‘Key player’ identified in genetic link to psychiatric conditions(cardiff.ac.uk)
cardiff.ac.uk
‘Key player’ identified in genetic link to psychiatric conditions
https://www.cardiff.ac.uk/news/view/1566294-key-player-identified-in-genetic-link-to-psychiatric-conditions
10 comments
Suppose I learn person X is missing CYFIP1. Could on use crisper to put it back? Where would I get a CYFIP1 for X? Are the dna bases really the same person to person?
Can we use 23andme data to see if we've this gene?
It really depends. In this article, they describe a complex genetic architecture, with copy number variations (the entire gene exists in multiple copies along the genome) as well as deletions and insertions. 23andme data, being based on microarrays, probably gives a misleading read on this because the complex genetic architecture is not encoded into the microarray.
I generally recommend against reading primary liuterature or the PR around it and immediately checking genetic tests to see if you "have this disorder". IN complex diseases, many genotypes have low penetrance (IE, the genotype variable is only weakly correlated with the phenotype label), and diseases like this are complex, polygenic, and any individual mutations only partially explain the visible phenotype.
I generally recommend against reading primary liuterature or the PR around it and immediately checking genetic tests to see if you "have this disorder". IN complex diseases, many genotypes have low penetrance (IE, the genotype variable is only weakly correlated with the phenotype label), and diseases like this are complex, polygenic, and any individual mutations only partially explain the visible phenotype.
Perhaps a stupid question (as I am neither very educated on the topic of genetics nor have I used 23andme myself), but isn't there a way to download the dump of your raw genome data (that is compatible with all the other genetic analysis tools out there) from 23andme that would allow you to find it?
Btw fully agreed with you on the points of complexity and regular people misinterpreting their results following the PR hype.
Btw fully agreed with you on the points of complexity and regular people misinterpreting their results following the PR hype.
When you download that dump from 23andme, unless you signed up for whole genome sequencing, and even then, the dump will not include high resolution data which would allow you to analyze these results in the context of the paper.
If you did WGS (whole genome sequencing), you might be able to take the VCF files (or the FASTQ) and, hopefully, their mapping process did an accurate job computing your individual genotype. However, in cases like this with CNVs and indels, I wouldn't really trust the assembly. MOst of the tools that we built to produce genotypes get a lot of the details of the mapping or assembly wrong. You could do a lot better if you had your genome sequencing using both long and short read tech, and used the long reads to make a reliable scaffold and then mapped the short reads, but with CNVs, much of that is still guesswork.
If you did WGS (whole genome sequencing), you might be able to take the VCF files (or the FASTQ) and, hopefully, their mapping process did an accurate job computing your individual genotype. However, in cases like this with CNVs and indels, I wouldn't really trust the assembly. MOst of the tools that we built to produce genotypes get a lot of the details of the mapping or assembly wrong. You could do a lot better if you had your genome sequencing using both long and short read tech, and used the long reads to make a reliable scaffold and then mapped the short reads, but with CNVs, much of that is still guesswork.
> Most of the tools that we built to produce genotypes get a lot of the details of the mapping or assembly wrong.
Can't you use the existing reference human genome as a scaffold?
Can't you use the existing reference human genome as a scaffold?
not if somebody has a complex genetic architecture with differences in areas of high self-similarity, or copy number. The reference lacks areas (and has areas) that are in or completely missing in other human populations. It took people decades to acknowledge this deficiency (which is due almost entirely to using a very limited sampling of humans for the first references).
Ah, that clarifies it, thank you. I didn't realize that the raw dumps on 23andme would differ depending on which version of the product you paid for, as well as the inherent imprecision of those.
If you want a high quality genome (ilumina UYG) to start with, it's https://my.pgp-hms.org/profile/hu80855C
which includes the original BAM files (so you can try your own mapping) as well as called variants (conveniently[?] segregated into SNPs and indels).
I would expect "everything" you need (except for long reads) is here for you to determine if the owner of that genotype (I can vouch for them...) has the genetic alterations described in this article (https://www.nature.com/articles/s41467-019-11119-7) after performing some sort of magical rat/human remapping (tricky) or referencing off of https://www.omim.org/entry/615656
I would be impressed if somebody could actually make a clinically actionable recommendation for this genome, as Illumina described it as have zero known risk.
I would expect "everything" you need (except for long reads) is here for you to determine if the owner of that genotype (I can vouch for them...) has the genetic alterations described in this article (https://www.nature.com/articles/s41467-019-11119-7) after performing some sort of magical rat/human remapping (tricky) or referencing off of https://www.omim.org/entry/615656
I would be impressed if somebody could actually make a clinically actionable recommendation for this genome, as Illumina described it as have zero known risk.
If the results of this study are confirmed, I sincerely hope CYFIP1 becomes at least colloquially known as The Andrew Wakefield Gene.
Explain
Andrew Wakefield[0] is a disgraced and discredited former doctor who authored a fraudulent research paper in prestigious medical journal The Lancet which claimed a link between the MMR vaccine and autism.
Wakefield's "study" led to a decline in vaccination rates in the US, the UK, and likely several other countries, and has resulted in serious illnesses and deaths.
[0]: https://en.wikipedia.org/wiki/Andrew_Wakefield
Wakefield's "study" led to a decline in vaccination rates in the US, the UK, and likely several other countries, and has resulted in serious illnesses and deaths.
[0]: https://en.wikipedia.org/wiki/Andrew_Wakefield
I am guessing that naming the gene after him is a sort of sarcastic rejoinder - a bit like naming a line of meridian after a flat earther?
I get it but there are dozens of not hundreds of people who have put in decades of work each to discover and enhance our understanding of this gene and its medical links - they would be better candidates. Or perhaps they could choose to name it.
But celebrating a fraud and "fake news" founder ... even sarcastically does not sit right with me.
Happily I saw a dog turd on the street a while back - we could name that after Wakefield. Perhaps put it on Google maps.
I get it but there are dozens of not hundreds of people who have put in decades of work each to discover and enhance our understanding of this gene and its medical links - they would be better candidates. Or perhaps they could choose to name it.
But celebrating a fraud and "fake news" founder ... even sarcastically does not sit right with me.
Happily I saw a dog turd on the street a while back - we could name that after Wakefield. Perhaps put it on Google maps.
It would be more than that.
Wakefield is a guiding light name in the anti-vacc community. This would severely water down the effectiveness of his name...
And especially in todays search engine driven world of "self education" that could be amazingly effective.
And especially in todays search engine driven world of "self education" that could be amazingly effective.
That was the angle I was going for, yes. And I agree, it’s not great to name the finding after something negative, but I don’t know how better to keep that kind of evil in the minds of the general population. I want to illuminate this like I want to illuminate other historical evils such as Fascism and Communism.
I'm having a hard time understanding what Andrew Wakefield has to do with the CYFIP1's role. The wikipedia post does not mention it at all. Can someone explain what Wakefield has to do with it?
As far as I understand, he doesn’t. The point being that the aforementioned gene might be confirmed as the cause of autism, and this would remind the general population that the link claimed by Wakefield between MMR vaccines and autism was completely fraudulent, and that people died as a result.
What was his motive to publish such paper?
That's the guy who "discovered" that vaccines were causing autism.
According to GeneCards, these diseases are related to this gene for quite some time:
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CYFIP1
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CYFIP1
First time I stumble upon this website (GenesCard). It shows how extensive the shared human knowledge is about genes and how little I know!
And also this website is full of useful data HN people can use for playing with ML. Thanks for sharing !
Well, if you want to use this data to "play" with ML, then you also need an annotated dataset for at least say 100 individuals.
They hadn't identified the causal mutation, as far as I understand it, just the general vicinity in terms of linkage disequilibrium.
The title is quite an exaggeration for the paper.
There was a post on slatestarcodex [1] a while back that talked about various models/conceptions of both schizophrenia and autism as well as the associated personality traits etc., which I found quite interesting.
1. https://slatestarcodex.com/2018/12/11/diametrical-model-of-a...
1. https://slatestarcodex.com/2018/12/11/diametrical-model-of-a...
Not sure how I feel about this implication that schizophrenia and autism are opposite issues on the same axis; there's existing evidence that schizotypy and autism are actually considered quite similar. The schizotypal personality disorder mentioned must actually be diagnosed via a ruling out of autism, as they both have similar symptoms and score similarly in socio-cognitive testing (eg. facial emotion recognition).
EDIT: Also, given that schizotypal personality disorder scores similarly to autism in recognizing human facial expressions, I'm not entirely sure where the author in the link is getting the depiction of a schizotypal person being particularly socially insightful through an examination of facial feature (the provided example being how to extrapolate from an eye twitch).
EDIT: Also, given that schizotypal personality disorder scores similarly to autism in recognizing human facial expressions, I'm not entirely sure where the author in the link is getting the depiction of a schizotypal person being particularly socially insightful through an examination of facial feature (the provided example being how to extrapolate from an eye twitch).
Dollars to donuts industry will use this to screen employees, insurance companies will use it to deny coverage, and people won’t date you without a prescreen. I’m almost to the point that I fear any new technology by default because I immediately think of all the ways society could turn it towards evil.
Paraphrasing Einstein our capacity for increases in human knowledge far outweighs our capacity for increases in human compassion.
Paraphrasing Einstein our capacity for increases in human knowledge far outweighs our capacity for increases in human compassion.
> people won’t date you without a prescreen
Most people don't do that for STIs today so why would they do it for genetic predisposition of heritable diseases?
Most people don't do that for STIs today so why would they do it for genetic predisposition of heritable diseases?
Hell, pre-screening as a concept was taught to me in a biology class 10+ years ago with one example being (some) Jewish communities implementing genetic counseling as a pre-screen before marriage to avoid unwell offspring, e.g. Tay-Sachs. Organizations[0] exist for this purpose already.
The ethics of this as a situation was taught by watching and discussing Gattaca, a movie from 1997.
Certainly not a new idea nor concern. It is a reality, though not quite widespread. Perhaps we will open new societal cans of worm through mass-market, rapid screening. As I write this, somewhat reminds me of the internet.
[0] - https://en.wikipedia.org/wiki/Dor_Yeshorim
The ethics of this as a situation was taught by watching and discussing Gattaca, a movie from 1997.
Certainly not a new idea nor concern. It is a reality, though not quite widespread. Perhaps we will open new societal cans of worm through mass-market, rapid screening. As I write this, somewhat reminds me of the internet.
[0] - https://en.wikipedia.org/wiki/Dor_Yeshorim
It's currently illegal in the US to use genetics for screening for health insurance (legal for life insurance).
Maybe your fear that new tech will be used for evil is coming from all the negative articles which immediately jump to assuming things will be used "for evil".
Maybe your fear that new tech will be used for evil is coming from all the negative articles which immediately jump to assuming things will be used "for evil".
yawn, another overreaching PR piece. psychiatric conditions are massively polygenic and even the idea of driver causal mutations is suspect.