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The phenotypic legacy of admixture between modern humans and Neandertals [pdf] (gwern.net)
26 points by gwern on July 6, 2016 | hide | past | favorite | 12 comments

>Neandertal SNPs explained a significant [likelihood ratio test; false discovery rate (FDR) < 0.05 over all phenotype tests] percent of the risk in three traits in the E1 discovery cohort (Table 1): depression (2.03%,P = 0.0036), myocardial infarction (1.39%,P =0.0026), and corns and callosities (1.26%,P= 0.01). Neandertal SNPs also explained a nom-inally significant (P< 0.1) percent of risk for nine additional traits, including actinic and seborrheic keratosis, coronary atherosclerosis, and obesity (Table 1).

sounds like only obese/depressed/ill Neandertals agreed to interbreed with Cro-Magnons. May be being that picky is what did them?

It could also be an emergent property of the inter-breeding. Maybe those particular genes are fine in Neandertals, but combined with some Cro-Magnon genes leads to depression. I know that if you interbreed a lion and a tiger to make a "liger" the resulting hybrid grows to be larger than either lions or tigers; something similar could be happening here.

Take this in the spirit of fun facts, but the liger largeness phenomenon is not well described by the analogy "Maybe those particular genes are fine in Neandertals, but combined with some Cro-Magnon genes leads to depression".

Liger largeness (and the word "liger") is specific to the offspring of a male lion and a female tiger; the offspring of a male tiger and a female lion (a "tiglon" or "tigon") doesn't grow so large. What's going on is that lions rely on their mates being other lions -- male lions imprint their sperm in a way that promotes growth of the cub (which is a drain on the lioness's milk production) and female lions imprint their eggs so as to inhibit growth. It's not an interaction between lion genes and tiger genes that produces excessive growth, it is the male-imprinted lion genes failing to meet the female-imprinted genes they've evolved to rely on.

The same phenomenon (in terms of genetic arms race between the sexes -- it's phenotypically different) occurs in humans under the names Prader-Willi syndrome (maternal genes fail to meet paternal resistance) and Angelman Syndrome (other way around).

Just to nit pick Cro-Magnon people were the Eurasians that populated Europe after the hybridisation event(s) between Neanderthals and AMH.

We know from sequencing studies that they had a higher level of Neanderthal alleles than modern Europeans. Their larger brain size suggests a liger-like overshoot in brain growth given the constraints of the birth canal. I suspect Cro-Magnon women had an even more terrible time in childbirth than modern women.

Well the reason they are negative traits, is because that's the ones we keep track of in medical records.

Anyway all these traits are only slightly correlated with those conditions. Just because you have the depression genes, doesn't mean you will even likely have depression. It looks like only 2% get it.

They could also be reactions to modern environments. E.g. people get less sunlight, which means less vitamin D, which is linked to depression. Similar things with obesity, that would have been less common in prehistoric times, and is linked to many other conditions.

Although the traits are from medical records, the Neanderthal alleles could have shown protective effects against disease, not just increased risk, but they didn't.

It is more likely that the genes under selection which derived from Neanderthals in the Eurasian population are providing a positive selective advantage greater than the negative selection. For example, the alleles that increase the risk of depression may also result in higher intelligence. The way evolution works is what is present gets selected for or against and sometimes you have alleles that are both being selected for and against at the same time.

I have to say I don't like the weasel term anatomically modern humans to describe non-neanderthal people.

"anatomically modern human" is not a weasel word, it merely describes humans sharing anatomical features which arose ~ the last 200ka and are common to modern humans, in comparison to e.g. Neanderthals, who may very well have been cognitively modern but have common anatomical characteristics of earlier origin which distinguish them from all present day humans.

Yes it is. All humans now living are AMH so apart from being meaningless in the context of talking about the genetic history of the human population, it does not describe anything about the non-neanderthal populations. A much better term would be ancient African humans or even just African humans.

I thought the point of distinguishing them was that they didn't necessarily have language or modern intelligence. Just that their bones are similar.

Aside from the ascertainment bias Houshalter points out (look in records of pathology, you'll get genes linked to pathology), and the problem that genes from a relatively divergent species can be expected to often be harmful in another species, there's also a population genetics argument that Neandertals were genuinely less healthy on a genetic level because they had such a small population in Europe which makes it difficult for natural selection to purge all the mutations that constantly arise: http://biorxiv.org/content/early/2016/03/29/030387

This high-profile publication is interesting because it combines an evolutionary perspective with new approaches to analyzing electronic health records.

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