I used to think it was really interesting to attempt to turn all the human phenotypes into a list of underlying genotypes.
23&Me convinced me this process is mostly garbage. If at most you can conclude today that a complex phenotype has a complex underlying genotype: you're just confirming what we knew two decades ago, and not providing any useful answers for how the complex phenotypes come about, just that variations of the genotype lead to somewhat different outcomes. Totally boring.
You're assuming that associations to blocks of linked genotype is the end of the story.
Yes, an association to a phenotype using data like that sourced from 23&me only generally points in the direction of the genes and snvs which cause alterations in phenotype, but that is just a stepping stone.
It narrows down the search space to about 1-2% of the genome, which then follow up studies can fine map. Using high resolution data, such as whole-genome or exome sequence, you can then pinpoint protein-coding changes which alter phenotype. This is what a lot of people are doing right now, using the last decade of GWAS results to fine map using WGS.
If you discover exactly how the machine breaks, it is a lot easier to fix it, or at least prevent it from getting broken in the first place.
It is not a simple as flipping one switch, and it is an incremental 'boring' process, but the potential to better understand disease today and in the future is worth its weight in gold.
These are organismal phenotypes which have no direct correlate to molecular phenotypes (because they are complex and caused by entirely nontrivial developmental processes). Even if you knew the proteins involved you couldn't craft a realistic model that explained the observed organismal trait from the protein variations using any amount of existing scientific methods.
Obviously this isn't true for some diseases, such as simple mendelian diseases caused by single SNP changes.
I worked in the field for decades and very little progress has been made mapping genotype to complex organismal phenotypes or appreciating how complex development processes are affected by collections of mutations. This specific research, even if wildly successful, wouldn't really have impact on any significant diseases.
Personally, I find this study boring (or interesting, depending on your take) for an entirely different reason: this trait is only 15% heritable. Thus, almost all variation in your ability to maintain a beat is learned from your environment. There’s hope for us all!
Also — Even for that 15%, how much of that is also nurture? Musical parents rock their kids to a beat, play and sing music, etc… I’m not sure if this is mentioned in the study, but this would be nearly impossible to control for.
"reared apart twins" studies to the rescue! though it would probably take a loooong time to get a sample size that has actually some statistical power.
This reminds of a previous music study. The professor teaching my genetics class in grad school said he thought that musical ability was heritable- look at all the children of musicians who are good at music! Several of us sort of looked at each other like "did he really just say that and not think that perhaps exposure to labelled examples during a time of neural plasticity would dominate?"
Just because 85% is environmental doesn't mean that there's hope for us all. It's a common mistake to think of genes as unable to be changed and environment to be changed. But, for example, maybe if your mother smokes during pregnancy, it inhibits the part of your brain that handles beat. In that case, the trait is environmental AND innate. For another example think of one-armedness. Most people with one arm will have lost it in an accident, the fact that the trait isn't genetic doesn't mean there is hope for them to have a second arm.
Conversely, that a trait is very heritable doesn't mean there isn't hope for us. Language and dialect are very heritable, but we can learn new languages and even adapt our dialect.
Even if something is actually "genetically" heritable, we don't how heritable it would be over the space of all possible environments, just the ones we test.
Entrainment is an intrinsic phenomena of powered oscillators. That’s why entrainment is pervasive in the brain and body. For instance, heart beats are entrained by rhythms in the spinal cord.
But that’s also (probably) why most animals don’t entrain to a beat—it would be very dangerous to allow oneself to be entrained by external rhythms, even from conspecifics (same species).
Humans are also bad at entraining to a beat when stressed — you gotta relax to dance. That’s why a little alcohol (or other drugs) can vastly enhance one’s propensity to synchronize to a beat.
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[ 1.8 ms ] story [ 55.2 ms ] thread23&Me convinced me this process is mostly garbage. If at most you can conclude today that a complex phenotype has a complex underlying genotype: you're just confirming what we knew two decades ago, and not providing any useful answers for how the complex phenotypes come about, just that variations of the genotype lead to somewhat different outcomes. Totally boring.
Yes, an association to a phenotype using data like that sourced from 23&me only generally points in the direction of the genes and snvs which cause alterations in phenotype, but that is just a stepping stone.
It narrows down the search space to about 1-2% of the genome, which then follow up studies can fine map. Using high resolution data, such as whole-genome or exome sequence, you can then pinpoint protein-coding changes which alter phenotype. This is what a lot of people are doing right now, using the last decade of GWAS results to fine map using WGS.
If you discover exactly how the machine breaks, it is a lot easier to fix it, or at least prevent it from getting broken in the first place.
It is not a simple as flipping one switch, and it is an incremental 'boring' process, but the potential to better understand disease today and in the future is worth its weight in gold.
Obviously this isn't true for some diseases, such as simple mendelian diseases caused by single SNP changes.
I worked in the field for decades and very little progress has been made mapping genotype to complex organismal phenotypes or appreciating how complex development processes are affected by collections of mutations. This specific research, even if wildly successful, wouldn't really have impact on any significant diseases.
Even if something is actually "genetically" heritable, we don't how heritable it would be over the space of all possible environments, just the ones we test.
They looked at what genes are correlated with
> of musical beat synchronization
an ability to keep the beat in music
> demonstrates high polygenicity
and found that it's a trait caused by a bunch of genes in some complex makeup, not just one.
But that’s also (probably) why most animals don’t entrain to a beat—it would be very dangerous to allow oneself to be entrained by external rhythms, even from conspecifics (same species).
Humans are also bad at entraining to a beat when stressed — you gotta relax to dance. That’s why a little alcohol (or other drugs) can vastly enhance one’s propensity to synchronize to a beat.
For more, see this recent article on human resonance phenomena: https://www.frontiersin.org/articles/10.3389/fnbot.2022.8504...