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Nearby variants are highly correlated due to their spatial proximity, a phenomenon known as linkage disequilibrium. Therefore a dense array of SNP genotypes is

Nearby variants are highly correlated due to their spatial proximity, a phenomenon known as linkage disequilibrium. Therefore a dense array of SNP genotypes is often sufficient to make statistically accurate inferences about the portion of the genome you do not directly assay. I myself have used this strategy to estimate my risk for possessing the ApoE variants from my 23andme callset. Is this 100% accurate? Of course not; no medical diagnostic is. But it is accurate enough to be used as a screening procedure in a lot of cases.

Gatsky 9y ago
If you start off with an inaccurate screening test, you waste a lot of resources with follow up testing, not to mention the psychological impact with BRCA tests.
- hyperbovine 9y ago
  Define inaccurate. 23andme is arguing that their diagnostic is to within a fraction of a percent as accurate as the gold standard.
  - Gatsky 9y ago
    ...for the few SNPs that they actually test. A negative 23 test does not exclude BRCA mutation. To apply link disequilibrium as you brought up doesn't change that.
    - hyperbovine 9y ago
      The FNR for this test is comparable with Sanger. I guess I don't really see your point.
      - Gatsky 9y ago
        Your 1st point is something like "these tests are useful for screening, you can get information about unassayed regions using statistical genetics approaches". My point is that this is not useful, since screening tests need to have certain properties not provided by SNP tests. The biggest issue is that 23andMe do not test the whole gene. This is like only doing a mammogram on one tenth of only the left breast, obviously a futile screening endeavour even if the FNR for that 10th is gold standard level. But most of all, unlike other screening tests which are designed to help the patient as much as possible (within societal resource constraints), 23andMe are offering a very limited test because that is what suits them, that is all that is possible with the SNP arrays around which they have built their business model. My original post was highlighting that unlike what is suggested on the gushing press release, this is not actually a great moment for direct to consumer genetic testing. If they were really interested in helping screen for BRCA mutations, 23andMe could swap out some of the other genes which tell you trivial stuff like how fast you metabolise caffeine, or some rare drug metabolism effect and include more BRCA SNPs. But they don't, because it is all about how many tests they sell and how useful the information is to pharmaceutical companies.

Gatsky 9y ago

If you start off with an inaccurate screening test, you waste a lot of resources with follow up testing, not to mention the psychological impact with BRCA tests.

hyperbovine 9y ago
Define inaccurate. 23andme is arguing that their diagnostic is to within a fraction of a percent as accurate as the gold standard.
- Gatsky 9y ago
  ...for the few SNPs that they actually test. A negative 23 test does not exclude BRCA mutation. To apply link disequilibrium as you brought up doesn't change that.
  - hyperbovine 9y ago
    The FNR for this test is comparable with Sanger. I guess I don't really see your point.
    - Gatsky 9y ago
      Your 1st point is something like "these tests are useful for screening, you can get information about unassayed regions using statistical genetics approaches". My point is that this is not useful, since screening tests need to have certain properties not provided by SNP tests. The biggest issue is that 23andMe do not test the whole gene. This is like only doing a mammogram on one tenth of only the left breast, obviously a futile screening endeavour even if the FNR for that 10th is gold standard level. But most of all, unlike other screening tests which are designed to help the patient as much as possible (within societal resource constraints), 23andMe are offering a very limited test because that is what suits them, that is all that is possible with the SNP arrays around which they have built their business model. My original post was highlighting that unlike what is suggested on the gushing press release, this is not actually a great moment for direct to consumer genetic testing. If they were really interested in helping screen for BRCA mutations, 23andMe could swap out some of the other genes which tell you trivial stuff like how fast you metabolise caffeine, or some rare drug metabolism effect and include more BRCA SNPs. But they don't, because it is all about how many tests they sell and how useful the information is to pharmaceutical companies.