyforone’sowngene)cinforma)on
• Powertounderstanddiseaseriskscouldmo)vatepersonstoimprovetheirhealth
Patient / Consumer Comments • Ithinkthisistheearlystagesofthenewmedicalera…althoughinforma4onispreliminaryjustknowingaboutyourselfthingsyoudidn’tknowbeforeIthinkisamazing.Ijusthadmytestdonethisweekandlookingforwardtotheresults.
• Carlos
CDCGenomicsandHealthImpactBlog:DirecttoConsumerGene4cTes4ng:ThinkBeforeYouSpit,2017Edi4on!
Patient / Consumer Comments • Ireceivedhealthriskassessmentinforma4onfromaDTC
severalyearsagoandhavefounditquiteuseful.KnowingthatIwasathigherriskfor2DM,Ihavebeenmorecarefulofweightanddiet.KnowingthatIwasathigherriskformaculardegenera4on,I’venotskippedeyeexamina4onsandwon’t…It’sgoodtohavealltheinforma4onyoucanget.Medicalprofessionalswilljusthavetobebroughtintothemoderneraandquicklyandshouldnotignoreorresentitwhentheirpa4entsareknowledgeableaboutgene4cs.
• JeanCDCGenomicsandHealthImpactBlog:DirecttoConsumerGene4cTes4ng:ThinkBeforeYouSpit,2017Edi4on!
Appraise the potential drawbacks and limitations of DTC Genetic Testing
Arguments Concerning Risks of DTC • Areconsumerssufficientlyinformed/riskingmisinterpreta)on?• AretheDTCtestsallappropriate/havesufficientclinicalu)lity?
– Shouldresultswithlow-predic)ve-indicesbereported(GWASvariants)?
• Accuracyofresults(falseposi)vesandfalsenega)ves)– Unnecessaryworry/anxietyorinappropriatereassurance
• Inconsistent‘results’acrossdifferentDTCtests?• Whataretheprivacy/confiden)alityissues?
– Commercializa)on(saleofgene)cinforma)on/companiesbeingbought/sold)
Patient / Consumer Comments • TheaveragePCPdoesNOThaveenoughgene4ceduca4ontobeabletointerpretthetestresults.
MyPCP…didn’tunderstandenoughaboutgene4cstocorrectlyaccessmyhealthrisk
assessmentbaseduponfamilyhealth/medicalhistory.Myhighschoolgene4csfromCanada
turnedouttobemoregene4ceduca4onthenhereceivedinmedicalschool
• SheriCDCGenomicsandHealthImpactBlog:DirecttoConsumerGene4cTes4ng:ThinkBeforeYouSpit,2017Edi4on!
SaraAltschuledidDTCtes)ngforancestrypurposes.ReceivedemailaboutBRCA1/2tes)ngbeingnowavailable,chosetogetthoseresultsàlearnedshehadaBRCAmuta)on.Concerning,givenshehada
paternalcousin(once-removed)whohadbreastcanceranddiedofovariancancer.
IfyouwouldhavetoldmeatthebeginningofthisyearthatIwouldbewri)nga
columnonBRCA,Iwouldhavethoughtyou’dgotthewronggal.ButIliketothink
ofmyselfasa"glasshalffull"kindofperson.Andcurrently,myglassisfilledwithhope—hopethatI'mmaking
decisionsthatmayonedaysavemylife.
Dr.JoshClayton,a29year-oldradiologyresidentdidancestrytes)ng.Hethensubmi1ed
resultstoonlinehealthanalysiscompany,revealinghehadaLynchsyndromemuta)on.
SubsequentclinicalLynchsyndrometes)ngprovedtheoriginalresultswereafalse
posi)ve.
NYTimes
28 year-old woman DTC testing • Submi1edresultsfor3rd-partyanalysisàhomozygousforpathogenicCOL3A1(vascularEhlersDanlossyndrome)
• Previouslyseenbygene)csàhEDS– (normalechocardiogram;non-concerningfamilyhistory)
• RepeatclinicalsequencingofhEDSàhomozygousnormal
Ma1hewFenderdidDTC#1– (sisterdiedofpulmonary
embolism)àSentdatafor3rd-partyanalysisà
PSEN1pathogenicmuta)on
Mr.Fenderdiscussedwithhisdoctor
– anditwas“likehewasannoyedatme,”
DTC#2(holidayspecial)– noPSEN1muta)on
ClinicalPSEN1tes)ngànega)ve
62 year-old woman DTC testing • MDcontacteduswithcomment
– “…shehada[DTC]gene4ctestwhichsayssheisamale…Doyouhaveanyrecommenda4ons?
• DTCCompanyle[ertopa4ent– “Uponreviewofyourdata…itappearsourformulaclassifiedyoursex,basedonyourDNA,asmale…iftheresultsofouranalysisareunexpected,weencourageyoutoconsultyourphysicianoragene4ccounselor.
• ClinicaldiagnosisàAndrogenInsensi)vitySyndrome
Choose how you will approach DTC Genetic Testing with your
patients (…Discussion)
Do You Want Fries With That?- The Pros and Cons of Direct to
Consumer Genetic Testing ‘BigGene)cs’Sessions
Thankyouforyoura1en)[email protected]
