New Turmoil Over Predicting the Effects of Genes

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TLEILAXU

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« on: April 24, 2019, 09:17:13 pm »
https://www.quantamagazine.org/new-turmoil-over-predicting-the-effects-of-genes-20190423/
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Various innovations in the field of genomics over the past few decades have given researchers hope that resolutions to long-lasting debates might finally be on the horizon. In particular, many have become optimistic about the prospects for disentangling the threads of “nature” and “nurture” — that is, about determining the extent to which genes alone can explain differences within and between populations.

But two recent studies are now calling some of the methods underlying those aspirations into question.

A key breakthrough was the recent development of genome-wide association studies (GWAS, commonly pronounced “gee-wahs”). The genetics of simple traits can often be deduced from pedigrees, and people have been using that approach for millennia to selectively breed vegetables that taste better and cows that produce more milk. But many traits are not the result of a handful of genes that have clear, strong effects; rather, they are the product of tens of thousands of weaker genetic signals, often found in noncoding DNA. When it comes to those kinds of features — the ones that scientists are most interested in, from height, to blood pressure, to predispositions for schizophrenia — a problem arises. Although environmental factors can be controlled in agricultural settings so as not to confound the search for genetic influences, it’s not so straightforward to extricate the two in humans.

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Given that some experts want to roll out polygenic scores in the clinic, it’s already clear that this flaw could deepen the disparity in health care. In a study published last month, researchers found that trying to translate insights gleaned from European data to make health predictions in people of African descent led to as much as a 4.5-fold drop in accuracy. Others have tried using polygenic scores to make poorly supported claims about differences in behavioral and social traits between populations (such as IQ and education attainment, which are far more difficult to define and unpack than height is, yet are being used to potentially inform future policymaking decisions). “It’s kind of scary,” said Sarah Tishkoff, a geneticist at the University of Pennsylvania who emphasized how critical it is to collect more underrepresented genomic information.


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« Reply #1 on: April 25, 2019, 01:42:16 pm »
Maybe it's something of the case that genetics and environment are both first and second-order effects?

In other words, neither is "the cause" even though it is somewhat trivially true that the genetics "comes before" the environment the genes will be in, really both the genes and environment are the "substrate of actualization?"  One necessarily actualizing the other, by turns.

OK, well, I am not sure what I even wrote there.  But it seems like something someone smart might say about this.
I am a warrior of ages, Anasurimbor. . . ages. I have dipped my nimil in a thousand hearts. I have ridden both against and for the No-God in the great wars that authored this wilderness. I have scaled the ramparts of great Golgotterath, watched the hearts of High Kings break for fury. -Cet'ingira

TLEILAXU

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« Reply #2 on: April 25, 2019, 01:57:54 pm »
Maybe it's something of the case that genetics and environment are both first and second-order effects?

In other words, neither is "the cause" even though it is somewhat trivially true that the genetics "comes before" the environment the genes will be in, really both the genes and environment are the "substrate of actualization?"  One necessarily actualizing the other, by turns.

OK, well, I am not sure what I even wrote there.  But it seems like something someone smart might say about this.
Haha I'm not sure either. It sounds exactly like something a philosopher would say. I think this quote helps answer it though.
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The eLife work underscores an urgent need for future studies to involve more people, a greater diversity in data and more family-based replication analyses. It also calls for more sophisticated statistical methods that can better control for population structure and other environmental factors — something researchers are already working on as they continue to delve into exactly what went wrong with the initial analyses. “The methods developed so far really think about genetics and environment as separate and orthogonal, as independent factors. When in truth, they’re not independent. The environment has had a strong impact on the genetics, and it probably interacts with the genetics,” said Gil McVean, a statistical geneticist at the University of Oxford. “We don’t really do a good job of … understanding [that] interaction.”

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« Reply #3 on: April 25, 2019, 02:28:43 pm »
Haha I'm not sure either. It sounds exactly like something a philosopher would say. I think this quote helps answer it though.

Well, as an idiot, I think that quote is basically saying the same thing.  Gene and the environment interplay to some degree.  I think the "end result" here might run into the problem of it being a complicated enough interaction, ultimately, that the simulation would just need to be the thing itself to really get "meaningful" results.  But maybe not, I guess we'll "see."
I am a warrior of ages, Anasurimbor. . . ages. I have dipped my nimil in a thousand hearts. I have ridden both against and for the No-God in the great wars that authored this wilderness. I have scaled the ramparts of great Golgotterath, watched the hearts of High Kings break for fury. -Cet'ingira