41 replies to this topic

[jack black]

Alright, anyone here with 23andme results and Social Anxiety also wiling to share their rs6685406 and rs10754855  polymorphisms?

 

OK, I have 3 results (myself and 2 other family members).

We are all AA for rs6685406 and all CC for rs10754855.

2 people have various degree of social anxiety and one is completely free of social anxiety, but has some generalized anxiety.

We are 97+% europeans with some minimal addition of other ethnicities.

So, what does it mean?

[littlePawn]

This is very interesting. if you told me rs6685406 was anything besides AA I would have dismissed my project. It's been a long time since I looked into it so I've forgotten the train of thought I was in and all the relevant information, but I identified that SNP in every sufferer of SA, and it only occurs in 12% of the population. This is very interesting. It could also be the case that not everyone who is AA has social anxiety, but that people that have social anxiety are AA.

 

Also I remember this rs had no clinical significance whatsoever. So no research directions focused on it in any papers that I could find. Thanks for the results, all we can do now is hope to collect more data and see if rs6685406 is present in those with SA, and not present in those without SA. If more data suggests this I'll look into this further

Edited by littlePawn, 11 May 2017 - 02:57 PM.

[sthira]

...I identified that SNP in every sufferer of SA, and it only occurs in 12% of the population. This is very interesting. It could also be the case that not everyone who is AA has social anxiety, but that people that have social anxiety are AA

Sorry to throw shade but I'm AG rs6685406, and suffer badly from social anxiety. Adding a second cliche to my comment: It could be that genetics loads the gun and environment pulls the trigger, blah blah.

Wouldn't it be nice to find a CURE?! Cures might be too much to ask from science, we reckon.

[littlePawn]

 

...I identified that SNP in every sufferer of SA, and it only occurs in 12% of the population. This is very interesting. It could also be the case that not everyone who is AA has social anxiety, but that people that have social anxiety are AA

Sorry to throw shade but I'm AG rs6685406, and suffer badly from social anxiety. Adding a second cliche to my comment: It could be that genetics loads the gun and environment pulls the trigger, blah blah.

Wouldn't it be nice to find a CURE?! Cures might be too much to ask from science, we reckon.

 

 

keep in mind the ancestral allele seems to be GG, so A could always mean you're heterozygous and still functioning less optimally with whatever this rs ultimately does (or not). Can we find someone with social anxiety who is GG to disprove this theory?

[jack black]

It's likely that SA is merely a phenotype and different mechanisms can lead to that. Just like different things can lead to let's say depression or liver cirrhosis. It would be too simplistic to expect SA be caused by one thing. Even if we find one SA case with GG it doesn't disprove the OP theory that SA is associated with A allele.

OP: have tried to ask that on some kind of 23&me forum?

[littlePawn]

Definitely agree jack. It seems to be that with conditions like social anxiety, autism and depression there are unknown interactions with different combinations of polymorphisms that may be triggers, but that unfortunately there are no individual polymorphisms definitely linked to any of these conditions. Rather they depend upon some complex combinations we don't yet understand where no individual rs is necessary for activating the disease.

 

That's a great idea about posting on the 23andme forum. I made a post there just now and will update this thread on how it goes. If we can see that SA sufferers have an A allele at a much higher frequency than non-SA sufferers, then it could show this rs is a piece to the puzzle. It's interesting because there is absolutely no literature on it last time I checked, and I'm not surprised either. As stated in my original post I genuinely believe most scientists aren't interested in even prioritizing finding cures, but rather are more interested in grant funding. Not their fault, but a fault of the modern institutionalized research system itself.

 

If I can find some link that hasn't been discovered yet, I'll get back into this project again, and perhaps we can work together on new ideas. But let's not get too excited yet, we'll await first the response we get from the 23andme forum post.

[jack black]

How did you come up with this idea in the first place?
And please keep us posted.

[littlePawn]

How did you come up with this idea in the first place?
And please keep us posted.

Studying biology and statistics through a textbook the idea just popped into my head. Why not find people with the same symptoms and identify if they have the same low pop freq. SNPs compared to people who don't.

 

 

Now, all I can say is I think we might be on to something. I've received private messages from others saying they have had chronic SA since being a child, and they all so far have an A allele or two. Have a read of this: https://www.23andmef...ufferers#latest

 

Looks like people who haven't had SA since birth are mostly GG. We must confirm that the pop frequency of AA is really 12% and not some mistake in the scientific literature. If that is the true pop frequency then I'm convinced this snp does play some critical role in SA.

 

This is very interesting. Interesting enough to re-familiarize myself where I was at 2 years ago with this idea. I can't see how this could be put down to luck. I'll find out more what gene this polymorphism is related to and whether it's known what function it plays. We'll also keep an eye on that thread at 23andMe and see if this hypothesis continues to be confirmed or not.

[jack black]

We must confirm that the pop frequency of AA is really 12% and not some mistake in the scientific literature.

 

 

i looked it up here: https://www.ncbi.nlm....cgi?rs=6685406

 

 

MAF/MinorAlleleCount:

A=0.3281/1643 (1000 Genomes)
A=0.3071/8943 (TOPMED)

looks like 2 sources and they are close. if i understand correctly, AA frequency would be A squared, about 9-11%.
 

[littlePawn]

Received more messages. AA correlated to SA since birth, GG not. I'm convinced this is something.

 

Next step: This rs seems to be related to the KAZN gene, a developmental gene. I've tried to research this gene however the literature is very scarce on what it actually does. Apparently its involved in desmosome assembly and cell adhesion etc (http://www.genecards...sp.pl?gene=KAZN). I can't find anything more about this gene than a single paragraph. Let alone what this rs does within the gene.

 

Disorders in related genes seem to be correlated with some cancers later in life, but no mention of any neurological issues such as SA. This isn't surprising since SA would be severely underreported and not a focus I'd imagine when looking at gene mutations by health researchers. Particularly in mice or human morbidity. 

 

Our next step: What else can we find out about the KAZN gene other than this single paragraph? Could we make some extrapolations from this besides general non-mental health risks? Any patterns in this description that could lead to neurological issues? Our next, next step if ever, would be to identify the actual pathway of synthesis this rs is weak in, and try supplementing the compound after this pathway. But that's far in the future before we know more what this gene does. 

 

Anyway I'll quote what we know so far about KAZN:

 

This gene encodes a protein that plays a role in desmosome assembly, cell adhesion, cytoskeletal organization, and epidermal differentiation. This protein co-localizes with desmoplakin and the cytolinker protein periplakin. In general, this protein localizes to the nucleus, desmosomes, cell membrane, and cortical actin-based structures. Some isoforms of this protein also associate with microtubules. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity has not been verified. 

[jack black]

 

Alright, anyone here with 23andme results and Social Anxiety also wiling to share their rs6685406 and rs10754855  polymorphisms?

 

OK, I have 3 results (myself and 2 other family members).

We are all AA for rs6685406 and all CC for rs10754855.

2 people have various degree of social anxiety and one is completely free of social anxiety, but has some generalized anxiety.

We are 97+% europeans with some minimal addition of other ethnicities.

So, what does it mean?

 

 

It just occurred to me i can contribute one more case to your study. he is the 4th member of my immediate family who didn't want to do the testing, but having the results of his parents (and there is no doubt about paternity), he must be also AA for rs6685406 and CC for rs10754855. he inherited mild social anxiety from one parent and mild generalized anxiety from another parent.

[littlePawn]

Thanks for that Jack