GlaxoSmithKline makes $300M investment in 23andMe, forms 50-50 R&D pact

so 23andme is like a unit test, and WGS is like the source code for the whole system

that said, we don't really know how to interpret most of the source code, so for a lot of cases (esp those that don't relate to medical treatment or research), 23andme is probably fine

It's shocking that so much genetic data is available, and we're barely scratching the surface, and using for fancy graphs and genealogy trees. We could be finding the cure for real diseases, and improving the lives of millions of people.

Yes, of course the pharma companies will milk the new drugs for the next couple of decades, until they lose the patent, yadda yadda, but at least we're making progress faster. Much better than the alternative - which is to wait decades for the discovery, AND wait more decades for the patents to expire...

Regarding privacy concerns, that's the least of my worries. The money available selling my genetic data (to, say, insurance companies), and the scrutiny and regulation they'd face (in many cases it'd be outright illegal - e.g., minors) is so massive that it'd be stupid to even try. There's a lot more money to be made from the exact same insurance companies by selling overpriced drugs to sick patients with health insurance.

In the spirit of not wanting to seem that way myself:

* here is a link to all of the clinical studies currently being conducted by glaxosmithkline: [0]. There are 4,662 studies currently listed. This is across dozens of countries. Click around and look at the data they are collecting (look at the endpoints, inclusion / exclusion criteria, etc). This is all clinical study data, so patients have to volunteer for this, but you also have to opt in to sharing your data for 23andme. I also know of a few companies that collected lab data from patients and sold them to pharma companies so they could target them with ads; patients had to opt in to this and there were privacy protections; I'd imagine there are plenty of other examples like this.

Also, thousands of other companies have access to massive amounts of health data, genetic and otherwise: EMR companies, insurance companies, hospitals, etc. Many of these groups share information with each other all the time, including genetic information. How else could a lab share with a hospital a patients sequence data? Why is this GSK / 23andme deal particularly concerning? Is it because 23andme or GSK are viewed as bad actors?

* here is a list of FDA approved nucleic acid based tests: [1]. More and more drugs are being approved to treat patients with specific genotypes, see slide 316 [2]

[0] https://clinicaltrials.gov/ct2/results?cond=&term=glaxo&cntr...

[1] https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedu...

[2] https://iabsverige.se/wp-content/uploads/InternetTrends2017R...

My argument: If you are exploring genomic datasets to find new potential drug targets, then what you really want as the output are single genes that are very strongly associated with dramatic phenotypes. Drugs generally only hit one molecule, so you want a monogenic vs polygenic signal, and drugs can't hit every molecule of a given type in the body, so you want a large effect size (if you only hit 10% of the target you still want a meaningful clinical effect)

If you don't have clinical data, your genetic data is Not super valuable for target discovery. You can't correlate genetics to clinical outcomes. The more clinical data you have, the more valuable your dataset, because you can uncover more gene-phenotype correlations. So you need high quality medical records, lab data, etc. if you just have self reported data on a few diseases, you'd miss all sorts of potentially useful signals

The type of genetic analysis is also super important. 23 and me does "genotyping": they have a chip with like 500k-1M molecular probes. Each probe is designed to detect a specific "SNP" mutation, i.e. A mutation where one DNA "letter" is different. So this doesn't pick up other non-SNP mutations but that's not as important. What's more important is that there are like 10M+ (edit: prev said 360M) known SNPs and prob a lot more unknown ones. So with 23andme you are only exploring a small part of the genome

And this part of the genome is fairly well explored. While next gen sequencing is a newer tech, gene chips (what 23andme uses) have been around longer. Most common mutations have been studied. And 23andme is just studying those common mutations but at a larger scale

However larger scale isn't necessarily that great for target discovery. With larger database you can pick up 1) more relationships with small effect size and 2) more rare relationships with large effect size. Except 23andme is using a gene chip that detects mostly common mutations, and bc they have limited clinical data they will mostly have common clinical condistion in their dataset. So you can really just pick up a lot of common mutations with significant but not meaningful relationship w outcomes

If you use exome sequencing like RGC, you get much richer coverage of the protein coding genome than 23andme. So you can pick up rare mutations. And you have more clinical data (arguably having more clinical data per genome is more valuable than having more genomes), so you can pick up more gene-phenotype relationships. You need to scale your sample set so you can detect rare mutations, but do you need 5M people? The more the better but RGC has already yielded some promising targets w it's smaller dataset

RGC is also smart and targeted about the kind of patients they recruit. So there is less noise and more signal, so you don't need as many patients. For example they look at fairly genetically homogenous "founder populations" that have less background genetic variability. Like the Icelandic population -- PCSK9 was discerned by analyzing this pop

PCSK9 gene is a classic example: mutations in this gene are very strongly associated with extreme levels of LDL cholesterol. And the relationship works for both gain of function mutations and loss of function mutations, and the causality can be validated experimentally.

The effect is dramatic: patients with loss of function mutations in PSCK9 have like 10% of the normal level of LDL cholesterol

And it's a monogenic trait: you can get these extreme LDL levels just by modifying PCSK9

So this is a great target assuming you can design a molecule to "block" it (you can). You can create an antibody that can basically have the same effect as the mutation (keeping PCSK9 from doing its job) but on a smaller and less durable scale.

The drug worked at lowering LDL cholesterol. It has had mixed commercial success for a variety of reasons unrelated to its effectiveness of lowering cholesterol

So this was really the first drug discovered based on large scale genomics. Regeneron developed one of the two PCSK9 inhibitors on the market. They purpose-built RGC to find more of these

While adverse selection is undeniably a tricky problem, the underlying raison d'etre is pooled risk, to help individuals and families mitigate catastrophic losses. Maybe you're all right with the prospect of future analyses condemning to uninsurability folks with rare combinations of alleles that turn out to be strongly deleterious. To me, this seems like breaking the regulated semi-statis between insurers and insureds, and like breaking the social contract more generally.

This might or might not be an issue now (regardless of the place of residence), but laws can always be changed. And societies can always develop to be more totalitarist, even up to extremes, and it is not like the collected data just vanishes when things start to slide. (Case in point: IBM's Hollerith machines and population records)

I was very curious about 23andme and really wanted to try it. After some due diligence I concluded it is not worth it because of privacy and other implications going forward. It is not what they do today, since they don't hide the obvious sharing and datamining, so if one joins them it is through informed consent. My concern was rather what kind of systems and policies they enable eventually in the future, after the information gets sold/shared enough times to anyone who can pay enough. At this point there is no control anymore in how (and by whom) the data gets used.

> It shall be an unlawful employment practice for an employer-- (1) to fail or refuse to hire, or to discharge, any employee, or otherwise to discriminate against any employee with respect to the compensation, terms, conditions, or privileges of employment of the employee, because of genetic information with respect to the employee;

No job advertising protection there

NJ (LAD):

> It shall be an unlawful employment practice, or, as the case may be, an unlawful discrimination: a.For an employer, because of [..], genetic information, [..] to refuse to hire or employ or to bar or to discharge or require to retire, unless justified by lawful considerations other than age, from employment such individual or to discriminate against such individual in compensation or in terms, conditions or privileges of employment;

Nope, nothing there either about recruitment ads..

Paternity tests involve random ~50% of your dna. Sperm samples are generally contaminated and thus less clear cut. But, people’s relatives have been used in the past for these tests dropping the bar even further.

However, being related genetically is not enough. Some people have twin siblings they don’t know about pointing out being related is not nessisarily mean you know anything about the other person allowing for false positives even at 3,400cM.

Unlikely sure, but harm comes in many forms. Saying I can’t think of anything is a long way from saying it’s safe.

Suppose a male with red hair, green eyes, and AB+ blood actually has those traits they are just not enough to unlikely identify someone. Adding more genetic traits on it's own is not enough for example you have identical twin or even triplet separated at birth. The core issue is DNA marks are not independent though people often assume they are.

People who have serious disabilities should be supported by taxpayer funded programs, in my opinion.

US insurance companies use treatment guidelines issued by organizations like NCCN (oncology). If they stray too far, they get dinged for not meeting "medical necessity" requirements.

If anything, you're more likely to get an experimental cancer drug in the US than Europe since US insurance companies don't like bad press.