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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.

Q: Will participants get to see the final results of the research? A: Most definitely! You can see most of the results from the original pilot study at a link quoted near the beginning of the post (which actually serves as a consent form). We are hiding the identity of the SNP of significance so that this replication study cannot be accused of collecting data from people that knew they had they risk allele for that SNP! ... you (and everyone else) will be able to see results at an Open Science Framework website. It will be somewhat similar to the results shown for the pilot study.What I will do for any participant that asks, is point out (by PM) which column of data represents you or your child, so that you don't have to look up those 10 SNPs we are looking at in your raw data.

More Q & A from elsewhere: Q: Can you use DNA date from another source ... or do you need the raw data? A: Because the frequencies of risk alleles can vary quite a bit by ethnicity, I use the full raw data to give an ethnicity report (at GEDmatch, where I load only de-identified data - this is mentioned in the post above that doubles as a "consent form"). I use the frequencies associated with 6 main ethnicities to effectively create a control group from dbSNP (a database of allele frequencies). So, sorry - I do use a good chunk of the raw data.

I am going to post here paraphrased questions and answers from other private places where this post was also placed. Q: I can't remember - Can you tell me if I participated in the original study? A: ... I can't tell you right now because I don't have a list of the names on my computer where the de-identified data is. I've never had a computer hack or theft or break-in at my house, but just in case any of that happens, I kept the list of names identifying which data belonged to whom written on an (unhackable) piece of paper locked in a completely different place, and I am not there right now. I will have the same security in place for this study, and will let you know if you participated later.

If you or your child have a PANS or PANDAS diagnosis from a licensed medical practitioner, and you have 23andMe genetic data for that person, you are invited to participate in a follow-up research study titled “Replication of a Genetic Association Among Patients with PANDAS or PANS”. This study is being conducted by Bob Horvath, Michaela Holden and Sam Keating. We are "citizen scientists” with some qualifications in statistics and data manipulation, and direct experience (ourselves or family members) with PANS and other autoimmune or immunological conditions, as well as autism. The purpose of this study is to replicate a specific variation in DNA that was found in a previous pilot study to occur more commonly among those with PANS or PANDAS (P/P) than the general population. You can see details of that pilot study here: https://osf.io/pf7q2/. In this replication study, we also hope to demonstrate statistical significance for up to 9 other genetic variations known as SNPs, and begin development of a predictive model of P/P based on genetics. We will post a link here to the results. Participation in this is entirely voluntary. You can choose to participate anonymously, or with your name attached to the data. There will be no effect on your relationship with the researchers, or any other negative consequences with not participating. If you agree to participate, you will be asked to click on a link below and upload 23andMe data for one person. You may also email your data (see below). Note that for this study we cannot use additional data of close relations, and, if you participated in the previous pilot study, we also will not be able to make use of that same data, or that of close relations of those that participated in the pilot study. The data will be collected regularly from the upload site, until a total of 70 valid data sets is reached. All data uploaded will be safely stored (with no direct identification of participants) on two computers only. Those received after the 70th data set will also be retained for possible later use. Even if you give your name, the data will be separated from and stripped of that name before being stored. After the initial upload and de-identification steps, no other person, website or online service will have access to your data with your identification attached to it. The de-identified data will be uploaded to GEDmatch in order to obtain ancestry, and to confirm no close relatedness to other participants. For those that contribute anonymously, the only link between the principle researcher (Bob Horvath) and you will be a fake name and email address that you give at the upload site. You are free to withdraw from this study at any time. However, once you submit your data, the only way to withdraw anonymous data is if you contact Bob Horvath and reveal your fake name, so that it can be known which data is to be removed. This step could reveal your identity, but your data will be removed from the study. Only Bob Horvath will have access to this full data. De-identified results of the SNPS of interest and analysis of the data will be made known at the Open Science Foundation website. There are no known risks associated with this study, beyond any risk there may be associated with the original data existing (e.g. on the originating site, such as 23andMe). While you will not likely experience any immediate direct benefits from participation, information collected in this study may benefit you and others in the future by helping to determine genetic factors associated with P/P. If you have any questions regarding the survey or this research project in general, please contact the principal investigator, Bob Horvath, at bobhorvath@alumni.uwaterloo.ca By clicking on one of the links below to the upload site, or sending data to the email address above, you are indicating your consent to participate in this study. If you want to contribute anonymously, submit only a fake name and email address at one of the links below. If you use a fake name, make it unique (unidentifiable by others) and make a record of it, in case there is any need to try to contact you (via a comment to this poll in the online groups it is listed in). To upload data for a person that has been diagnosed by a licensed medical practioner(s) with both PANS and PANDAS, click on this link: https://www.dropbox.com/request/0dQQliIe42uzZu28kiMU To upload data for a person that has been diagnosed by a licensed medical practioner with PANDAS (but not PANS), click on this link: https://www.dropbox.com/request/dP7F70p7JdZlWCickAaV To upload data for a person that has been diagnosed by a licensed medical practioner with PANS (but not PANDAS), click on this link: https://www.dropbox.com/request/TrZl51Gi9C2HDDUgx5B3

A report on the pilot study of this post has (finally) been uploaded at Open Science: https://osf.io/pf7q2 . The new files are the last one (the report), and the first one (the spreadsheet). I am wanting to replicate the finding, and am working towards that. There is no earth shattering new results there that weren't posted above. For example, the SNP that is statistically significant is still not revealed (because doing so could bias the replication study). The report is several pages of methodology details (the whole thing is 5 pages), so, I don’t recommend people read it unless they are really interested in the how of it all. It’s just that we said we would analyze and report, and so here it is.

Sorry I didn't notice your response until now. Well, we are wanting to replicate for good measure, but as a first approach, we are trying to partner with folks that have existing data sets. They don't know the SNP, and I don't see their data in advance, so I feel that blindness protects us from a certain kind of p-hacking criticism for already-collected data. If working with others falls down, I might consider doing the replication with data collected as we did in this first round. I would be happy to let you know if you wanted to contribute. As to your 2nd question, the simple bonferroni correction was applied for our finding. So, the target p for significance was 0.05/10,340/2 = 0.0000024 (the /2 was because we were checking both tails), and because we were well under that simple correction, we didn't do anything more sophisticated. But this target also left some possibilitiies that might be significant as undiscovered. I have understood bonferroni to be pretty close to the reality - do you know differently?

After checking 10,417 SNPs in the PANS genetics data sets that were donated for the above study (from this and other groups), we finally found one that does have a "statistically significant difference" in incidence between 68 PANS kids (who are mostly of European ethnicity), and a representative general population. This is not at all like Huntington's, where if you have the mutation, you've got the disease, and if you don't, you are clear, 100%. Rather, it is like what we know so far of many immune disorders, where there are many gene mutations (even hundreds of them) that are associated with higher incidence of a disease/disorder (i.e. slightly greater chance of having it with a mutation, but nothing guaranteed either way). For our SNP, almost half of PANS kids don't actually have the risk allele. But a much smaller fraction doesn't have it in the general population; that is the reason it was caught as statistically significant. So, the interesting thing about this mutation (a SNP allele) is that it has been linked to MS in another formal, published study. When we couldn't finding anything significant with all the "popular" SNPs that people were paying attention to (like MTHFR and FUT2), we eventually branched out to checking ones associated with diseases, particularly autoimmune diseases. We aren't going to announce the specific SNP just yet, because we are interested in corroborating it with a second set of data. We don't absolutely need that corroboration (because the result is clearly statistically signficant, p=0.00000015 for those that are familiar with p-values), but a replication would make the find so much stronger.

I committed to feed results back as they trickle in, so here is one such result: For MTHFR A1298C (rs1801131), there were 70 sets of data: - 5 were homo for the risk allele (i.e., +/+) - 23 were heterzygous (+/-) - 42 of them did not have the risk allele at all (-/-) For MTHFR C677T (rs1801133), there were 71 sets of data: - 5 were homo for the risk allele (i.e., +/+) - 26 were heterzygous (+/-) - 40 of them did not have the risk allele at all (-/-) The first result above is a lower count of risk allele than the general population, and the 2nd is a little higher - but neither statistically significantly so, according to how we setup this analysis. Particularly together, the two of them are pretty much like the general population in terms of number of the risk alleles. I hope this result is not upsetting for any that feel these MTHFR SNPs are a significant player in PANS. Because it doesn't correlate wtih PANS doesn't mean that it isn't something of significance for your particular child. So far, we have only tabulated results like the above (how individual SNPs for these PANS kids fare against the general population). We are still wanting to look at other patterns of many SNPs together among the participants, which might show something statistically significant even if an individual SNP doesn't. It can also be the case that for a given individual, a certain combination of SNPs, including these MTHFR ones, work in a way together to affect the disorder. It is really hard to do either of those kinds of analysis with our genetic data though, so we'll see how our investigations of that works out.

Note: This has been approved for posting by Forum administration. For any that contributed to this genetic study that we posted here (and elsewhere) - thank you so much! The cutoff was last night, and we had a great result - 71 sets of data. I will post some tidbits of "aggregate" results here (and in the other groups this was put in). I am wary of posting full results on facebook, because then facebook could claim some ownership. Instead, full analysis results (data in aggregate form only) will eventually be posted here: https://osf.io/pf7q2/?view_only=ba9efeabb38e4a22adced3b5ba4dc5a5 That link above is live to the public now, and you can see (in the last revision of a registration plan), what are the 78 SNPs that we have looked at. We are going to look at many more SNPs, though, and do lots more analysis than what is listed there. The plan was just to lay out in advance what we could declare as significant in this pilot study.

If anyone is still interested in participating, there is only one more week until the cutoff for this pilot study. I am not sure if anyone from this group has uploaded data (it would be some work for me to check where non-anonymous donors are from, and of course I won't know for anonymous donors), but there are 40 participants so far from other groups. It is exciting work for which there has not been (to the best of my knowledge) anything published to date. We intend to publish publicly only at Open Science Foundation, not (at least at this time) formally in any peer-reviewed journal.