Big Problems and Slow Solutions

TILTed Genetic Testing

Even if you are not living with an invisible illnesses (like MCS, ME, Fibromyalgia, etc) you have probably been hearing quite a bit about the use of genetic testing to personalize medical treatment. It’s largely being used to assess risks, with varying margins of inaccuracy, for certain diseases, especially cancers. Genetic testing, especially analyzing the MTHFR gene, has also become fairly popular for us in the EI (Environmental Illness) crowd, both as a potential tool for developing a treatment plan and for adding to the dialog on genetic patterns that might explain a chemical sensitivity mechanism. I’ve been tracking the tests for a while and finally had one of them done a few months ago under the suggestion and guidance of my nutritionist, who works closely with my primary care physician. The three of us, patient, physician and nutritionist, share a practical attitude that makes for good teamwork. We went into this testing with an understanding of the test’s limitations. I knew it would not tell me how I developed chemical sensitivities or how I could heal from them. I read books on the former and talk to you guys about the latter. I was hoping the results would give me insights into why this happened to me in particular, what I might do to avoid future problems, and how I might mitigate some general health issues.
Before I share results, let’s back up and take an overview of what these tests are looking at.

Background By and For the Layperson
Chromosomes carrying our genetic information are replicated during reproduction. It’s a lot of complicated information to copy exactly so mutations occur, producing different versions of the same gene, called alleles. These variations make each of us unique and keep the species changeable. Variations that help us survive become the predominant version and those that cause disease do not. There are even more variations that are neutral, determining hair color, etc, and for these we cannot distinguish between which is the original allele and which is the mutation. Moreover, a single variant gene will rarely affect functionality, as organs and systems depend on hundreds of genes for one process and compensation is one of the body’s strengths. We can identify these variations by looking at the single nucleotides – A, T, C, or G – in the genome (or other shared sequence) in a species. For example, two sequenced DNA fragments from different individuals, AAGCCTA and AAGCTTA, contain a difference in a single nucleotide. This is called a single nucleotide polymorphism or SNP and in this case there are two alleles : C and T.

Research and data collection in this field are producing huge amounts of genetic information, and researchers are looking for patterns that shed light on risk assessment. This is not the same as understanding causality! However, it is a fascinating start to a very complicated puzzle. Not all SNPs are understood well enough to analyze or attempt an interpretation on that analysis, but more and more are. Once an allele has enough data from people’s genetic analysis, researchers can calculate an allele frequency, which is how often the variation occurs in a particular population set. Hopefully, there might also be enough data to confidently state what role that allele plays in what system and what effects the variation will have on efficiency of function. Ideally, the data could suggest whether there is an increased or decreased risk for particular disease or condition developing associated with SNP variation. What information is known is publicly available in various searchable databases which include SNPedia, Center for Human and Clinical Genetics, and the National Center for Biotechnology Information.

Lastly, remember SNPs are normal and common mutations that occur during reproduction. If our genetic code were to change due to environmental pressures, as a species adaption, it would take many more generations to see that effect. However, immediate changes can be seen in how our genes function, and that is called epigenetics. The epigenome turns genes off or on (inhibition or expression) by physical need or condition, like how our hair turns grey when we are older. Environment can effect when genes are expressed by either direct damage, hormone mimickers, or heightened or prolonged stress. The incorrect expression of a gene can also then be inherited by the next generation. I find this particularly interesting to any patients with a functional illness like ours but there is very little hard data in the area and it’s a bit off topic. Oops, back to testing SNPs, variations in the genetic code itself.

Testing and Regulation
There are some laboratories that offer analysis of certain SNPs for patients under a physician’s care. You can only get these tests through a doctor’s office. Since these tests are controlled by the medical community, the results are allowed to contain various analyses, assuming that the results will be overseen by the ordering physician, helping to interpret and advise. Genova Diagnostics does six different genomic tests focusing on different risk susceptibility. There are also companies that cater to prenatal screening (Natera and Counsyl) which also require physician involvement. On the other end of the spectrum are direct to consumer (DTC) genetic testing which has become very popular.

With DTC testing, the customer orders and pays for a test kit, then mails in their sample for analysis by spitting in a tube or getting swabbed in the mouth. The company analyzes a small portion of the genetic profile (small because the full profile is huge; even the resulting data from the small portion still seems like a lot). Customers used to be able to get interpretation of the data in terms of risk assessment and some advice in terms of diet, supplementation, or lifestyle changes along with the results. But in November 2013 the FDA sent a letter to the biggest DTC company in the field 23andMe, essentially warning them that they couldn’t offer medical advice. Eventually, after some delay and resistance, 23andMe removed all medical interpretation from their results. Now costumers get ancestry interpretation and raw data. As a result, genetic testing interpretation sites have sprung up. That’s what a lot of people do now; have one company do the test and another interpret the data. That is unless you live in the UK, where the Research Ethics Committee has approved 23andme to do the full job (1). *Update – 23andMe has been given FDA permission to market a single test that analyzes a patient’s Bloom syndrome carrier status, their first test approved for medical purposes.

23andMe is dominating the field for DTC genetic testing at $99 for a kit. The other DTC tests really focus solely on ancestry analysis. For interpretation there is Genetic Genie, Promethease, or Interpretome. Genetic Genie and Interpretome are free, though Genetic Genie asks for a donation, and Promethease is $5. While all the sites provide cautionary advice and disclaimers, I personally like Promethease’s agreement page such that the user has to actually read the document before using the site. The Genetic Genie and Promethease sites also provide examples of a test analysis, allowing the user to choose which site provides the format they are most comfortable with.

The FDA claims they only have an opinion on genetic testing insofar as it might be considered a diagnosis, treatment or prevention of a medical issue; the bureaucrats have no control over how or why genetic data may be compiled. I don’t mind when the government steps back on regulation (though not with the chemical or pharmaceutical industry – step up regulation there please!) as long as we the people then get the information to make informed choices ourselves. So let me share some thoughts from people who have researched direct to consumer genetic testing more than I have.

What “They” are Saying
New York Magazine, “The Google of Spit”, Apr 2014.
Database science does not work on individuals.
“Most diseases are activated not by one gene but by many, and though sometimes scientists know which genes correlate with disease, they have not established causality: how genes trigger the disease and under what circumstances.” The author also stresses the goals of the groups involved. 23andMe is after the big database to find patterns. The FDA is making sure individuals are treating their individual problems.(2)

Nature, “Regulation: The FDA is overcautious on consumer genomics”, Jan 2014.
This technology has not been around long enough for standards to be meaningful but the benefits of consumer driven health care currently outweigh the author’s concerns.
“Although the accuracy of the technology used is considered to be high, there are no agreed standards to which the company can conform for validating hundreds of simultaneous variant calls. There is also controversy about how to evaluate the accuracy of risks estimated using multiple variants or across ethnicities. And consumers might not read or fully understand the company’s clear statements that its tests identify only the most common genetic variants and cannot substitute for genetic testing ordered by physicians to assess specific indications, such as a family history of cancer.” But also, “Such consumer products could democratize health care by enabling individuals to make choices that maximize their own health. They follow the historical trend of patient empowerment that brought informed-consent laws, access to medical records and now direct access to electronic personal health data.”(3)

Scientific American, “23andMe Is Terrifying, but Not for the Reasons the FDA Thinks”, Nov 2013.
Know your testing source’s intention.
One of the founders of 23andMe, Anne Wojcicki, was married to Sergei Brin, the founder of Google and as the company has repeatedly stated, “The long game here is not to make money selling kits, although the kits are essential to get the base level data,” Patrick Chung, a 23andMe board member, told FastCompany last month. “Once you have the data, [the company] does actually become the Google of personalized health care.” The article states, “Although 23andMe admits that it will share aggregate information about users genomes to third parties, it adamantly insists that it will not sell your personal genetic information without your explicit consent. We’ve heard that one before. Back when Google was first launched, the founders insisted that the company would never sell you out to advertisers…While the FDA concentrates on the question of whether 23andMe’s kit is a safe and effective medical device, it is failing to address the real issue: what 23andMe should be allowed to do with the data it collects. For 23andMe’s Personal Genome Service is much more than a medical device; it is a one-way portal into a world where corporations have access to the innermost contents of your cells and where insurers and pharmaceutical firms and marketers might know more about your body than you know yourself”.(4)

Forbes, “Surprise! With $60 Million Genentech Deal, 23andMe Has A Business Plan”, Jan 6 2015.
Genentec, a pharmaceutical company, is paying big money for a long term deal with 23andMe. Its big focus will be on developing the database to assist in Parkinsons research.(5)

MIT Technology Review, “How a Wiki Is Keeping Direct-to-Consumer Genetics Alive”, Oct 2014.
It feels like civil disobedience.
“In barring 23andMe’s health reports, the FDA also cited the danger that erroneous interpretations of gene data could lead someone to seek out unnecessary surgery or take a drug overdose. Critics of the decision said it had more to do with questions about whether consumers should have the right to get genetic facts without going through a doctor.”(6)

What I am thinking
The science and technology is rapidly changing and the regulations are, as usual, lagging behind. All of this information is still data, not really knowledge, much less wisdom. The risk assessment associated with any SNP needs to be considered in a broader context. To do that, DTC consumers of genetic testing need to make sure they are fully informed on the allele frequency. The more you look at those numbers the more you realize how varied we all are; the word “normal” means very little! Secondly, any analysis that links variations to poor efficiency, illness, or disease is just that – a connection, not causality. Health problems develop from a pattern of susceptibility from genetic variations combined with exposures accrued through years of different life choices. And of course, the constant exposure to low level chemicals in our daily life that we have no choice about anymore. Oops, once again, I am off topic.

If you are struggling with a chronic illness or condition, especially those of an invisible nature, that drives its sufferers to search longer and harder for answers than patients with well understood illnesses, understand this before you go into genetic testing. The results will not tell you how this happened or how you can heal. They might help answer why it happened to you and how you can avoid future complications.

My Results
We did the Genova Detoxigenomics test. This test just focuses on the detoxification pathways and which ones might not work as efficiently as the average person’s. The results have helped me in some concrete ways. I never spent much time or energy on the “why me” question but now that I’ve seen the analysis, I really don’t. Having seen the pattern of my genetic variation “inefficiencies” just within the detoxification pathways, I now know I was a canary waiting to happen. As soon as I was born into a post WW II chemical laden society and furthermore decided on a career in a science lab, chemical injury was going to happen to me. I’ve also known that glutathione supplementation has been the cornerstone of what chemical tolerance I have built up but now I know I will always need to supplement it, dietary or synthetically, forever. I can’t make enough of that on my own no matter my levels of avoidance. I’ve learned that if I ever need a blood thinner, I need to throw some keywords at the medical practitioner at hand and have my primary physician talk to them until they reach an agreement on safe dosage. Because I can’t metabolize Coumadin as efficiently as the standard population on which the dosages are based. I’ve known that estrogen metabolism is also a problem for me, long before the testing, having lived through decades of menstrual cycles. But now that we know the extant of that problem we will adapt our approach from one of dietary sulfur boosts to a broader based approach that includes some supplements. And as a bit of comic relief, that one bad college trip from smoking marijuana was not an anomaly, any THC will mess with me horribly since I can’t really metabolize that either. Yes, I am telling my kids this as warning.

So as you can see, it’s not rocking my world but it is fine tuning some things. There are other SNPs to test that could shed light on the immune system or more on methylation and I might get to them soon. But a better use of my lab budget would be to test my ten year old daughter who already shows too much genetic similarity to me for comfort. I’ve blogged about this before, but to summarize, we have dealt her a very tricky hand of genetic cards. I will go to some lengths to gain information that will help her play those cards well.

Searchable SNP databases:
National Center for Biotechnology Information
Center for Human and Clinical Genetics
SNPedia

Physician ordered testing:
Genova Diagnostics
Counsyl
Natera

Direct to consumer (DTC) testing and analysis:
23andMe
Genetic Genie
Promethease
Interpretome

Articles quoted in the post:
(1)http://www.wired.co.uk/news/archive/2014-12/02/23andme-uk-approval
(2)http://nymag.com/news/features/23andme-2014-4/
(3)http://www.nature.com/news/regulation-the-fda-is-overcautious-on-consumer-genomics-1.14527
(4)http://www.scientificamerican.com/article/23andme-is-terrifying-but-not-for-reasons-fda/
(5)http://www.forbes.com/sites/matthewherper/2015/01/06/surprise-with-60-million-genentech-deal-23andme-has-a-business-plan/
(6)http://www.technologyreview.com/featuredstory/531461/how-a-wiki-is-keeping-direct-to-consumer-genetics-alive/

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5 thoughts on “TILTed Genetic Testing

  1. That is so interesting- I am of proud of you for doing it. We are on the fence at my house, but this information is so helpful.

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