Dancing Genes

I was prowling through the 23andMe site while I’m waiting for results, and noticed that the results will include a whole bunch of information in an area that isn’t my top priority, but which is interesting nonetheless.

23andMe: Ancestry: https://www.23andme.com/ancestry/

Dancing Matt takes a Journey with 23andMe

A friend of mine has gotten this test. Her whole family did, which turns out to really help a lot in deciphering results and figuring out what’s what. They’ve been kind of perplexed because they also hit the wall of “well, genomics just doesn’t know that much yet.” Their family was told they have genetics from a certain tribe of Indians in South America, when they know from their family history that they belong to a different tribe in a nearby area. When asked, the genetic scan company told them, “Well, we don’t have any genetic data from that tribe, and this is as close as we can get.” My friend’s family was offended that the report explicitly mentioned one tribe in particular without substantial supporting evidence. They wanted the gray areas to be overtly noted as gray areas. In some ways, it seems like the genetic reports, by pretending to be more clear than they really can be, are building up a reputation for hype. Hmmm.

Take Two

PGEN, Take 2

Well, I just did it. Sent off the sample for the 23andMe test. While I was waiting, I also finishing contacting all my immediate family members to find out if they had problems with my blogging all of this. I come from an exceptionally intelligent and educated family. They were all in favor of my doing this. I also emailed copies of the Pathway Genomics report to all interested family members (about half). They’re intrigued. Now, it’s waiting to see what the other report shows. I’m feeling impatient.

Curiouser and Curioser (What We Don’t Know. Yet.)

Curiouser & Curiouser

Wow. Moving along here.

Asked the genetic counselor why the celiac results weren’t included. Turns out that when I took the survey and it said that celiac results would be added to the test, well, the system didn’t check to see which branch of the study I was assigned to. I was assigned to Pathway Genomics, and they don’t HAVE a celiac test in their scan. Oh. They recommended I check out 23andMe. Oh.

That costs a chunk of change. A sizable chunk of change. And I’m in the middle of a small home renovation as a sequel to storm damage. Oh. I have to think about this.

Meanwhile some very interesting conversations happening and questions being raised in the PGEN thread in Patients Like Me forums. And while no one else on Twitter aside from me seems to be using the #pgen hashtag, there are also PGEN conversations happening there. As a direct results of chatting about the PGEN study with another study participant and an interested doctor, we’ve started swapping our data around via email. I mean, we are sharing our genomic scan results. The other patient/participant is in the 23andme branch of the study, but had previously gotten the Pathway Genomics scan, so I got to see how the report has evolved over time for that as well as being given permission to log in and browse around in her results on 23andme. Turns out several of my friends who are NOT in the study have also had these tests run, and those are resulting in more interesting conversations.

This has been fascinating! I’m not going to go into details in this post, but I’ve been very intrigued by not only what information is included but also how it is communicated. Both groups have room for improvement, and there are advantages and disadvantages of each. That will have to be another post.

One of the interesting parts of conversations with other study participants has been picking up things they know that I don’t. Or at least I haven’t heard. One tidbit mentioned was that the MTHFR mutation makes it hard to detox. I did a little searching on this, and the belief is that MTHFR deficiency impairs the body’s ability to process heavy metals. While most of what you find on the Internet about this is from less reputable sites, there are some actual research articles. Not a lot, though.

Pubmed: MTHFR (detoxification OR “heavy metals”): http://www.ncbi.nlm.nih.gov/pubmed?term=mthfr%20(detoxification%20OR%20%22heavy%20metals%22)%20

I was less concerned with that than I was with all the test results for conditions that run in my family for which the genetic scan says I’m at low risk. Let me try saying this a different way. There are all these conditions that run in my family. Lots. But the scan says I’m not likely to get any of them. Hunh? That sounded pretty unlikely. Unless I’m adopted or the test samples were mixed up, something like that. Frankly, I’m the spitting image of my dad and have heard tons of stories about my mom in labor with me. I really don’t think I’m adopted. I think the test has missed something important.

There were several of these results, including conditions that many family members have as well as conditions I already have. I’m a bit worried that if the genetic scan is shared with my doctors and says I’m at low risk for something where I know I have a strong family history, would the doctors perhaps relax and not be vigilant about testing for those conditions?

An added complication was that almost all of the conditions that run in my family that the test says I probably won’t get are diseases that are known to be common in people with celiac. That’s … interesting. The genetic counselor kept saying things like, “Maybe there are other genes for these conditions that we don’t know about yet.” So. Alright. Thinking through this.

Disease X is common in a family.
Disease X has proven genetic component & known genes.
Disease X is associated with a 2nd condition, Disease Y.
Disease Y also has proven genetic component & known genes.

If the genetic test is negative for Disease X, is the person also negative for Disease Y?
If the genetic test is negative for Disease Y, is the person also negative for Disease X?
Does Disease X in some fashion contribute to or cause Disease Y?
Does Disease Y in some fashion contribute to or cause Disease X?
Are Disease X and Disease Y linked in some way, or are they independent of each other, and simply cause similar symptoms?

That’s not all, it gets … complicated. And we don’t know enough, not remotely. So getting the genomic scan has, for me, created many many MANY more questions than answers.

I suspect that the conditions in my family for which I tested negative on the genetic scan actually do have a genetic component that wasn’t included in that test. I strongly suspect, given that they are mostly associated with celiac and celiac was not included in the test, that celiac is the root cause of all of those. Of course, there is no proof, and even if we do the next test, we still won’t know enough. But. But.

There are things in the genetic scan I want to share with my docs. But without the information about celiac, I don’t feel safe sharing the results with my docs. Especially since my wonderful doc who I trust is leaving and I’m trying to find a new doc. Knowing the answer to the celiac question might help fill in some important pieces. If that is negative, it might just make for even more questions and confusion. I kept coming back to how much money it costs. I kept thinking about waiting until I have more money, waiting to see how much money is left after the house is fixed. House vs health. House vs health.

Well, I did it. I went ahead and ordered the 23andMe test. Lord, I hope this is worth it.

I Can Do WHAT With Coffee??

Running around like a chicken

I remember the first time I tried coffee. It was Folger’s instant. It was like an instant WOW KAPOW KAZAM KABLOOIE. Not knowing any better, I had half a jar over the course of a day. (It was a teeny tiny convenience store jar, maybe 2 ounces?). When I went to work that night, I was gleefully buzzing around working like a little speed demon. My boss, a tiny quirky blonde woman, gave me a strange look, tilted her head to one side, and told me I had a great future ahead of me as a drug addict. I had no idea what she was talking about. I remember just as vividly the next morning when I woke up. I remember dreaming that I was dead, and waking up thinking I was. That only lasted a brief moment, but it was a decidedly memorable and uncomfortable experience. I’ve been wary of coffee ever since.

So much has happened with this project over the past week that I can’t keep up with the blogging I want to do. I have several more posts lined up in my mind waiting for time to write them. This one comes from the next piece in the report, the Drug Report, in which they scan the genome for unusual reactions to ten (10) medications. Today I’m just looking at one. You can guess, of course, from the picture and title.

COFFEE / CAFFEINE!

According to their test scan I am a fast metabolizer of caffeine. “Aye, aye, aye! Andale, andale! Arriba, arriba!” to channel the ghost of Speedy Gonzalez. The medical importance of this is that I am relatively unlikely to suffer from a heart attack as a result of ingesting too much coffee. Or am I?

In real life, I do have some heart arrhythmias, and coffee makes them, well, it makes my heart behave badly and makes me feel quite unwell. Also, I can’t tolerate it. Because of the way coffee messes with my blood sugars, I gave it up almost ten years ago, and switched to decaf, black, no sugar. I’ve since learned that coffee was a big contributor to my problems sleeping. (DUH!) If I even have one cup of DECAF after mid afternoon, it keeps me from going to sleep at night, I’ll just toss and turn. So I avoid it. Decaf only, never after lunch.

I made a phonecall to the genetic counselor on staff at Pathway Genomics and asked her about this. Saying that I was relatively safe from the ill effects of caffeine seemed … like perhaps they had someone else’s sample. She almost laughed. Evidently they get this question a LOT. Fast metabolizers of caffeine tend get a strong hard buzz FAST. They react fast, they almost over-react. They really feel it.

Oh. Right. That makes sense. OK. But … so why do such tiny amounts of decaf coffee keep me up at night? Well, there she was stumped. Good question. About all she could come up with was that there must be something else going on. So maybe there is something else in the coffee besides caffeine that is keeping me awake. Or maybe there is some other gene that is effecting how my body interprets caffeine. So many things that happen with us are not the result of a single gene. And we just don’t know everything about the human genome.

“Here Is A Human Being,” Redux

I’ve talked here before about why I’m participating in the study, a couple of times! What I haven’t talked about is the book that got me thinking about it at all.

Here Is A Human Being, by Mischa Angrist

Of course, working in healthcare, I had heard about personal genomics. It was on my horizon, something about which I wanted to know more. When I was offered a review copy of the new edition of Here Is A Human Being, At the Dawn of Personal Genomics by Misha Angrist, I thought that would be a great way for me to accomplish that goal.

For context, I’ve written a few book reviews in my past. Enough so, that I have my usual strategy: read the intro and conclusion closely; give attention to the Table of Contents and the index; flip through and do spot checks for chapters or sections or illustrations that particularly attract my attention, read those; extrapolate to the rest of the book. Please note, that for a solicited book review, I rarely actually read the entire book, instead reading enough to get a sense of the overall work. This was different.

Ruth, who sent me my copy, kept gently nagging me to actually write the review. I kept pleading for more time because I wasn’t done yet. I wasn’t making it through more than a page or two at a time. I kept stopping to look things up. Checking the footnotes or citations. These were often incomplete (which, as a librarian, frustrated me NO END!), so I’d break out my phone and look it up myself. Pop the link out to Twitter or send it to myself to bookmark. Prowl a couple related links while I’m there. Then go back to the book. Someone’s mentioned. A name or a company I don’t know yet. Repeat.

This is a slow process. Rewarding, engaging, intriguing, demanding, but not remotely speedy. As you can see from the photo, I’ve been carrying this book around for quite a while now. The actual object of the book is ornamented with papers sticking out of it, embroidered inside with scribbles and underlines and comments and questions, highlighted with wear and grime along the edges from having been a close companion over a period of time. I didn’t just read the book, I immersed myself in it.

For those who don’t want to read the actual “review” part of this, I’m going to interject here the main takeaways that influenced me. As I read this book, there was certain themes that slowly took shape. In the book, Misha switches between telling his part of the story, and conversations or events that involved the key players. In these candid conversations, the leaders in the personal genomics field kept talking about their own reasons why they believe this is important, what they hope will come from personal genomics, the potential impact, the benefits, the barriers. They worry. There are concerns about what happens if people DON’T participate? What if people’s concerns over personal privacy win out over the sharing of data necessary for leaping into a new realm of research and discovery?

They’re talking about a powerful shift in the model of how science is done. And it depends on us. The book doesn’t pound on the issue, but in different ways, different words, different places, different people kept expressing similar concerns. The idea sank in. I found myself concerned about the same ideas. I started hearing and seeing the same concerns expressed in other areas. Gradually, over a period of months, it became clear to me that this — big data, sharing data, personal transparency — are all critical to this paradigm shift in science as well as general knowledge, critical to moving us forward, beyond the status quo into the next level of understanding and learning. And if we don’t, we don’t go forward, but backwards. This is when and why I started to feel driven to get involved, somehow.

Now, about the book. Here is a Human Being really needs to be read like a story, and it also calls out to be read like deconstructing a piece of jewelry or craftwork prior to replicating the design in a new media. It has both a natural flow, and a sense of profoundly subtle (almost invisible) craft and design.

There is no conceptual organizer given at the beginning of the book, like the Dramatis personae or a timeline. There is no cognitive structure to help me understand this is where I began, this is how the book is evolving, and this is the expected path for getting there. My masters research focused on applying an educational technique that was then called an “advance organizer.” The oversimplified rule of thumb was tell them what you’re going to say, say it, and then tell them what you told them. Me, I like to include something about WHY, why it’s important, why it’s valuable information to you, what are *you* going to get out if it. In this case, he might also want something on what the value was to him.

Through reading this, I’ve ended up reading the personal stories provided on a number of the personal genomic corporate websites, but I just can’t trust them. They read a bit fake, like the marketing pieces they are. Misha doesn’t. Misha sounds honest and real. He says, I had these questions, I had these doubts, I had these concerns. I did it anyway. This is why. This is what I found, what I learned, how I learned it.

The book has important, excellent, well-crafted content. It tells a critical story. It tells a complex story. I agree that you don’t need to be a scientist to understand it. However, it doesn’t always include the context to make it easily accessible or an easy read. The story parts read easily, but without the cognitive construct into which to fit the pieces, I am having to create that myself as I go along. I am kind of mentally outlining the book as we go. Just when I think I know where he’s headed, and I settle in to just focus on reading, he changes direction. I react, “Whoa, that isn’t what I expected, what’s going on now?” and I start again digging into footnotes and background research.

My approach to reading this book might have been a mistake. It certainly took long enough! It might be easier to see the most important part of the book, the story. The story only gets more intense and engaging as the book progresses. And it has a worthy ending.

What the Heck is MTHFR Deficiency?

Mother and Baby

The first item on my report was … that I am a carrier for a genetic condition. Whoa! Really? The next question was, “What the heck is MTHFR Deficiency?”

I dug around a bit online and found out this is, shall we say, not a bit deal. One of my first steps is usually to try to find out other names for whatever it is I want to know. Another name for this is Methylenetetrahydrofolate Reductase Deficiency. Ie. Methylene-Tetra-Hydro-Folate Reductase Deficiency. It is also associated with Homocystinuria, and some people call them the same thing (but that seems to not quite accurate). The short version is this is really common, and even if you have it usually it isn’t very serious. Chances are you could have it and never know it.

They say 45% of white Americans will have at least one copy of the various genes that are associated with this. I have two copies, but of two different versions. That probably means that both my parents had one, but might not. I don’t know enough yet to make sure, and would have to get more information. I don’t know enough to understand if the two versions are on the same gene (a copy from each parent) or if they are involving multiple genes with related effects. If both my parents have it, then my other siblings probably all have at least one copy, which wouldn’t be a big deal if it was true. When it is most important to know about this is when you are having kids, and all my sibs have had all the kids they are going to. The public info about this points out that the main solution is to take vitamins with folic acid in them while pregnant, and since they recommend that for everyone anyway, you’re covered as long as you follow standard medical advice.

Here is the link, out of all the ones I looked at, which had the most helpful information for me.

Counsyl: MTHFR Deficiency: https://www.counsyl.com/diseases/mthfr-deficiency/

What was interesting for me was when I started looking at the Homocysteinemia aspect of it.

Pubmed Health: Homocystinuria: Cystathionine beta synthase deficiency: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002179/#adam_001199.disease.symptoms

I fit bits and pieces of the description. Obviously, I’m not intellectually disabled, but I do have:
– High arches of the feet
– Knock knees
– Long limbs
– Nearsightedness

These all could be attributed to other causes as well, but I found it curious. I have particularly strange feet (at least according to shoe salesmen), and limbs so long that none of the normal ergonomic guidelines apply to me. I am also mentally noting that they say to be particularly careful of blood clots for people with this condition. As far as we know, I don’t have the condition, but this is something I’ll want to share with my doc and discuss. I’ll also want to talk about this with my kids and siblings, even though it is not a reason to worry.

Well, That’s Disappointing

Zera: Environmental Indicators: Face with Tears (Detail)

I’m hoping that I misunderstood something, and that more info is coming later. I received the results — 91 page report! Going to take a little time to dig through it. My immediate response was, there are some real issues with their graphic design, hmmm. They do this clever color-based top-level design for quick scan of the results, but I suspect it isn’t truly visible for persons with color-blindness, and they don’t provide the supporting design for those persons. Rule one of design for persons with color blindness is don’t depend solely on the color to carry the message, combine the color with words or numbers.

Next response was, but … but … but … where’s the results for celiac? When I filled in the survey it said they would include that, but if they did, it isn’t in these results. That was my primary motivator for doing this, and if I don’t get that info, I am suddenly seriously unmotivated. Not that I won’t look at the other parts, but my heart isn’t really in it.

More later, as I explore. There doesn’t seem to be as much information as I’d hoped.