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DNA helix
The US Food and Drug Administration (FDA) has authorized marketing of 23andMe Personal Genome Service (PGS) Genetic Health Risk (GHR) tests for 10 medical conditions.
These are the first direct-to-consumer tests authorized by the FDA that provide information on an individual’s genetic predisposition to certain conditions, including factor XI deficiency, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary hemochromatosis, hereditary thrombophilia, and other conditions.
The GHR tests work by isolating DNA from a saliva sample, which is then tested for more than 500,000 genetic variants.
Consumers receive reports of the results, which tell them if they have an increased risk of developing any of the following 10 conditions.
Factor XI deficiency
The 23andMe PGS Genetic Health Risk Report for Factor XI Deficiency is indicated for reporting of the F283L, E117X, and IVS14+1G>A variants in the F11 gene.
This report describes if a person has a variant associated with factor XI deficiency and the potential for a higher risk of excessive bleeding following trauma or surgery, but it does not describe a person’s overall risk for excessive bleeding. This report is most relevant for people of Ashkenazi Jewish descent.
G6PD deficiency
The 23andMe PGS Genetic Health Risk Report for Glucose-6-Phosphate-Dehydrogenase Deficiency is indicated for reporting of the Val68Met variant in the G6PD gene.
This report describes if a person has a variant associated with G6PD deficiency and a higher risk for episodes of anemia, but it does not describe a person’s overall risk of developing anemia. This report is most relevant for people of African descent.
Hereditary hemochromatosis
The 23andMe PGS Genetic Health Risk Report for Hereditary Hemochromatosis is indicated for reporting of the C282Y and H63D variants in the HFE gene.
This report describes if a person has variants associated with hereditary hemochromatosis and a higher risk for iron overload, but it does not describe a person’s overall risk of developing iron overload. This report is most relevant for people of European descent.
Hereditary thrombophilia
The 23andMe PGS Genetic Health Risk Report for Hereditary Thrombophilia is indicated for reporting of the factor V Leiden variant in the F5 gene, as well as the prothrombin G20210A variant in the F2 gene.
This report describes if a person has variants associated with a higher risk of thrombosis, but it does not describe a person’s overall risk of developing thrombosis. This report is most relevant for people of European descent.
Alpha-1 antitrypsin deficiency (AATD)
The 23andMe PGS Genetic Health Risk Report for Alpha-I Antitrypsin Deficiency is indicated for reporting of the PI*Z and PI*S variants in the SERPINA1 gene.
This report describes if a person has variants associated with AATD and a higher risk for lung or liver disease, but it does not describe a person’s overall risk of developing lung or liver disease. This report is most relevant for people of European descent.
Celiac disease
The 23andMe PGS Genetic Health Risk Report for Celiac Disease is indicated for reporting of a variant in the HLA-DQ2.5 haplotype.
The report describes if a person has a haplotype associated with an increased risk of developing celiac disease, but it does not describe a person’s overall risk for developing celiac disease. This report is most relevant for people of European descent.
Early onset primary dystonia (DYT1/TOR1A-related)
The 23andMe PGS Genetic Health Risk Report for Early-Onset Primary Dystonia (DYT1/TOR1A-Related) is indicated for reporting of the deltaE302/303 variant in the DYT1 gene.
This report describes if a person has variants associated with a higher risk for early-onset primary dystonia, but it does not describe a person’s overall risk of developing dystonia. This report is most relevant for people of Ashkenazi Jewish descent.
Gaucher disease
The 23andMe PGS Genetic Health Risk Report for Gaucher Disease Type 1 is indicated for reporting of the N370S, 84GG, and V394L variants in the GBA gene.
This report describes if a person has variants associated with an increased risk for developing carrier status for Gaucher disease type 1 in adults. This report also describes if a result is associated with personal risk for developing symptoms of Gaucher disease type 1, but it does not describe a person’s overall risk of developing Gaucher disease type 1.
This test is most relevant for people of Ashkenazi Jewish descent.
Late-onset Alzheimer’s disease
The 23andMe PGS Genetic Health Risk Report for Late-onset Alzheimer’s Disease is indicated for reporting of the ε4 variant in the APOE gene.
The report describes if a person’s genetic result is associated with an increased risk of developing late-onset Alzheimer’s disease, but it does not describe a person’s overall risk of developing Alzheimer’s disease.
The ε4 variant included in this report is found and has been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent.
Parkinson’s disease
The 23andMe PGS Genetic Health Risk Report for Parkinson’s Disease is indicated for reporting of the G2019S variant in the LRRK2 gene and the N370S variant in the GBA gene.
The report describes if a person’s genetic result is associated with an increased risk of developing Parkinson’s disease, but it does not describe a person’s overall risk of developing Parkinson’s disease. The test is most relevant for people of European, Ashkenazi Jewish, and North African Berber descent.
Access to testing
23andMe, Inc. said it will release its first set of GHR tests—for hereditary thrombophilia, late-onset Alzheimer’s disease, Parkinson’s disease, alpha-1 antitrypsin deficiency, and Gaucher disease—this month. The remaining tests will follow.
New 23andMe Health + Ancestry Service customers in the US will have access to these tests. Current 23andMe customers will be notified directly regarding their eligibility.
About the marketing authorization
The FDA reviewed data for the 23andMe GHR tests through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device.
Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the tests’ accuracy, reliability, and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar GHR tests.
The FDA intends to exempt additional 23andMe GHR tests from premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible after a one-time FDA review.
Excluded from the current marketing authorization and any future, related exemption are GHR tests that function as diagnostic tests.
