Friday, August 15, 2014

Why bother with 23andMe?

The genetics company 23andMe is no longer permitted (under a current US FDA ruling) to provide you with health advice based on sequencing your own DNA sample. In practice this is not an issue since you simply go to Promethease and import to them your raw data from 23andMe (as described here). For some reason this is not forbidden.

How useful are these reports? To be honest, I believe they're of bounded interest, and here's why.
"A number of commercial firms offer targeted or extensive genotyping to anyone who wants to submit a saliva specimen and pay a fee. Some of the reasons suggested for doing this include identification of ancestral background, relationship certification and most commonly, detection of genetic susceptibilities to disease.

"The latter are almost entirely based on GWAS that have associated specific single nucleotide polymorphisms (SNP) with an increased (or decreased) likelihood of developing a particular common disease. In almost all such GWAS-based analyses, the association with disease is highly statistically significant but of remarkably little predictive value. In other words, the relative risks of developing a disease based on having one of these markers is typically in the range of 1.1–1.4.

"Moreover, virtually no research has been done to examine the clinical utility of being identified as having one of these risk markers. For example, is someone with the 9p21-linked SNP that has no known biologic function but is associated with a slightly greater risk of developing an atherosclerosis-related condition more likely to alter their lifestyle, change their diet, or stop smoking? "
In addition, there are many other sources of error in the genetic code which can have profound medical implications - but are not SNPs - such as (from the same report):
"Translocation results from an exchange of parts of two chromosomes.

"Deletion is loss of chromosomal material.

"Duplication is the presence of two or more copies of the same region of a given chromosome. The redundancy may occur in the same chromosome or in a nonhomologous chromosome. In the latter case, a translocation will also have occurred."
So most health reports tell you that you have some SNPs which increase, or decrease your susceptibility to this or that condition, but in the current state of the research it's not known how many other SNPs or distinct genetic modifications could also affect the likelihood of acquiring it. Early days indeed!

One of the things 23andMe ask you is whether you permit them to keep your sample for ten years (I guess in liquid nitrogen or something). I imagine that in a decade the cost of a complete genome sequencing will have come down to something affordable and 23andMe will then be able to offer a much more sophisticated analysis/diagnostic service based on your complete genome (FDA willing!).

Assuming we will also by then understand a lot more about how the genome ties in to phenotypic traits such as health, intelligence, personality, appearance, sports potential and so on, the report in 2024 might be quite informative, and the one in 2034 even more so.

One generation down-track from now, everyone will have their genome transcribed for health reasons, and moreover we'll understand it. One of our remote descendants may well be interested in their ancestors, bewailing the fact that they never got genotyped.

But wait!


Steve Hsu has more to say here:
"... given sufficient phenotype|genotype data, genomic prediction of traits such as cognitive ability will be possible. If, for example, 0.6 or 0.7 of total population variance is captured by the predictor, the accuracy will be roughly plus or minus half a standard deviation (e.g., a few cm of height, or 8 IQ points). The required sample size to extract a model of this accuracy is probably on the order of a million individuals. As genotyping costs continue to decline, it seems likely that we will reach this threshold within five years for easily acquired phenotypes like height (self-reported height is reasonably accurate), and perhaps within the next decade for more difficult phenotypes such as cognitive ability. At the time of this writing SNP genotyping costs are below $50 USD per individual, meaning that a single super-wealthy benefactor could independently fund a crash program for less than $100 million.

"Once predictive models are available, they can be used in reproductive applications, ranging from embryo selection (choosing which IVF zygote to implant) to active genetic editing (e.g., using powerful new CRISPR techniques). In the former case, parents choosing between 10 or so zygotes could improve their expected phenotype value by a population standard deviation. For typical parents, choosing the best out of 10 might mean the difference between a child who struggles in school, versus one who is able to complete a good college degree. Zygote genotyping from single cell extraction is already technically well developed, so the last remaining capability required for embryo selection is complex phenotype prediction. The cost of these procedures would be less than tuition at many private kindergartens, and of course the consequences will extend over a lifetime and beyond.

"The corresponding ethical issues are complex and deserve serious attention in what may be a relatively short interval before these capabilities become a reality. Each society will decide for itself where to draw the line on human genetic engineering, but we can expect a diversity of perspectives. Almost certainly, some countries will allow genetic engineering, thereby opening the door for global elites who can afford to travel for access to reproductive technology. As with most technologies, the rich and powerful will be the first beneficiaries. Eventually, though, I believe many countries will not only legalize human genetic engineering, but even make it a (voluntary) part of their national healthcare systems. The alternative would be inequality of a kind never before experienced in human history."