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August 28, 2017

When journalists get out of their depth on genetic genealogy

Filed under: DTC personal genomics,Genealogy,Genetics,Personal genomics — Razib Khan @ 7:39 pm

For some reason The New York Times tasked Gina Kolata to cover genetic genealogy and its societal ramifications, With a Simple DNA Test, Family Histories Are Rewritten. The problem here is that to my knowledge Kolata doesn’t cover this as part of her beat, and so isn’t well equipped to write an accurate and in depth piece on the topic in relation to the science.

This is a general problem in journalism. I notice it most often when it comes to genetics (a topic I know a lot about for professional reasons) and the Middle East and Islam (topics I know a lot about because I’m interested in them). It’s unfortunate, but it has also made me a lot more skeptical of journalists whose track record I’m unfamiliar with.* To give a contrasting example, Christine Kenneally is a journalist without a background in genetics who nevertheless is immersed in genetic genealogy, so that she could have written this sort of piece without objection from the likes of me (she did write a book on the topic, The Invisible History of the Human Race: How DNA and History Shape Our Identities and Our Futures, which I had a small role in fact-checking).

What are the problems with the Kolata piece? I think the biggest issue is that she didn’t go in to test any particular proposition, and leaned on the wrong person for the science. She quotes Joe Pickrell, who knows this stuff like the back of his hand. But a more space is given to Jonathan Marks, an anthropologist who is quite opinionated and voluble, and so probably a “good source” for any journalist.

Marks seems well respected in anthropology from what I can tell, but he’s also the person who put up a picture of L. L. Cavalli-Sforza juxtaposed with a photo of Josef Mengele in the late 1990s during a presentation at Stanford. Perhaps this is why anthropologists respect him, I don’t know, but I do not like him because of his nasty tactics (I wouldn’t be surprised if Marks had power he would make sure people like me were put in political prison camps, his rhetoric is often so unhinged).

Marks’ quotes wouldn’t be much of an issue if Kolata could figure out when he’s making sense, and when he’s just bullshitting. But she can’t. For example:

…“tells me I’m 95 percent Ashkenazi Jewish and 5 percent Korean, is that really different from 100 percent Ashkenazi Jewish and zero percent Korean?”

The precise numbers offered by some testing services raise eyebrows among genetics researchers. “It’s all privatized science, and the algorithms are not generally available for peer review,” Dr. Marks said.

The part about precise numbers is an issue, though a lot less of an issue with high density SNP-chips (the real issue is sensitivity to reference population and other such parameters). But if a modern test says you are 95 percent Ashkenazi Jewish and 5 percent Korean it really is different from 100% Ashkenazi. Someone who comes up as 5% Korean against an Ashkenazi Jewish background is most definitely of some East Asian heritage. In the early 2000s with ancestrally informative markers and microsatellite based tests you’d get somewhat weird results like this, but with the methods used by the major DTC companies (and in academia) today these sorts of proportions are just not reported as false positives. Marks may not know because this isn’t his area, but Pickrell would have. Kolata probably did not think to double-check with him, but that’s because she isn’t able to smell out tendentious assertions. She has no feel for the science, and is flying blind.

Second, Marks notes that the science is privatized, and it isn’t totally open. But it’s just false that the algorithms are not generally available for peer review. All the details of the pipeline are not downloadable on GitHub, but the core ancestry estimation methods are well known. Eric Durand, who wrote the originally 23andMe ancestry composition methodology presented on it at ASHG 2013. I know because I was there during his session.

You can find a white paper for 23andMe’s method and Ancestry‘s. Not everything is as transparent as open science would dictate (though there are scientific papers and publications which also mask or hide elements which make reproducibility difficult), but most geneticists with domain experience can figure out what’s going on and it if it is legitimate. It is. The people who work at the major DTC companies often come out of academia, and are known to academic scientists. This isn’t blackbox voodoo science like “soccer genomics.”

Then Marks says this really weird thing:

“That’s why their ads always specify that this is for recreational purposes only: lawyer-speak for, ‘These results have no scientific standing.’”

Actually, it’s lawyer-speak for “do not sue us, as we aren’t providing you actionable information.” Perhaps I’m ignorant, but lawyers don’t get to define “scientific standing”.

The problem, which is real, is that the public is sometimes not entirely clear on what the science is saying. This is a problem of communication from the companies to the public. I’ve even been in scientific sessions where geneticists who don’t work in population genomics have weak intuition on what the results mean!

Earlier Kolata states:

Scientists simply do not have good data on the genetic characteristics of particular countries in, say, East Africa or East Asia. Even in more developed regions, distinguishing between Polish and, for instance, Russian heritage is inexact at best.

This is not totally true. We have good data now on China and Japan. Korea also has some data. Using haplotype-based methods you can do a lot of interesting things, including distinguish someone who is Polish from Russian. But these methods are computationally expensive and require lots of information on the reference samples (Living DNA does this for British people). The point is that the science is there. Reading this sort of article is just going to confuse people.

On the other hand a lot of Kolata’s piece is more human interest. The standard stuff about finding long lost relatives, or discovering your father isn’t your father. These are fine and not objectionable factually, though they’ve been done extensively before and elsewhere. I actually enjoyed the material in the second half of the piece, which had only a tenuous connection to scientific detail. I just wish these sorts of articles represented the science correctly.

Addendum: Just so you know, three journalists who regularly cover topics I can make strong judgments on, and are always pretty accurate: Carl Zimmer, Antonio Regalado, and Ewen Callaway.

* I don’t follow Kolata very closely, but to be frank I’ve heard from scientist friends long ago that she parachutes into topics, and gets a lot of things wrong. Though I can only speak on this particular piece.

June 16, 2017

The cultural revolution that will happen in China

Filed under: Baby Sequencing,DTC personal genomics,Veritas — Razib Khan @ 6:02 pm

If you’ve been hiding under a rock, please see Baby Genome Sequencing for Sale in China:

A Boston-based DNA sequencing company is offering to decode the complete genomes of newborns in China, leading some to ask how much parents should know about their children’s genes at birth.

Veritas Genetics says the test, ordered by a doctor, will report back on 950 serious early- and later-life disease risks, 200 genes connected to drug reactions, and more than 100 physical traits a child is likely to have.

Called myBabyGenome, the service costs $1,500 and could help identify serious hidden problems in newborns, the company says.

Obviously a $1,500 price point is beyond most Chinese. But the total fertility rate in China today is 1.56, and almost certainly lower among urban elites who could actually afford this service. Considering that genome is will you for life, more or less, $1,500 isn’t really that much.

For years there have been many fly by night genetics companies who have some presence in East Asia. They come and go. The combination of a lax regulatory environment and the allure of “genes” means that there is some money to be made. Veritas in contrast is a serious company. This is heralding the reality that widespread sequencing is going to go primetime.

Of course there is skepticism. Fortunately the piece doesn’t talk much to people who who express Leon Kass style FUD. The objections are scientific:

But some doctors say the plan is a huge overstep. “I think it’s vastly premature to peddle a completely unproven set of data, especially to a vulnerable population like neonates,” says Jim Evans, a professor of genetics at the University of North Carolina Chapel Hill.

The problem is that the risk posed by many disease genes remains uncertain. Even if a child has a mutation in a gene, he or she may never be affected, prompting debate among doctors about whether it’s useful to inform parents.

These are real objections, but I don’t see why sequencing should not be allowed as a choice by parents nevertheless. And widespread adoption of sequencing would actually allow us to start obtaining more data that we could use to make better decisions in the future. The genomics space for a while has had a bit of a chicken & egg problem. The sequencing is starting to get there, but we still need to get phenotypes. And this seems like one way to get the public involved and feel like they have a stake.

Like in vitro fertilization I see neonatal sequencing as inevitable in regards to whether it will be ubiquitous. It will be common. And “ethical problems” won’t really come up in the future because people will be comfortable with it. Right now there’s a fear factor.

This is in sharp contrast with CRISPR. That’s a technology that will have real consequences, and like male circumcision may be difficult to reverse for someone who as an adult was modified in infancy. In contrast a genome sequence is just more information.

For years may people have speculated that genetic testing technology will really begin to take off in Asia because for various reasons Americans and Europeans are wary. To me this is a signal that that might be occurring, depending on how successful Veritas’ venture is.

This is perhaps the most important point:
But Veritas will not reveal everything, in recognition that not all the information in the genome is appropriate to give parents right away. For instance, it won’t tell them about a gene that can strongly predispose people to Alzheimer’s in old age.

Instead, Veritas says, it will retain the rest of a newborn’s genome data and let parents purchase further information at a later date.

I think this may be more common than we think. Most people don’t want to deal with a ~3 GB text file. That being said, I think they should in the future have an option for people to buy their data outright.

Addendum: I met Robert Green at SxSW. Nice fellow. One thing that he mentioned was widespread opposition among physicians. I suspect one dynamic that MDs won’t like in the near future is decentralization of the distribution of medical services away from their own profession. This is part of it.

June 12, 2017

10 million DTC dense marker genotypes by end of 2017?


Today I got an email from 23andMe that they’d hit the 2 million customer mark. Since they reached their goal of 1 million kits purchased the company seems to have taken its foot off the pedal of customer base growth to focus on other things (in particular, how to get phenotypic data from those who have been genotyped). In contrast Ancestry has been growing at a faster rate of late. After talking to Spencer Wells (who was there at the beginning of the birth of this sector) we estimated that the direct-to-consumer genotyping kit business is now north of 5 million individuals served. Probably closer to 6 or 7 million, depending on the numbers you assume for the various companies (I’m counting autosomal only).

This pretty awesome. Each of these firm’s genotype in the range of 100,000 to 1 million variant markers, or single nucleotide base pairs. 20 years ago this would have been an incredible achievement, but today we’re all excited about long-read sequencing from Oxford Nanopore. SNP-chips are almost ho-hum.

But though sequencing is the cutting edge, the final frontier and terminal technology of reading your DNA code, genotyping in humans will be around for a while because of cost. At ASHG last year a medical geneticist was claiming price points in bulk for high density SNP-chips are in the range of the low tens of dollars per unit. A good high coverage genome sequence is still many times more expensive (perhaps an order of magnitude ore more depending on who you believe). It also can impose more data processing costs than a SNP-chip in my experience.

Here’s a slide from Spencer:

I suspect genotyping will go S-shaped before 2025 after explosive growth in genotyping. Some people will opt-out. A minority of the population, but a substantial proportion. At the other extreme of the preference distribution you will have those who will start getting sequenced. Researchers will begin talk about genotyping platforms like they talk about microarrays (yes, I know at places like the Broad they already talk about genotyping like that, but we can’t all be like the Broad!).

Here’s an article from 2007 on 23andMe in Wired. They’re excited about paying $1,000 genotyping services…the cost now of the cheapest high quality (30x) whole genome sequences. Though 23andMe has a higher price point for its medical services, many of the companies are pushing their genotyping+ancestry below $100, a value it had stabilized at for a few years. Family Tree DNA has a father’s day sale for $69 right now. Ancestry looks to be $79. The Israel company MyHeritage is also pushing a $69 sale price (the CSO there is advertising that he’s hiring human geneticists, just so you know). It seems very likely that a $50 price point is within site in the next few years as SNP-chip costs become trivial and all the expenses are on the data storage/processing and visualization costs. I think psychologically for many people paying $50 is not cheap, but it is definitely not expensive. $100 feels expensive.

Ultimately I do wonder if I was a bit too optimistic that 50% of the US population will be sequenced at 30x by 2025. But the dynamic is quite likely to change rapidly because of a technological shift as the sector goes through a productivity uptick. We’re talking about exponential growth, which humans have weak intuition about….

Addendum: Go into the archives of Genomes Unzipped and reach the older posts. Those guys knew where we were heading…and we’re pretty much there.

November 7, 2013

The future always advances

Filed under: DTC personal genomics,Personal genomics — Razib Khan @ 12:56 am

The last week has seen a lot of chatter about the slapping down of the diagnostic patent by Sequenom, Judge Invalidates Patent for a Down Syndrome Test:

A federal judge has invalidated the central patent underlying a noninvasive method of detecting Down syndrome in fetuses without the risk of inducing a miscarriage.

The ruling is a blow to Sequenom, a California company that introduced the first such noninvasive test in 2011 and has been trying to lock out competitors in a fast-growing market by claiming they infringe on the patent.

Sequenom’s stock fell 23 percent on Thursday, to $1.92.

The judge, Susan Illston of the United States District Court in Northern California, issued a ruling on Wednesday that the patent was invalid because it covered a natural phenomenon — the presence of DNA from the fetus in the mother’s blood.

The existence of intellectual property is a utilitarian one. That is, these are institutions which are meant to further the cause of creativity and innovation. Is there going to be an abandonment in this domain of the push toward technological innovation? Coincidentally in the last week of October Sequenom put out a press release which heralded some advances in its panel:

…The MaterniT21 PLUS test will begin reporting additional findings for the presence of subchromosomal microdeletions and autosomal trisomies for chromosomes 16 and 22, in addition to the previously announced additional findings for sex chromosome aneuploidies involving an abnormal number of the X or Y chromosomes. These additional findings complement the MaterniT21 PLUS test core identification of trisomies for chromosome 21, chromosome 18 and chromosome 13. With this expansion, the MaterniT21 PLUS test is the first-of-its-kind noninvasive prenatal technology (NIPT) to provide these comprehensive results from a maternal blood draw.

Sequenom Laboratories will begin reporting on these select, clinically relevant microdeletions, including 22q11.2 deletion syndrome (DiGeorge), Cri-du-chat syndrome, Prader-Willi/Angelman syndrome, 1p36 deletion syndrome, as well as trisomies 16 and 22 the last week of October. Results from a method validation study….

It seems that the firm’s main path to profit and riches is going to be to innovate faster, gain market share, brand recognition, and economies of scale. This seems as if it is a greater good for the public than its rents extracted through intellectual property monopolies.

The post The future always advances appeared first on Gene Expression.

September 16, 2012

The ecstasy and agony of prenatal information

Filed under: DTC personal genomics,Personal genomics — Razib Khan @ 5:34 pm

Slate reposts a piece from New Scientist, Do You Really Want To Know Your Baby’s Genetics? It is arranged as a series of questions which might arise from the new information. For me my frustration with this sort of discussion is rooted in reviewing old articles about “test-tube babies” in major newspapers from the 1970s and early 1980s. Today in vitro fertilization is banal and commonplace, but many of the same concerns were voiced back then which you see cropping up now in regards to personal genomics. My issue is not concern as such, but its inchoate character. It is not uncommon for me to encounter people pursuing postgraduate work in science who express the opinion that “it’s scary,” the “it” being genetic information. When further queried the fear is generally layers upon layers of formless disquiet, some confusion about the specific details, as well as a default stance toward the “precautionary principle.”


With all due respect this isn’t rocket science. There’s no need to be overly general, the issues we’ll face are precise and specific, and often actually implicitly or explicitly enumerated in pieces such as the one above, which nevertheless manage to convey an air of murky ...

September 14, 2011

Poll on personal genomics

Filed under: DTC personal genomics,Genomes Unzipped,Personal genomics — Razib Khan @ 9:08 pm

Genomes Unzipped points me to a Nature survey on personal genomics for scientific researchers. With price points down to $200 or so many scientists have been at least genotyped. Though it varies by domain. Many molecular biologists seem intrigued by the novelty of personal genotyping services. In contrast, in a room of a dozen or so population geneticists and the like nearly half are liable to have already gone through some service.

All that being said, I haven’t heard from people who want to make their genotype public in a long, long, time. Has the steam run out of that project? You might hear from me again with a subtle twist on this in the near future.

June 7, 2011

Why genetic privacy could be doomed

Filed under: DTC personal genomics,Genetics,Genomics,Personal genomics — Razib Khan @ 12:34 am

I was having a discussion with some friends who have all expressed interest in being genotyped or have been about putting their information into the public domain. They were a pretty savvy lot (half of the six had been genotyped), but one expressed the common sense objection that “someone could find something in the future.” In other words, a really creepy stalker could keep running your data through Promethease. Imagine you’re a really strange person, and you have a bunch of gentoypes of people who you want to know about, and you design a program which scours the academic literature and constantly notifies you when the individuals in your database pop up with a large effect mutation. I have no idea why someone would do this. Perhaps you could be blackmailed by someone threatening to disclose to your employer than you had a 50% greater chance of a heart attack before the age of 60 than the general population? Whatever the details of the concern, they’re general, ranging from inchoate to eloquent.


But all this is moot in my opinion. I think in 10 years most people will probably have at least a genotype with the most informative ...

May 31, 2011

Ban them! (including ancestry analysis)

Direct-to-Consumer Genetic Tests Neither Accurate in Their Predictions nor Beneficial to Individuals, Study Suggests:

Direct-to-consumer (DTC) genetic tests give inaccurate predictions of disease risks and many European geneticists believe that some of them should be banned, the annual conference of the European Society of Human Genetics heard May 31….

Here’s the abstract for the talk which argued that DTC companies don’t give the best disease risk estimates:

Objective: Direct-to-consumer (DTC) companies predict risks of common complex diseases on the basis of genetic markers. Given the low number of markers involved and their small effect sizes, it is unclear whether high-risk groups can be identified. We investigated the risk distributions generated by two DTC companies for 8 diseases.

Methods: We simulated genotype data for 100,000 individuals based on published genotype frequencies. Predicted risks were obtained using the formulas and risk data provided by the companies.

Results: The table presents observed and trimmed ranges of predicted risks. The two companies used different formulas to calculate risks. One company predicted risks higher than 100% for 5 out of 8 diseases, which for AMD concerned 1 in 200 individuals. Observed ranges were smaller for the second company, except for Type 1 Diabetes. Predicted risks higher than 50% ...

May 20, 2011

Don’t buy AIBioTech Sports X Factor kit!

I’ve been pretty vocal about the impending specter of genetic paternalism in relation to personal genomics, which I believe to be futile in the long term, and likely to squelch innovation in the United States in the short term. Like any new product category there’s a lot of hype and confusion in the area of personal genomics, but I think it’s important that we allow some mistakes and misfires to occur. Innovation and creativity isn’t failure-free.

With that said, I also think it is incumbent upon the personal genomics community, if there is such a thing, to “police” the flow of information. I have seen references in the media to a new personal genomics kit, Sports X Factor, selling for $180, from AIBioTech. My initial intent was to ignore this, as there is real science and tech to be covered. This is just another case of a biotech firm trying to leverage public confusion and gullibility into revenue. But if I think such a thing, I should make my opinion known, shouldn’t I?


So here’s the bottom line: If you don’t want to waste $180, don’t purchase a Sports X Factor kit, it’s just not worth the ...

May 5, 2011

A survey on personal genomics for a Ph.D.

Filed under: Blog,DTC personal genomics,Personal genomics — Razib Khan @ 11:13 am

Like John Hawks I get a fair number of questions from students. Some of them seem legit and I try and answer them, but sometimes they’re asking detailed things which would take me too long and it falls out of my task stack. And alas on occasion they’re clearly straight up asking me to write their paper from what I can tell. But today I got an interesting email from a doctoral student in England who found me via twitter and my blog, and was wondering if I could fill in an online survey for her research. It took me all of 5 minutes, so if you want to help them out (I’m thinking this is a painless way to increase someone’s sample size):

To fill in the survey, please:

Click here if you have bought a genetic test. (If you have bought a test but haven’t recieved your results yet, please still follow this link and just ignore any questions you can’t answer).

Click here if you are thinking of buying a genetic test.

April 19, 2011

Incest, “the children,” and personal genomics

Filed under: DTC personal genomics,Genetics,Personal genomics — Razib Khan @ 11:16 am

Mischa Angrist and Brendan Maher point me to two interest personal genomics related stories. First, a follow up on inadvertent uncovering of incest story from last winter in GenomeWeb, Incidental Findings:

Recently, he and his colleagues encountered a case in which a married mother of three children with cognitive and developmental disabilities — the eldest of which she conceived in a previous union — opted to submit their genetic samples for screening. The researchers discovered a span of homozygosity that indicated the oldest child was the product of an incestuous conception between first-degree relatives. When they informed the mother of what they found, Beaudet says she vehemently denied such a relationship and demanded that the test be repeated. “The test was repeated and [the result] was the same,” he says. “And then she sort of broke down and said: ‘My husband will divorce me if he finds out about this.’ … There are just a lot of difficult things that come up.”

A few years ago professionals had discussions about whether they should even divulge this sort of information which might destabilize the family unit. In particular in relation to paternity. I think that’s a moot point, the horse ...

July 23, 2010

Personal genomics & the state

Filed under: 23andMe,DTC personal genomics,Genomics,Health,Personal genomics — Razib Khan @ 10:13 am

Dr. Daniel MacAthur & Dan Vorhaus offer their takes on the recent hearings in Congress on the direct-to-consumer genomics industry, A sad day for personal genomics & “From Gulf Oil to Snake Oil”: Congress Takes Aim at DTC Genetic Testing. I guess I lean toward light regulation. I don’t think that DTC personal genomics will result in systemic decrease in human happiness, and tight regulation will increase the costs of innovation and constrain access and reduce affordability. Though I guess that for some that’s a feature, not a bug.

My main point, which I think I got across on the Genomes Unzipped comments is that fraud, error and misrepresentation are rife across many health-related sectors in American society. The nutrition and diet industry are prime examples. Bad journalism on the health beat causes way more suffering than DTC genomics kits ever will, as people who are not intelligent make precipitous decisions based on the latest result which managed to slip through the p-value gauntlet and are sexy enough to be written up in USA Today. And, there are widespread distortions within our health care sector which really need to be addressed (I’m thinking in particular of frank talk about end of life palliative care). With that as the basis for judgement I don’t think that the fraud and misrepresentation one can find in DTC personal genomics is exceptionally worrisome or notable to warrant such attention or focus. This is an inefficient allocation of concern and regulatory resources, driven more by the industry’s puffed up claims and the apocalyptic projections of the skeptics.

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