Jump to content
ACN Latitudes Forums

bobh

Members
  • Content Count

    332
  • Joined

  • Last visited

  • Days Won

    19

Everything posted by bobh

  1. 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).
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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
  12. 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.
  13. 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?
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. Ibuprofen (aka advil, motrin) is for some (not all) a "resuce med" in a flare (you can't keep giving it indefinitely). It is definitely the case that some abx work and others not, and it varies from kid to kid and (likely?) by particular sickness for a child.. Haven't had the vomiting experience, but have had our fair share of mystery stomach aches. I have no experience with Colorado docs - am far away.
  19. Sorry to hear about you and your grandaughter's struggles. For several years, it was impossible for our child to get to school, because of his severe OCD. We chose to homeschool (mostly using online resources) - it was that or nothing. Different parents, and situations, have made for different coping mechanisms (e.g. type schooling in the search box at top right, once you are in this forum). If the issue is just October, you might approach the school for some kind of leniency/temporary school at home option. Many parents have had discussions with schools, with varying success with accomodations. It is quite a chore to educate schools on PANS/PANDAS - it depends on their previous experiences. By the way, probiotics consistently made our child worse. I have found this to be the case for a suprising number of PANS kids, but by no means all. Many kids aren't really checked for this (by on and off several times) - the assumption is often just "probiotics are helpful". Of course, that doesn't explain October, but our kid had lots of flares at different times and for different reasons, but regardless, his symptoms were less when he was off probiotics, whatever his current state.
  20. I've gotten a comment in another place where this is posted, that some might balk at the dropbox technology of the link in the post, and prefer to email data instead. By all means! My email address is also in the post. I am not expert in security, but for what it's worth, I believe that email is less secure than dropbox (i.e. it is easier for someone else to grab your data). To pretty much eliminate that problem, you could send it anonymously, which by email would mean creating or using an email address that can't be traced to you.
  21. You can see a list of 5 for Colorado here: http://pandasnetwork.org/us-providers/#COLORADO No guarantee that any of these will work out well - you might want to check for references or ratings some other way.
  22. Abdominal pain is so common among PANS kids. I recall seeing a video of Dr. K. (he's in Chicago) describing how they went down the esophagus on dozens (maybe over 100?) of PANS kids with a scope, trying to find something that might explain it - but they didn't find anything. Our kid had frequent stomach aches - but not continuous as you describe for your daughter. I have heard speculation (from one doctor that treats PANDAS/PANS) that a "reboot of the gut" by using antibiotics may be a good thing. And I have heard lots of talk on these kinds of pages (and facebook groups) about how bad abx is for the gut microbiome. If you are using a probiotic in between the abx doses, beware: some kids (mine, but others too) get worse on probiotics.
  23. You are invited to participate in a research study titled “Genetic Patterns Among PANS/PANDAS patients”. This study is being conducted by Bob Horvath, Mark Moeglein, 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 various autoimmune or immunological conditions and/or autism, all of which we suspect are related. The purpose of this study is to find out whether certain variations in DNA occur more commonly among PANS patients than the general population. If we find some, we will let you and many others see the (aggregate) results, and hope that a finding will spur further research into the biological processes, and ultimately, in the long term, possibilities for remedies for the disorder. Participation in this is entirely voluntary. You can choose not to participate at all, or to participate anonymously, or with your name attached to the data. Either way, there will be no effect on your relationship with the researchers, or any other negative consequences with not participating. You are being asked to take part in this study because you are a parent of a PANS/PANDAS child, or you are an adult that has suffered with PANS/PANDAS symptoms as a child, or as an adult. If you agree to participate, you will be asked to click on a link below and upload 23andMe or similar genetic data for one person (at this time, please don't upload multiple family members, just the one). You may also email your data (see below). The data will be collected regularly from the upload site, with a January 19th, 9pm EST cutoff time for data used in the study. Data uploaded after the cutoff time will be safely stored (with no direct identification of participants) on two computers only, for possible later confirmation of any result with the initial data. Even if you give your name, the data will not contain that name, but be coded before being processed. After the initial upload and the coding step, no other person, website or online service will have access to your data with your identification attached to it. Your data will be uploaded to GEDmatch (without your identification) in order to obtain ancestry, and to confirm no close relationships (>3%) to other participants. No genetic disease information will be extracted from participant data. For those that contribute anonymously, the only link between us 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 your anonymous data is if you contact myself (Bob Horvath) and reveal your fake name, so that I know which data to remove. This step could reveal your identity, but your data will be removed from the study. Study data will be stored without names in digital format. One copy will be on a computer in Ontario Canada, and another will be kept on a computer in Oregon, U.S.A. Only Bob Horvath and Mark Moeglein will have access to this full data. Aggregate results for the analysis of the data will later be made known publicly. There are no known risks associated with this study, beyond any risk there may be associated with the data existing (e.g. on the originating site, such as 23andMe). While you will not 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 PANS/PANDAS. 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 the link 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 the link. 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). https://www.dropbox.com/request/zrejlPbUjAnvN0OuK4Ny
  24. Oh, a loose or lost tooth is a very common flare source. That would be my bet.
  25. Our case is not the same as yours, but we were long term on probiotics (2+ years) before we discovered/proved that they were making our son's condition worse. So, you might try cutting those out, especially if it is not a recent add. We showed that well-known brands (not the kinds with strep) made him worse.
×
×
  • Create New...