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I am also very appreciative of you sharing this. It is so much harder to pin the issue on the vaccine when there is a couple of months between the shot and the sudden onset. I take it that it was the first shot in early June, and then the 2nd shot 3 or so weeks later, and then the flare was late August. They typically don't follow issues after 6 weeks, which is a problem because then anything that happens after 6 weeks is immediately dismissed (which is very wrong, in my opinion). Have you considered reporting the event to the VAERS data base? Anyone can report. There is also a survey for P/P patients and reactions to the Covid-19 vaccine being run by the International Pans Registry (IPR). My guess is that she would have to sign up herself to do it. I don't know if there is anything in the survey criteria that would exclude your daughter, but it is very important (from a science point of view) for this kind of story to get included in such a study, and at VAERS (even though they will tend to discount on account of the timing).

The post of this thread was edited for an important revision. Also, my co-author Sam Keating and I recently completed another genetic study about P/P, that is unusual in that it is quite different than a typical genetic association study. The work is done, and with exciting results, but it is not yet formally or informally published - we need some more time for some additional checking. So we can't show results, but you can read what the study is about via its registration plan, here: https://osf.io/ck5un .

I just finished another study, checking whether the risk alleles of SNPS for elevated uric acid occur more commonly in PANDAS and PANS. It looks like the answer is no. The report I did is here: https://osf.io/35sx6/ This idea to check out uric acid genetics came from a P/P mom. I think it was a great idea, that is why I spent a lot of time getting that "no" answer. If anyone else has any good ideas, let me know! I am motivated to make use of this data.

Edited: A final phase of analysis of 23andMe and AncestryDNA data contributed by parents of kids with PANS or PANDAS initially found 5 SNPs statistically significant in these disorders, but only 2 replicated in additional work recently completed (and uploaded as a revision to the report): SNP _______ risk _ Odds Ratio rs10493812 __ A ___ 4.1 rs5029936 ___ A ___ 2.0 You can read and download the brief report at https://osf.io/53yve/. If you want to look up these SNPs, it would be good for you to read the 3 short paragraphs of Section 2 of the report. The spreadsheet with more details at https://osf.io/br2kh/ was not updated for the replication work; it lists the original 5 SNPs (that spreadsheet is best viewed in excel after downloading).

If anyone is interested in participating in this project by contributing data, I will be taking extra data until the end of this month (Jan/20). This time, I will be taking AncestryDNA data too. I have decided to go ahead with a 3rd (and final) phase of this genetic association study, where I check all the SNPs called in 23andMe and AncestryDNA, not just a small, predetermined list. Well, not quite all, because some aren't reported on in databases, or don't have an rsID, but it is huge chunk of work. For those interested in technical details, the plan for this study can be found here: https://osf.io/q4y2k/registrations.

We did find one other statistically significant SNP when combining data from the previous pilot study and this replication study: rs1042098. The tallies for both significant SNPs are: AA AG GG rs1042098 66 28 5 (there were 99 calls) expected# 42 45 12 TT CT CC rs2811178 23 21 10 (there were 54 calls) expected# 8 25 21 Although there are 138 participants (pilot + replication studies combined), not all versions of 23andMe and AncestryDNA called both SNPs above. For example, neither of the two SNPs above are called in 23andMe v5, nor most AncestryDNA data sets.

I have received the 70th data set (the goal for this replication study), and of course I couldn't resist checking the results. I was very surprised to find that the main SNP we were trying to replicate (the one related to MS that was unusually common in the pilot study) was not in fact unusual among this newest 70 PANDAS/PANS patients. I will be doing some checks around this, but it should be concluded that that SNP is not associated with PANS or PANDAS. But another SNP, rs2811178 (on the DPYD gene, 97981242T>C) has been shown in this study to have met criteria for statistical significance. That SNP's T allele (which normally has a frequency of about 38% among the mostly European population of the participants) is more common allele than the main allele in the P/P population for which we have data. It is not an "if and only if" genetic variation. Most certainly not everyone with a T allele has PANS or PANDAS (because a lot of the general population has at least 1 T), and there are also plenty with P/P (18% among our data) that do not have a T at all for rs2811178. It is just a risk factor for P/P, that'ss all. The above is a good find, but overall, the result from this study is disappointing for me. Besides a replication, I was hoping for more than just one out of the other 9 we were testing for this study to turn out to be significant. One or 2 of these might have been significant with more data (because they were still a little bit unusual), but I won't be trying to get more data to show that, or to do a replication of this rs2811178 finding. This poor result forces me back to the drawing board, though. I am considering checking the data I have now amassed between the pilot study and this one, for all SNPs called by 23andme. Besides being a tremendous amount of work, there is a significant "penalty" in the analysis for checking so many SNPs, that makes proving significance quite a bit harder, so I will think more about this before embarking on it.

It has been a long road, but I am in the "home stretch" of data collection for this study: I need only 10 more participants to reach the goal of 70 data sets. So, this is an appeal to any of you that have 23andMe data for your PANS or PANDAS child, to consider participating. Also, I am taking the opportunity to link to a good podcast on what has been called the "replication crisis". This genetic study I am doing is partly a replication of an initial result in a pilot study. Successful replication is very important because up until recently, half or more of all peer-review, published studies didn't replicate (which implies, they are wrong in their conclusions). Here is a link to a written transcript of the podcast: https://www.cbc.ca/radio/ideas/psychologists-confront-impossible-finding-triggering-a-revolution-in-the-field-1.5344467 and here is the actual podcast itself if anyone interested prefers listening: http://21393.mc.tritondigital.com/CBC_IDEAS_P/media-session/1cd5524d-881b-45af-b51a-0957b6046af8/ideas-vUWHypta-20191101.mp3 (right click and "save as" to download)

More Q&A from elsewhere: Some of you have looked at or downloaded the report for the previous pilot study at https://osf.io/pf7q2/ (there have been 174 downloads to date). Recently, I did an important update to that report. It was unfortunately a disappointing update to do, because it was to include statements (and corresponding analysis) about a Turkish genetic association study (the one presented at the Common Threads conference last year) that didn't replicate amongst our kids. It could be the case that genetics among Turkish P/P kids are not the same as among the mostly European kids of our study, so this doesn't mean that one or the other study is wrong. But even that scenario is disappointing, if P/P genetics is that complex. This lack of replication also does not mean that mannose-binding lectin (the gene implicated in that Turkish study) is not important among our P/P kids - there are very very many other SNPs in the MBL2 gene; this was just one. Q: please forgive me ... but can you clarify your comments in more simplified terms? A: Sure, and I can go just a little further, too. Someone else (in Turkey) says that there is a genetic variation they showed was related to PANDAS. Anyone with genetic data from lots of P/P kids can check that. We have some (collected back in January), but it doesn't show that genetic variation to be associated with PANS and PANDAS. This doesn't mean their study is wrong, or ours is wrong. It could be that the genetic variation they found was associated with PANDAS in Turkish kids, but not the (mostly) European kids we had in our data. This is disappointing. But we still do also have a result from our pilot study, that we are trying to show is true with a 2nd independent batch of data - that is one of the goals of this post requesting participation. It is a good idea to check a result by replicating (doing it again).

It has been a while since I used it, and I don't fully remember. I don't recall struggling, though. I also used Promethease, and that was more difficult, but with much more results. I recently had recommended to me SelfDecode (www.selfdecode.com), but I haven't used it.

Oh - I did use my credit card, so they have my name - but it wasn't my data. So, I need to admit that I was not completely hidden from them. it would have been slightly smarter to use my wife's (she kept her different last name), but that wouldn't have been totally bullet-proof either. I wonder if a paypal account can be temporarily setup. I think not answering health questions is important. I used a fake name for genetic genie, and it was free.

Another paraphrased Q&A from one of the 10 or so FB groups this is also posted in: Q: I'm happy there is research being done but ppl need to be careful where u r sending your child's identity and genetics! ... This doesn't sound safe and not sure results would be publishable. A: The publishing is less formal, in a different arena than most researchers publish, which is at Open Science Framework. If you don’t know me, you can always upload anonymously. ... If data is completely anonymous (the first thing I do is anonymize it anyway), I can’t fathom any danger. I personally don’t trust the corporations. When I got my sons 23 and me data, I put in a fake name, and didn’t answer any health questions. That’s not exactly per their policy, but that way some insurance company (or anyone) in the future can never know my sons data. I have similar misgivings about the various websites that let you upload data, like genetic genie and nutrahacker. What do they do with your data, and your name, and health questions that you might answer? Doing it anonymously for people and organizations that you don’t know and trust -that is the ultimate protection if you are concerned.

For those that may not have 23andMe raw data on their own computer, here are some instructions for re-downloading from 23andMe: 1. Sign into your account at www.23andMe.com (the sign-in button is near the top right). 2. On the right hand side click on the arrow beside your name and scroll down to "browse raw data" 3. Click on "browse raw data" and on the page that opens just under 'Your Raw Data' there is a note "You can view or download your data at anytime". Click on the word download which is highlighted in blue. At the bottom of the page that appears (read, and scroll down), click the "I understand" box, and then the blue 'Submit Request' button. 4. Once 23andMe have retrieved your data, you will receive an email that the data is ready to be downloaded. It might be a while. 5. Following the instructions in that email, you can then save the downloaded data to your computer - remember where you save it to. 7. Then return here, and click on one of the links at the bottom of the starting post to this thread. 8. That link takes you to Dropbox, which requests your data (pick the left button), and you can then browse to your downloaded data file on your computer to select it.

Q: So are you looking at genetic vulnerability? What are the long term goals of your study and how might it affect kids with these conditions in the future? A: Yes. The “holy grail” of a genetic study would be an “if and only if” genetic variation as has been found for Cystic Fibrosis (CF), where if you have the genetic variation you have the disease, and if you don’t have the defective gene, you don't have the disease. But autoimmune diseases don’t seem to be like that. Instead, dozens or hundreds or maybe even more than a thousand genetic variations seem to increase or decrease the odds of getting the disease/disorder/syndrome. Nobody (that I know of) has established any genetic variations associated with PANS, and for PANDAS, there have been (as far as I can find) 3 published studies (all from Turkey), that haven’t yet been replicated. Two of them didn’t replicate in our pilot study (that doesn’t prove either study is wrong; different ethnicities could have some different causal variants), and on the other I have concerns on the way the stats were done. PANS and PANDAS is way behind other diseases and disorders in laying this genetic groundwork. Once the genetic groundwork is laid, and replicated, experts in biological pathways need to go at it, to figure out what each genetic variation’s role is, if any, to understand which processes in the human body are affected. Here is an example of some of this kind of biological pathway discussion: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654249/ . We don't have all processes and pathways in the human body mapped, so this step can't be timelined. I am not well informed around this part of the puzzle, but I can easily imagine it being years or decades before there are significant understandings established. Or, we might get lucky and stumble across something sooner rather than later. Then, the final phase would be treatment development, which could also be a long timeline. There is nothing innate about genetic studies that dictate what ultimate treatment could be. They don't have to beget pharmaceutical interventions, though our financial and academic structures do seem to be geared that way. But still, there is no reason a genetic understanding can't spawn a dietary or other non-pharmaceutical treatment solution. These details tend to make the long road feel overwhelming, and there is still so much more to the overall story. But as an example, the discovery of the CF gene (in 1989) has over the past 30 years greatly extended the life and comfort of those with the disease (http://www.sickkids.ca/AboutSickKids/Newsroom/Past-News/2014/25-years-later-the-impact-of-the-cystic-fibrosis-gene-discovery.html). With PANS and PANDAS, we need to get going. There is one other nearer-term possible benefit from this kind of study that I have stumbled across, an idea inspired by the very Turkish study whose math bothered me. It's the idea of a predictive model based on genetics: a long shot, and bound to be controversial (23andMe is "not to be used for diagnostic purposes"). This would ultimately require more data than I am getting here now, and likely more SNPs of significance than I can show in this study (which is 10, if luck is in the wind), in order to work even half-decently. But I have to at least poke at it.

Q: Can you use AncestryDNA raw data? A: We did use ancestry for the pilot study, but it doesn't call 7 of the 10 SNPs I am looking at this time around. Because I am going to stop when I get 70 data sets, getting Ancestry data sets will mean less data for those 7 SNPs, which means weaker results for them. So, we won't be taking AncestryDNA data sets this time.