Every Gene Affects Every Trait, So Personalized/genomic Medicine Is Doomed

haidut

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As one of the article says, there has been a boom in the so-called genome-wide association studies over the last decade. However, these studies have resulted in no reliable leads for genetic causes of disease. A new study at Stanford suggests that the reason this is so is that in fact ALL genes may be involved in contributing to health/disease even though the effects of the entire genome is manifested through a much smaller group of genes called "core genes" related to a specific trait or pathology. If that is true then at best personalized/genomic medicine, which has been sucking billions in taxpayer's money, is currently impossible. And at worst the whole idea of genes as controllers of our health and physical traits may have to be scrapped altogether. Namely, changing/controlling a trait or disease would require not only precisely fine-tuning the activity of ALL genes in a person's genome, but this calibration has to be done continuously as environmental condition and thus methylation patterns change on a daily basis. Most geneticists that I have talked to have been getting increasingly pessimistic about their career choice unless they work at NIH, which has been getting billions in funding to continue pursuing the genetic "silver bullet".
Hey @Drareg, @Such_Saturation and @jaa - I think you will find this interesting.

http://www.cell.com/cell/fulltext/S0092-8674(17)30629-3

http://gizmodo.com/this-study-is-forcing-scientists-to-rethink-the-human-g-1796172648
"...As both genetic sequencing has gotten cheaper and computerized data analysis has gotten better, more and more researchers have turned to what are known as genome-wide association studies in hopes of sussing out which individual genes are associated with particular disorders. The logic here is simple: If you have a whole lot of people with a disease, you should be able to tell what genetic traits those people have in common that might be responsible. This thinking has resulted in an entire catalogue of hundreds of research studies that has shed light on the genetic origins of diseases such as type 2 diabetes, Parkinson’s disease, Crohn’s disease, and prostate cancer, while helping fuel the rise of personalized medicine. Now, though, a new analysis calls the entire approach into question."

"...Their analysis suggests an intriguing new way of viewing the genome in which nearly every gene impacts every other gene. Instead of a system in which you can plug and play different variables to affect different results, it’s a complex, inter-related network. They call this the “omnigenic model.” Their work has broad, sweeping implications for the entire field of genetics. First off, that all those big, expensive genome-wide association studies may wind up being little more than a waste of time because they turn up genetic variants that, while perhaps interconnected to the disease, may not actually point to a viable target for things like drug therapy. Indeed, genes that often seem related to diseases have stumped researchers in terms of the role they actually play in the condition. In the paper, for example, the Stanford researchers re-analysed a 2014 study of 250,000 people which found nearly 700 DNA variants linked to height—but only 16 percent of these variants had anything to do with a person’s height. In the paper, the Stanford researchers suggest that the impact of each variant has a teeny impact on height."

What If (Almost) Every Gene Affects (Almost) Everything?
"...Yes, he says, there will be “core genes” that follow this pattern. They will affect traits in ways that make biological sense. But genes don’t work in isolation. They influence each other in large networks, so that “if a variant changes any one gene, it could change an entire gene network,” says Boyle. He believes that these networks are so thoroughly interconnected that every gene is just a few degrees of separation away from every other. Which means that changes in basically any gene will ripple inwards to affect the core genes for a particular trait. The Stanford trio call this the “omnigenic model.” In the simplest terms, they’re saying that most genes matter for most things."

"...The team found more evidence for their omnigenic model by analyzing other large genetic studies of rheumatoid arthritis, schizophrenia, and Crohn’s disease. Many of the variants identified by these studies seem relevant to the disease in question. For example, some of the schizophrenia variants affect genes involved in the nervous system. But mostly, the variants affect genes that don’t make for compelling stories, and that do pretty generic things. According to the omnigenic model, they’re only contributing to the risk of disease in incidental ways, by rippling across to the more relevant core genes. “It’s the only model I can come up with that make all the data fit,” Pritchard says."

"...If Pritchard is right, it has big implications for genetics as a field. Geneticists are running ever-bigger and more expensive searches to identify the variants behind all kinds of traits and diseases, in the specific hope that their results will tell them something biologically interesting. They could show us more about how our bodies develop, for example, or point to new approaches for treating disease. But if Pritchard is right, then most variants will not provide such leads because they exert their influence in incidental ways."

"...Put it this way: The Atlantic is produced by all of us who work here, but our lives are also affected by all the people we encounter—friends, roommates, partners, taxi drivers, passers-by etc. If you listed everyone who influences what happens at The Atlantic, even in small ways, all of those peripheral people would show up on the list. But almost none of them would tell you much about how we do journalism. They're important, but also not actually that relevant. Pritchard thinks the same is true for our genes. And if that’s the case, he says, “it’s not clear to me that increasing your study size is going to help very much.”"
 
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Why the hell is GMO GRAS, LOL
 

Simonsays

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Bet theyre not looking for the gene or "genes" for obdurate stubborness in the face of results which seems particularly prevalent in geneticists working at NIH or the gene for " i know its a waste of time but its a job for life" , ill stop now, as my cynical gene has kicked in.
 

Regina

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Bet theyre not looking for the gene or "genes" for obdurate stubborness in the face of results which seems particularly prevalent in geneticists working at NIH or the gene for " i know its a waste of time but its a job for life" , ill stop now, as my cynical gene has kicked in.
Yea. We are doomed to meaning...
 
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Personalized medicine seems to be built on the assumption that medicine is the answer.

answer for what??

type 2 diabetes, Parkinson’s disease, Crohn’s disease, and prostate cancer,

oh.

No.
 

Drareg

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It's rehashed fraud,it's similar nonsense that the"scientific" "rational" nazis used a few decades ago,what's worrying is before the nazis and throughout history similar "knowledge authorities"were at this,the behaviour is ingrained into humans and Im guessing it's "Peaty" processes driving the stream of consciousness and behaviour like serotonin et al.
Google have been influencing "gene searches" for years,assisting the pumping of the view of gene being solely responsible for everything,23 and me owned by Google creators wife of course.

GWAS is being used for fraud and pathological racism,researchers like Plomin are psychopathically obsessed with twin studies and heritability of IQ scores,the reason all these arguments are popping up in red piller angry failed at capitalism boys and girls stream of consciousness is because they know the theory has been debunked again,they are given it a big last pump(plomin etc) they have a desire for societies based on racial hierarchy or hilariously their desire for high IQ types becoming the new entitled class of our world future,a bit like the old inherited wealth types like Galton who sits on his **** picking choosing what he will look at while a slave clean his underwear, a bit like a modern academic speculating about inferior humans for the ultimate stress free lifestyle,the red pillers have run out of biological energy to achieve captilist ambitions now want the directors role of low energy dictating to everyone from the throne of high IQ(Galton and contemporary academics)
Take note of the rise of cyber beggars(patreon via YouTube)pumping the IQ -gene "hypothesis" (delusion),mania fuelled fools are manically correlating anything that pumps the view,this capacity within their cult is seen as "intelligent",it's the equivalent of a child sticking triangles in the triangle shape hole.
The other beggars/government welfare cases(grants)are the Professors mainly in psychology in tenure making a living from said fraud.

Even more hilarious is attempting to correlate genes and IQ scores with societal success,high IQ types become doctors don't you know,being a "realist" here then we must acknowledge iatrogenics the fact that doctors are killing people,well they become lawyers too,help enforce corrupt legislation as a means to stifle human development and kill people.
Oh but what about professors in tenure with 3 months off every summer =nuclear bomb etc etc
Lower East Asian countries are the highest IQs don't ya know,full blown authoritarian,astronomic suicide rates and execute people in vans on the side of the street Execution van - Wikipedia
They also breath very little oxygen because they live in a polluted atmosphere etc etc ,genius! Oh don't forget child abuse of all kinds in particular child sex abuse ,off the charts in both western and severely under reported and supresseed in lower east Asia.
How the above behaviour can make these western and eastern people believe they are superior to the African bushmen is beyond me.
So high IQ types succeed in a psychotic mentally ill contemporary world where majority of great advancements were a fluke.
We then refer to those who don't succeed in said world or adopt said systems and appear dysfunctional as low IQ when in reality they are more coherent with nature and less psychotic,they may become psychotic as they are stressed and hoodwinked into become westernised or lower East Asian like.
Its real intelligent and High IQ to put yourself into financial debt for a degree in an authoritarian styled job within an authoritarian society that will pat you on the back and socially create a paradigm that says your smart even if the guy who can't spell eduction is worth more than a Professor in tenure or Doctor by engaging in trading goods.


Below is a good study to look at and keep in mind the billions Haidut mentioned when the delusional psychotics are claiming research isn't funded or it's an uncomfortable truth/inheritance that people don't speak about.
"HERITABILITY STUDIES IN THE POSTGENOMIC ERA: THE FATAL FLAW IS CONCEPTUAL"
HERITABILITY STUDIES IN THE POSTGENOMIC ERA: THE FATAL FLAW IS CONCEPTUAL

"Barnes et al. (2014) wrote a response to our article. In their response (and now re- joinder in this issue, Wright et al., 2015), they adopted a strategy common to behav- ioral geneticists, which Panofsky (2014: 141) called, “hitting them over the head style.” This approach involves dodging criticisms by misrepresenting arguments and insinuating that critics are politically motivated and reject scientific truths as well as focusing on a few “‘tractable’ empirical objections” while “ignoring the deeper theoretical objections” (Panofsky, 2014: 152). As Panofsky (2014: 144) noted: “‘Hitting them over the head’ was a strategy for building scientific capital that involved constructing one’s intellectual interlocutors as mortal enemies and attacking them in spectacular, polemical fashion”; “the task was not to seek synthesis, integration, or sober rational persuasion but to en- gage in polemical scientific attack, declaring themselves as crusaders who would rout the antigenetics heresy gripping behavioral science”
 

jaa

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Interesting stuff. That really throws a monkey wrench into gene editing. Thanks for the alert haidut.
 

snowboard111

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All these genes things are all just scam to funnel money wherever they want... For all that matters, all the "scientist" at the NIH have been playing tic-tac-toe for the last 27 years. They are sharing they "discoveries" mostly with the agro-industry. They didn't know what to do next; So let's tackle the microbiome. They are trillions of them and they are very important... so we need billions to identify them.

Same scam, different subject. Meanwhile, the best route they came up with is that we should agree that we must mix with technology to stay healthy or humanly relevant. You have to laugh... :bag:
 

Tenacity

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I feel that Darwin has something very relevant to say in relationship to this thread, from his On The Origin of Species. He seemed to be aware of this way in advance of the discovery of genes.

"There are many laws regarding variation, some few of which can be dimly seen, and will hereafter be briefly mentioned. I will here only allude to what may be called correlation of growth. Any change in the embryo or larva will almost certainly entail changes in the mature animal. In monstrosities, the correlations between quite distinct parts are very curious; and many instances are given in Isidore Geoffrey St Hilaire's great work on this subject. Breeders believe that long limbs are almost always accompanied by an elongated head. Some instances of correlation are quite whimsical; thus cats with blue eyes are invariably deaf; colour and constitutional peculiarities go together, of which many remarkable cases could be given amongst animals and plants. From the facts collected by Heusinger, it appears that white sheep and pigs are differently affected from coloured individuals by certain vegetable poisons. Hairless dogs have imperfect teeth; long-haired and coarse-haired animals are apt to have, as is asserted, long or many horns; pigeons with feathered feet have skin between their outer toes; pigeons with short beaks have small feet, and those with long beaks large feet. Hence, if man goes on selecting, and thus augmenting, any peculiariy, he will almost certainly unconsciously modify other parts of the structure, owing to the msysterious laws of the correlation of growth."
 

Dante

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Google have been influencing "gene searches" for years,assisting the pumping of the view of gene being solely responsible for everything,23 and me owned by Google creators wife of course.

Oh but what about professors in tenure with 3 months off every summer =nuclear bomb etc etc

Its real intelligent and High IQ to put yourself into financial debt for a degree in an authoritarian styled job within an authoritarian society that will pat you on the back and socially create a paradigm that says your smart even if the guy who can't spell eduction is worth more than a Professor in tenure or Doctor by engaging in trading goods.
Hey drareg,
Regarding the Google influencing "gene searches" , are you sure ? I think the genetic view lands simply in the first page because it's the dominant view in mainstream biology . ( For example when I type the word "genetic testing" ,Google , bing( Microsoft search engine) and Yahoo all show 23andMe in their first page(so it's not just Google). Plus Google upgraded their search algorithm in 2015(RankBrain) if I remember correctly.
A digression but in the pre-internet era ,what would a guy/girl do if he/she wanted to learn , let's say ,maths/physics and wanted to collaborate with like minded people? He would have no choice but to go to college and become a professor. Pollack is also a professor at University of Washington afaik.
 

Drareg

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Hey drareg,
Regarding the Google influencing "gene searches" , are you sure ? I think the genetic view lands simply in the first page because it's the dominant view in mainstream biology . ( For example when I type the word "genetic testing" ,Google , bing( Microsoft search engine) and Yahoo all show 23andMe in their first page(so it's not just Google). Plus Google upgraded their search algorithm in 2015(RankBrain) if I remember correctly.
A digression but in the pre-internet era ,what would a guy/girl do if he/she wanted to learn , let's say ,maths/physics and wanted to collaborate with like minded people? He would have no choice but to go to college and become a professor. Pollack is also a professor at University of Washington afaik.

Great point! Don't forget Peat went to university also!

My post though is satirical for the most part,I'm aiming at those who pump the view of iq and genetics and their reasoning,they claim going to college is intelligent behaviour compared to not going,in modern times this is not the case in general with the current dogmas and cost of attendance present in academia,your more likely to benefit from the in a university library ,seems expensive just for that.
Pollack would probably have a lot to say about the politics in academia and also with grants.
There are exceptions,I'm sure those who Pollack teaches learn a lot but they would probably learn a ton more if Pollack was independent and financially capable of doing his work without "the boards" hovering over the terminology he uses.

With that in mind before the Internet many did do extremely well without university,Da Vinci is always a cliched example but it points in the direction I'm getting at,he believed in observing the world around him.
Maybe that's what Blake College would have become,a place to decode and uneducate yourself and learn to perceive as a human can and should.

There are currently no hard facts for Google influencing searches for genetics,this is my speculation,I mentioned it in a previous thread before the below article came out,it's about shopping but it highlights googles actions and behaviours.
Independent people can infleucne searches/traffic also.
European Union fines Google a record $2.7 billion for stifling online shopping competitors
 
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So is this basically showing that the only way genetic engineering would be highly successful is if it's done from an approach of all genes as an interconnected network, rather than something more like the senolytic/anti-aging approach? The idea in that is to "target" aging and erase it -- but if all genes actually are interconnected, how would one reasonably expect to target any actual problem then? If it requires a network-wide, larger-scale approach rather than an individualized and selective one, it would mean the process is likely to be way more difficult and troublesome. I liked the idea better at selective gene/gene therapies because it sounds much more feasible -- this approach sounds like it would require taking a step back/going back to the drawing board of the approach to gene interventions if you look at it this way.

I'm kind of at a standstill though since there is positive research and results associated with senolytics and aging in trials, which does take on a more gene-specific approach than a gene-network wide approach to gene alterations. In any case the process is well beyond my comprehension here, but it's still really interesting to me.
 

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