But soon after the study’s high-profile launch on 24 August, autistic people and some ASD researchers expressed concern that it had gone ahead without meaningfully consulting the autism community. Fears about the sharing of genetic data and an alleged failure to properly explain the benefits of the research have been raised by a group called Boycott Spectrum 10K, which is led by autistic people. The group plans to protest outside the ARC premises in Cambridge in October. A separate petition against the study gathered more than 5,000 signatures.
Damian Milton, a researcher in intellectual and developmental disabilities at the University of Kent in Canterbury, UK, is one of those who signed the Boycott Spectrum 10K petition. Milton has been diagnosed with Asperger’s syndrome, a form of ASD. He says it is not clear how the study will improve participants’ well-being, and its “aim seems to be more about collecting DNA samples and data sharing”.
As a result of the backlash, the Spectrum 10K team paused the study on 10 September, apologized for causing distress, and promised a deeper consultation with autistic people and their families.
I assume they’ll restart, but this sort of research will happen somewhere. Autism is a reasonably heritable trait, and many of the people with autism are not “high functioning.”
Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response.
You can find the SNP in you 23andMe raw data (unless you are on the recent chip; I looked for a tag variant but found none). If I’m reading the paper correctly, having the AA genotype increases your risk of severe COVID-19 by an odds of 1.58, all things equal. Not crazy bad, but not great either. The haplotype that carries the G allele in non-Africans seems to come from Neanderthals. In Africa, the ancestral G is the majority, though a minority of individuals are A, and that was passed on to Eurasians.
Here is a plot for the 1000 Genomes populations.
One thing I immediately noticed is that Peruvians have the highest frequency of the A allele in the dataset. Peru has had the highest COVID-19 death rate in the world, and its frequency of A means that a great number of people will be AA (the frequency of A squared).
I looked in Anders Bergstrom’s HGDP whole-genome data and found an interesting pattern in the frequencies of the G alelle:
Population
Freq
Count
2N
Karitiana
0
0
22
Pima
0
0
26
Surui
0
0
16
Yakut
0
0
50
Maya
0.04762
2
42
Oroqen
0.1111
2
18
Tujia
0.1111
2
18
Peruvian
0.1118
19
170
She
0.15
3
20
Cambodian
0.1667
3
18
Three of the four populations with no copies of the protective G allele are indigenous to the Americas. The Maya, who are known to have European admixture, also have very low frequencies of the G allele. Now, it is true that East Asians also have low frequencies of the G allele (the Yakuts also lack it, so perhaps this was ancestral to Siberians?), but they may have other protective variants (or, suffered through an earlier coronavirus epidemic). I think OAS1 may turn out to be one of the loci that could be associated with a higher risk to severe COVD-19 in the New World.
Some of the reaction to the finding that Etruscans were not genetically from Romans (Latins) despite being culturally quite different perplexes me. To review, Etruscans clearly spoke a non-Indo-European language and probably were the late-stage development of indigenous Mediterranean farming societies that date back to the early Neolithic. I said this in my Substack piece from March. Yes, I was going off a few samples, but the last ten years have taught us that usually (though not always) a few samples are sufficient.
We have precedence for Indo-European (“steppe”) gene flow does not always lead to cultural transformation. The Basques have mostly Indo-European Y chromosomes, and a lot of steppe ancestry, but retain their non-Indo-European language. Why? Well, one hypothesis is that the Basques were matrilineal (reported by some ancient sources), so Indo-European men assimilated to the clans into which they married.
But we don’t need a detailed or specific explanation. We just need to consider that genes and “memes” flow and transmit differently. Imagine a stylized model where large numbers of Indo-Europeans from Central Europe, with ultimate steppe ancestry, move into the Italian peninsula after 2000 BC. In most cases, they triggered language-shift as they overwhelmed native Neolithic societies. But in Etruria, or what became Etruria, they did not. Even if these Indo-Europeans didn’t invade Etruria, one can imagine a situation where continuous gene flow over the generations would reduce the differences between the two groups. It is quite possible, looking at the assimilation of Roman patrician clans with non-Latin origins (the Claudii were Sabines), that Indo-European speaking clans were assimilated into the proto-Etruscan confederacy and vice versa. You need extremely strong cultural barriers to prevent gene flow between groups.
Culture is not like this. Language and religion do not necessarily even pass down from parents, and it can definitely pass down asymmetrically. The Etruscan language could maintain its continuity in the face of gene flow every generation. There’s no mystery here.
The origin, development, and legacy of the enigmatic Etruscan civilization from the central region of the Italian peninsula known as Etruria have been debated for centuries. Here we report a genomic time transect of 82 individuals spanning almost two millennia (800 BCE to 1000 CE) across Etruria and southern Italy. During the Iron Age, we detect a component of Indo-European–associated steppe ancestry and the lack of recent Anatolian-related admixture among the putative non–Indo-European–speaking Etruscans. Despite comprising diverse individuals of central European, northern African, and Near Eastern ancestry, the local gene pool is largely maintained across the first millennium BCE. This drastically changes during the Roman Imperial period where we report an abrupt population-wide shift to ~50% admixture with eastern Mediterranean ancestry. Last, we identify northern European components appearing in central Italy during the Early Middle Ages, which thus formed the genetic landscape of present-day Italian populations.
The inference is basically what I concluded and stated this spring in my piece on ancient Rome:
By 1000 BC, on the eve of the Iron Age, a mixed ancestry derived from both Anatolian farmers and Indo-Europeans from the steppe was present all across continental Italy. Only on isolated islands such as Sardinia was the situation different, where Anatolian farmer societies continued unperturbed by Indo-European migrants, giving rise to the Nuragic civilization, with its massive fortifications. All the length of the Italian mainland, the ancestors of the Etruscans, Sabines, and Romans shared roughly the same genetic heritage, despite their ethno-linguistic differences.
The big novel find is that there is nontrivial Germanic ancestral shift after the fall of Rome. Some commenters have suggested this is actually just from rural Italians, who flooded back into the towns. This could probably be tested.
The traditional model, which I’ve alluded to before on this weblog before, is that Japan is a synthesis of Jomon and Yayoi, with the latter dominant, and bringing rice-agriculture to the islands. A new paper in Science indicates it may be more complicated than that.
Prehistoric Japan underwent rapid transformations in the past 3000 years, first from foraging to wet rice farming and then to state formation. A long-standing hypothesis posits that mainland Japanese populations derive dual ancestry from indigenous Jomon hunter-gatherer-fishers and succeeding Yayoi farmers. However, the genomic impact of agricultural migration and subsequent sociocultural changes remains unclear. We report 12 ancient Japanese genomes from pre- and postfarming periods. Our analysis finds that the Jomon maintained a small effective population size of ~1000 over several millennia, with a deep divergence from continental populations dated to 20,000 to 15,000 years ago, a period that saw the insularization of Japan through rising sea levels. Rice cultivation was introduced by people with Northeast Asian ancestry. Unexpectedly, we identify a later influx of East Asian ancestry during the imperial Kofun period. These three ancestral components continue to characterize present-day populations, supporting a tripartite model of Japanese genomic origins.
The Kofun period begins around 300 AD. The implication here is that there was a mass migration from the Asian continent less than 2,000 years ago, likely from Korea. The first agriculturalists, the Yayoi, seem to be a mix of native Jomon and individuals with strong affinities to populations in Manchuria.
Here’s a stylized representation that captures the turnover:
The Jomon are interesting because these results indicate low effective population, and, deep connections with ANE (Ancient North Eurasians). They also seem a clade deep within Northeast Asians, dating to the Pleistocene.
In any case, the authors admit that their sampling of the Yayoi is weak, so there needs to be follow-up here. If it does turn out that the Japanese are mostly Kofun-period, then I think that recalibrates our sense of its history a great deal. The Japan of the 7th century which enters into history was a very young nation.
The Indo-European horse sacrifice is a pretty widespread thing. Please note the table above and its shared characteristics. Notice the references to the chariots. Chariots were clearly invented by the Sintashta. And, it seems the horses that could pull them were a special breed, the ancestors of modern domestic horses. But putatively Indo-European people expanded in Europe long before the emergence of the Sintashta in 2200-2100 BC. For example, the Bell Beakers show up in Ireland ~2500 BC. Steppe ancestry shows up ~2300 BC in Greece. Therefore, the spread of chariot-culture, and the modern horse lineages, post-date Europe’s original Indo-Europeanization.
I think this indicates that the influence of the Iranian Scythians was felt all over the Indo-European zone…
Matt pointed me to the fact that the paper that’s going to come out:
Horse domestication fundamentally transformed long-range mobility and warfare. However, modern domesticates do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia ~3,500 BCE (Before Common Era). Other long-standing candidate regions for horse domestication, such as Iberia and Anatolia, were also recently challenged. Therefore, the genetic, geographic and temporal origins of modern domestic horses remained unknown. Here, we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they rapidly expanded across Eurasia from ~2,000 BCE, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioral adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe ~3,000 BCE driving the spread of Indo-European languages. This contrasts with the situation in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BCE Sintashta culture.
If you have an interest in the domestic horse (I have) you are aware it’s the product of massive demographic radiation from a small founder population. With ancient DNA we now know where it started: with the Sintashta people of the Volga to the Ural steppe 4,000 years ago.
This is not totally surprising, because we know that the Sintashta were highly warlike and they invented the light war-chariot. This technology spread across the whole Old World, from Egypt to China to Ireland. In some cases, I believe that this was mediated directly by the Sintashta, the early Indo-Iranians. Not only were the Mitanni elite of Syria 3,500 years ago speaking an Indo-Aryan/Iranian language, and worshipping Indo-Aryan/Iranian gods but genetically some of them retained their steppe character. The Sintashta also had domestic dogs, but the lineage of these dogs persists only in China today. Not coincidentally, light war-chariots that are clearly copied from the Iranian-style vehicles show up in Shang China in 1200 BC.
The genetic/demographic impact won’t be visible in many areas. Perhaps Indo-Iranian mercenaries arrived in a city-state, and eventually taught the natives how to build, maintain, and utilize war chariots? This seems plausible. To this day we aren’t quite sure where the wagon was invented because it spread almost immediately over much of Western Eurasia 5,500 years ago.
We also have to remember that the “Iranian” zone of domination was far wider in antiquity than in the present. Around 500 BC Scythians were present as far east as Mongolia, as far west as Hungary, and as far south as northern Iran itself. This means that they could easily have spread the chariot within their own cultural-zone and then it was rapidly adopted by adjacent groups to the east, west, and south.
Over on Twitter the eminent population geneticist Molly Przeworski has an important and lauded thread up:
The thread has been widely re-tweeted and quote-tweeted by biologists. This prompted a response by a prominent sociologist, who quoted this from Kathryn Paige Harden’s discussion with Sam Harris: What Harden is alluding to is that heritability within populations is not portable necessarily to between populations. In less sophisticated hands, this is almost used as an incantation. In my review of Harden’s book I said the following:
The biological reason that this extrapolation founders is that human populations differ, and those differences matter. The genetic architecture of intelligence may vary between populations so that predictions from the markers in one population are poorly predictive of variation in another, in line with the general concerns for GWAS portability…Harden points out correctly that population structure exhibits different layers of granularity and continuity. Perhaps a prediction trained on British samples is poorly predictive in Pakistanis. But what about Iranians? If it is poorly predictive in Iranians, what about in Bulgarians? The ability to infer within and between-group heritability is conditional on what you mean by “group,” and that is to some extent a subjective choice guided more by heuristics and instrumental utility than idealistic differences between races.
To be entirely frank I think Harden was on solid ground as a behavior geneticist with psychological training who relied on what population geneticists say publicly all the time about heritability and group differences. The issue is that I do not believe population geneticists were entirely candid about the deep texture of their assumptions, beliefs, and expectations. They wanted to be left alone to do their research, and so relied on a mantra to make people leave them alone, and now that mantra taken so literally is coming back to haunt them. One reason Prezworski’s thread got a lot of attention is privately this is the sort of intuition and sense that’s widely understood, but the issues are subtle, so to outsiders people just leave it off with the quick quips about portability. A friend told me “Molly doing this is like a goddess descending to Earth to speak to mere mortals so it will get a lot of attention.”
The real issue though is that some are now rather perturbed that Harden and behavior geneticists are trying to shield their study of psychological trait heritability from charges of racism by separating the discussion of between and within-group differences by implicitly reifying “population.” Additionally, some geneticists are quite unhappy at the discussion of heritability when it comes to psychological characteristics, so what was a convenient mantra to have people leave them alone is now coming back to haunt them, as it’s opening up avenues for research that they’re not comfortable with, are not interesting in, and believe are possibly dangerous. To be candid if I was Harden I’d be a bit peeved since all she’s doing is repeating what a lot of authorities in the field have been writing and saying for decades.
Nevertheless, if you take a look at the people who re-tweeted and commented on Przeworski’s thread it’s pretty much everyone. The high and mighty, all the way to the low. It was positively re-tweeted by people who are very skeptical of the study of heritability in psychological characteristics in humans (to be charitable). And, it was positively re-tweeted by me. Since so many people liked it and re-tweeted it, I can tell you it was re-tweeted by people who are actually quite open to and interested in the study of psychological characteristics in humans, within and between groups, without divulging confidence (I checked who commented and re-tweeted and liked).
So what’s going on? Prezworski’s group has published several papers in this area (for example, The evolution of group differences in changing environments), and one of the upshots for many is that there’s a lot less certainty about the heritability of many traits and its utility for polygenic risk scores even within groups because of uncorrected confounds. Some people took from this that polygenic risk scores are useless (not necessarily Prezworski and her group!). But when I talked about these findings with Amit Khera, who works on polygenic risk scores relating to cardiovascular disease, he was actually happy about these results. Why? Because he wanted to correct any confounds there were. He viewed these results not as a death knell for polygenic risk scores, but as a way to make them better, more accurate, more precise. He’s a medical doctor who is trying to help people in their health decisions. All he cares about is greater effectiveness. He’s not invested in a particular result, he’s invested in outcomes (OK, at least ideally, but I talked to him and his enthusiasm seemed genuine).
This is almost certainly why people who think polygenic risk scores are useful, and heritability in psychological characteristics are real, and vary widely in human populations, re-tweeted the Prezworski explainer. I myself did for this reason. My own current belief is there’s good evidence for heritability for a lot of behavioral traits, and that polygenic risk scores can be useful, at least on the margin. But we need to get better, and to do that, we need to explore all the subtle distinctions and details in relation to environmental and genetic variation. This is no guarantee. Perhaps the skeptics of polygenic risk scores will be correct (I doubt it, but who knows). But we’re not at the point where we can settle that question right now. More science needs to be done.
Finally, we need to address the magic of genes. People put a lot of stock in genes for various ideological reasons. But the reality is a lot of environmental factors taken for granted by many (e.g., shared home environment) are a lot less clear and well understood than genes are. And yet the skeptical takes don’t rain down on social science inferences and correlations. Mostly because they’re not seen as insidious because they’re environmental. But causes are causes. When there is a great deal of environmental variation in an outcome that doesn’t mean that you can control it, or you even know what it is. A lot of what is in the “E” in the ACE model is mysterious. Many focus on genes because they’re clear and distinct.
Obviously, I’ve had less time for this weblog due to other things, like my Substack. Please check out Among Afghans: jewel of the dragon if you haven’t. I post correspondence from a reader here there at the end, so it will be familiar.
Also, my mid-month link round-up is up over at Substack. Please check that out!
I don’t know if I mentioned this elsewhere, but I’m a paying subscriber of FdB. Mostly because I want him to be paid to write stuff like this and this. Most Left-liberals outside of genetics aren’t aware of the decreasing cost of sequencing plot from the NIH, or the existence of companies like Genomic Prediction and Orchid. Freddie is woke to all that. He’s an irascible character; I had my run-ins with him when he decided to send me unsolicited emails telling me what he thinks about me (mixed reviews). But I’ve come to the conclusion only the irascible can really speak the truth at this point. So here we are.
Unless you’ve been asleep, you’ve seen Can Progressives Be Convinced That Genetics Matters?, which is a pretty hagiographic profile of Dr. Kathryn Paige Harden in The New Yorker. This is from the same writer who wrote a hit-piece against David Reich. Is it something in journalism that they can only write hit-pieces or hagiographies? Is this demand side?
Two observations:
– The warm-glow of The New Yorker seems to be allowing the left/mainstream press to approach Harden’s ideas fairly instead of dismissing or demonizing
– A lot of scientists really dislike the profile and there’s been a lot of blowback. This, in contrast to the “circle the wagons” reaction around David Reich more or less. I think this is due to the fact that scientists would prefer more neutrality and a mixed portrait. They thought the profile of Reich was one-sided, and they think the profile of Harden is also one-sided. To be frank, I support both Reich and Harden’s projects.
There are some digs at Reich in Harden’s book, The Genetic Lottery. I actually sent the chapter in question to some human population geneticists to make sure my reaction wasn’t too biased (yes, I’m biased, I admire Reich a lot as a scientist and a human), and they told me I wasn’t crazy. So I have some defense of Reich in my full review of the Harden book (this didn’t make the final cut at UnHerd).
As for Harden’s project, I’m on the more pessimistic side because on social media scientists are connecting it to racism. Whether she’s correct or not if that sticks the project is obviously over. It’s a word of power, and will sink the project before it launches.
The Other Afghan Women. This is basically a story that explains how the rural Afghans viewed the American occupation and intervention, and all the horror we generated. This was published in 2021, but really it could have been published as early as 2001. From what I’ve heard American forces caused a lot of “collateral damage.” In the early years, the press was sympathetic, so they never reported on that. And, the US military has clamped down on leaking too much about the atrocities. When I was in grad school I randomly had beers with some construction workers at UC Davis. One of the guys went into a mental fugue and told us that he shot a dozen Iraqi prisoners in the head after one of his buddies got blown up by an IED. He kind of apologized for freaking us out, and explained: “you all don’t know anything about what’s going on, they cover it up when they can.” Others have told me the same, though they haven’t copped to war crimes.
We have identified at least five pulses of human dispersal into northern Arabia, each associated with a phase of decreased aridity. The differences in material culture between these phases—with two phases of Acheulean technology and then three distinct forms of Middle Palaeolithic—suggests that diverse hominin populations, and probably even species, were expanding into the region at different times…
Little is known of the Pleistocene fauna of southern and eastern Arabia, but the repeatedly distinctive, localised, character of material culture suggests that crossing the Red Sea at the Bab al Mandeb was not a primarily dispersal route and that instead populations filtered through northern Arabia. In northern Arabia the growing fossil record suggests repeated connections to Africa across a contiguous grassland zone through the southern Levant which formed during repeated humid episodes (discussed in SI 10). To that we can add significant aspects of material culture which we have reported in this paper. The absence of Acheulo-Yabrudian assemblages in northern Arabia, and the southern Levant, suggests that the Late Acheulean in this area relates more to Africa than to areas to the north. Likewise, with the early Middle Palaeolithic at KAM-4 (Assemblage C of the Northwest Lake) both technological features (such as the methods of Levallois surface preparation, see SI 7) and quantitative characteristics in terms of PCA of Levallois flake shape situate the assemblage between the Levantine Early Middle Palaeolithic the early Middle Stone Age in East Africa (SI 9)…
…The possible MIS 3 presence of Neanderthals in Arabia may suggest that they expanded further south than previously thought, and highlights that there is currently little clarity on where the main pulse of admixture between Homo sapiens and Neanderthals occurred, beyond probably Southwest Asia broadly.
As a closing note, we emphasise that as well as our results being consistent with repeated pulses of hominin dispersal out of Africa into Southwest Asia, the possibility of movement in the reverse direction should be kept in mind. Given factors such as current uncertainty on the background to the earliest known Homo sapiens in Africae, and discussions on the possible involvement of a hominin closely related to Homo antecessor as an ancestor of our species, currently only known from Eurasia, as a precursor to Homo sapiens, building reliable records for the later Quaternary in Southwest Asia is not only important for understanding ‘out of Africa’ dispersals, but also for ‘into Africa’ dispersals.
