Human evolution; traits from many points in DNA (Introduction)

by David Turell @, Friday, May 17, 2019, 18:26 (64 days ago) @ David Turell

Very hard to analyze:

https://www.quantamagazine.org/new-turmoil-over-predicting-the-effects-of-genes-20190423/

"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.

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"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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"two results published last month have cast doubt on those findings, and have illustrated that problems with interpretations of GWAS results are far more pervasive than anyone realized. The work has implications for how scientists think about the interactions between genetic and environmental effects. It also “raise[s] the ghosts of the possibility that we overestimate … how important genetics is in contributing to differences between people,” said Rasmus Nielsen, a biologist at the University of California, Berkeley.

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"Five years ago, a series of analyses on a European database made these dreams seem within reach. People of northern European ancestry are on average taller than those of southern European ancestry. Researchers wanted to explore whether those differences were a result of natural selection. They found that the polygenic scores for height did indeed increase from southern to northern Europe, much more so than would be expected from the random fluctuations in variant frequencies called genetic drift.

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"But the scientists had ways to correct for those biases, and the signal of selection on height remained. “We were really excited about that, because we were finally getting to look at … adaptation operating on complex traits,” said Graham Coop,

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“'The new studies are really quite disconcerting,” Barton said, because they demonstrated that scientists had been mistaking biases in the polygenic score calculations for something biologically interesting. Their statistical methods of accounting for population structure were not so adequate after all.

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"Barton agreed. “The whole thing is tricky, because the origins of genetic variation in any population are really complicated,” he said. “Now you really can’t take at face value any of these methods over the last four or five years that use polygenic scores.”

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“'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.'”

Comment: We really do not know how genes control traits. Environment plays an unknown degree of influence, as dhw notes Obviously the whole of DNA is involved; no support for the concept of 'junk'.


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