Problems in PRS?

Variable prediction accuracy of polygenic scores within an ancestry group:

Fields as diverse as human genetics and sociology are increasingly using polygenic scores based on genome-wide association studies (GWAS) for phenotypic prediction. However, recent work has shown that polygenic scores have limited portability across groups of different genetic ancestries, restricting the contexts in which they can be used reliably and potentially creating serious inequities in future clinical applications. Using the UK Biobank data, we demonstrate that even within a single ancestry group, the prediction accuracy of polygenic scores depends on characteristics such as the age or sex composition of the individuals in which the GWAS and the prediction were conducted, and on the GWAS study design. Our findings highlight both the complexities of interpreting polygenic scores and underappreciated obstacles to their broad use.

For my podcast, I recently talked to the first author of Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. He turned out to be pretty sanguine about this result. We’re in the early years of the polygenic risk scores. There’s going to be a lot to learn…

Genetic correlation between friends

There is an interesting, and sexy, line of research which suggests that people who are non-related friends are genetically more similar than you’d expect. For years people have been telling me privately that this is not likely to be robust, and probably just really really subtle structure (friends of mine). But most of these were private gripes. Now a group has written a preprint outlining the basis from skepticism, No evidence for social genetic effects or genetic similarity among friends beyond that due to population stratification: a reappraisal of Domingue et al (2018):

Using data from 5,500 adolescents from the National Longitudinal Study of Adolescent to Adult Health, Domingue et al. (2018) claimed to show that friends are genetically more similar to one another than randomly selected peers, beyond the confounding effects of population stratification by ancestry. The authors also claimed to show ‘social-genetic’ effects, whereby individuals’ educational attainment (EA) is influenced by their friends’ genes. Neither claim is justified by the data. Mathematically we show that 1) although similarity at causal variants is expected under assortment, the genome-wide relationship between friends (and similarly between mates) is extremely small (an effect that could be explained by subtle population stratification) and 2) significant association between individuals’ EA and their friends’ polygenic score for EA is expected under homophily with no socio-genetic effects.

From shades of gray fantasy to woke fantasy

Vox has an interesting but predictable reaction to the finale of the show that much of America was watching, The Game of Thrones finale had a chance to break the wheel. It upheld the status quo. The show is obviously now its own thing apart from the books. But as someone who was reasonably immersed in George R. R. Martin’s original heterodox vision, it strikes me that the author of the Vox piece misunderstands (consciously?) the nature of the author’s transgressions (albeit, probably profitably for clicks):

Game of Thrones was initially built on a premise of subverting established high fantasy tropes, and surely one of the most innate fantasy tropes of all involves the idea that only men are fit to rule

Perhaps the television show is different but the above makes no sense in light of the thrust of what Martin was depicting and how he transformed the relatively stale high fantasy genre.  Before A Song of Ice and Fire , the most prominent epic high fantasy of the late 20th-century was clearly Robert Jordan’s The Wheel of Time (with perhaps an honorable mention to Terry Brooks’ highly derivative and mediocre body of work). Martin has admitted his debt to Jordan, but on the whole, I think the only way in which the latter matched the former would be in the grandness of vision. Martin’s world-building is superior, and Jordan confessed that every primary female character in the novels was somehow based on his wife (who, I presume, really enjoys standing with her hands on her hips and tugging her braids).

The Wheel of Time is a great series if you are a 13-year old boy, with the requisite amount of maturity and complexity to satisfy the early adolescent imagination. Though there is brutality galore implied in the world that Jordan creates, evil is drawn in more antiseptic terms than in Martin’s world, where someone like Ramsay Snow becomes the living embodiment of fecal cruelty upon the earth. In an email exchange with Martin 1999, he confirmed to me that he quite enjoyed Bernard Cornwell’s Warlord Chronicles, a Dark Age Arthurian historical novel which was vivid and unflinching in its description of brutality.

One aspect of Martin’s subversion of high fantasy tropes was tearing away the adolescent catering facade of a world of bright honor and chivalry pitted against pure evil. As Martin’s novels proceed the peeling away of the mask reveals a world regressive and cruel, where hope strives against the darkness in humanity. The medieval secondary world settings sometimes intersect with a darker and more exotic sensibility. Daenerys Targaryen’s explorations in the novels are redolent of 1970s DAW paperbacks, such as The Birthgrave, which are set amongst fallen civilizations where barbarians prowl ruined landscapes.*

What the author of the Vox piece echoes is a desire for the unjust premodern world to be as just as our own, in a manner that comports with the progressive sensibilities of 2019. That would certainly make it relatable, and easy for people to identify with. But this is literally the opposite of the way in which Martin was subverting the tropes, showing how brutal knights could be, how amoral political leaders were as a matter of course, and how false romantic histories often end up being when you understand the reality undergirding the myth-making. The more antiseptic fantasies which preceded his novels were easier for the core audience to take in, not harder.

A Song of Ice and Fire is a series which leverages the superstructure and set of expectations from formulaic high fantasy geared toward adolescents who want bright lines, flat characters, and role-playing game plots, and stuffs it full of the verisimilitude of realistic historical fantasy.** This means that though Martin can make a nod toward modern sensibility in character development and depth (e.g., both Sansa and Arya in the novels appeal to early 21st-century expectations of what a young woman in difficult circumstances can achieve with focus and determination), the framing social backdrop is often even more regressive and anti-modern than more imaginative and thinly drawn works.

Martin’s “smallfolk” are treated more badly because the ruling elite is just as selfish and cruel as they were in our own world.

Fantasy is a conservative genre. I wrote about this in Can We Make Tolkien “Woke”? (and got a positive comment from fantasist R Scott Bakker, whose own brutal series probably got some oxygen due to A Song of Ice and Fire).

But, if this makes you unsatisfied, I have a solution: science fiction. If you want to read speculative fiction of ideas which bend your mind and expectations and align with progressive and post-progressive sympathies, then everything is there for you. Just look. The Left Hand of Darkness was written in 1969! And it is entirely readable in a satisfying way in 2019.

You can’t rewrite the past to make it more palatable to the present unless you’re a political ideologue. But the future presents many more speculative opportunities.

Addendum: The anti-slaving passions of Daenerys in the books always struck me as one of the more unrealistic aspects of Martin’s plot elements, since slave revolts in the ancient world always focused on freeing the slaves themselves, not abolishing slavery. But A Song of Ice and Fire is a fantasy, so he’s allowed some liberties.

* Martin is a huge fan of Jack Vance’s Dying Earth. The landscape of Essos in the wake of the collapse of the Valyrian Freehold and its imperial domains has a lot of similarities to fantasy and science fantasy set in these decadent and decrepit civilizations. Also, there are some similarities between the “protagonist” in  The Birthgrave and Daenerys Targaryen that are striking to me. To name three, their physical appearance, the “white savior” motif, and incest.

** Brandon Sanderson extends the spirit of this sort of “boy scout” fantasy in novel directions in his work. It can be done better than it was, and Sanderson shows exactly how.

The end of the universal Western civilization

During a conversation with Carl Zha (already posted for BrownCast patrons) I inquired about Chinese views of the rest of the world and China’s relationship to other nation-states. I reflected offhand in some ways we don’t know how to deal with this “multi-polar” world, where Asian powers are again relevant after many centuries of being in the shadow of Europe and its offspring. Some of this is also reflected in India, where a rising reactionary conservative nationalism is the odds on favorite to retain power when the tallies are counted for the 2019 election.*

If I live my expected lifespan, I will see the end of the long centuries of the hegemony of Greater Europe. Today the European Union and the USA make up about 30% of the world’s GDP. India and China together are 25%. In 2050 the EU and USA will be 20%. India and China will be 35%. Many projections put Asia as a whole at (excluding the Middle East) at 50% of the world economy in 2050.

If Asian societies maintain current economic momentum, they will have returned to the same proportion of the world economy as they were in ~1800. This date intuitively makes sense. Though the British, under the East India company, were already advancing their way through the subcontinent, in 1800 Manchu ruled Imperial China still retained certain self-confidence, born of a century of economic and demographic expansion.

The 1793 Macartney Embassy saw the Chinese treat the British as they always had. But by this point the dynamic force of history had moved past the Chinese, they just didn’t know it.

The oldest person I have known personally with any great familiarity was my maternal grandfather. He was born in 1896 and died in 1996. It is unlikely that he knew anyone personally who remembered a time before the hegemony of Europeans across the globe. But, it is entirely possible his own grandfather, my own great-great-grandfather, knew people for whom the British as an eternal and dominant force of history was something of a novelty in their youth. My own children will live on after me, likely into the 22nd century. Most of their lives will play out in a very different epoch when it comes to the balance of civilizations.

Of course, one can argue, with some reason, that all civilization from here on out is Western civilization. But I think we need to think back to the late 1990s, and what we believed at the time a post-Western universal civilization would look like. There was an optimism that the end of history would force nations like China to open up politically, while India would match its democratic humanism with robust economic growth. Boris Yeltsin’s Russia was the sometimes helpmate, and sometimes supplicant, of the USA. Though people in India might speak Hindi and eat off thali, while those in China would speak Mandarin and eat with chopsticks, by the end of the 21st century many expected that universal values would lead to a natural federative political state on planet earth. There was no need for top-down world government when capitalism and democratic liberalism spread to all the nation-states on the planet.

Though we should be cautious of swinging in the opposite direction, it does look like the 21st-century will exhibit its own characteristics, not just reflect the dreams of the late 20th.

* I say reactionary because I don’t think Hindu nationalism, like Islamism, is comprehensible without the shock of European modernity. Though these movements present themselves as primal and authentic, they’re really syntheses that came out of the dialectic between the native (Indian) and the colonial (European).

The myth of the primitive Arab culture

The author of The Map of Knowledge freely admits that her education was in Classics, so it was remiss in “non-Western” history. These gaps show up in the text of her book. For example:

It helped that Sassanian culture was one of the most sophisticated and impressive on earth, and that Arab culture was young and relatively primitive. Just a few generations earlier, Muhammad’s people had been Bedouins, wandering the deserts of Arabia….

This seems plausible and uncontroversial to most people at first glance. Even more so to those who read their Ferdowsi. The problem is that even minimal reflection will indicate that this is just not true.

I have an advantage because last week I was on a podcast with a scholar of pre-Islamic Arabian literary culture (it’s already on the patreon page for patrons), so many facts are fresh in my mind. The fact is that the Arabs tribes were liminal to Romans and Persians for many centuries, and exhibited various degrees of integration with these larger civilizations.

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The long now library?

Violet Moller’s The Map of Knowledge: A Thousand-Year History of How Classical Ideas Were Lost and Found is written for a non-academic audience, and relays the story of how Classical knowledge was passed down to the West, which eventually leads to the Renaissance. This is a well-known story, and iut is written engagingly (at least so far). I do get a sense that the author writes intending to suggest the importance of a liberal open society to the public. But these moral lessons can be ignored if you are aware.

For a work attempting to resurrect the importance of non-European societies, in particular, that of the Islamic civilization, it is to this point strangely Eurocentric, in particular, Western European centric. The importance of Al-Andalus is particularly important, from what I recall, to the intellectuals of Paris and Oxford, who are the forebears in many ways of the Anglo intellectual tradition. In contrast, Italians were just as much influenced by the emigration of Byzantine scholars west to the peninsula during the medieval period. And though the Muslim societies did an excel at transmitting the philosophy of the ancient world, it is to the Byzantines that we owe the humanistic worlds. The great Greek playwrights would be names in encyclopedias without the efforts of men such as Constantine VII.

If you want to read a book that covers the lacunae in The Map of Knowledge, I’d suggest Sailing to Byzantium, which is also written at a popular level. Additionally, the end point of the book is the efflorescence of Western Europe. But it might be interesting to write a book at some point how Galenic medical philosophy became a basis for Tibetan traditional medicine! (a fact mentioned in The Map of Knowledge)

All that being said, one of the points brought home in this book is the importance of institutions in copying and maintaining knowledge. Aside from exceptional conditions (e.g., papyrus in the Egyptian desert!), ancient texts simply will not survive into the present. It turns out that this sort of information is actually less robust than DNA. Papyrus scrolls, parchment, and paper, all have half-lives on the order of a century or so. Our current digital formats are even more tenuous. Though I’m not necessarily an alarmist, is it that unlikely that in the next few thousand years technological civilization won’t go through a major shock and regression?

Then what? What if there are no physical books around, and the electronic cloud disappears? What I propose is a massive Rosetta Stone project to make copies of books in hyper-durable materials, translated into hundreds of languages, and deposited in safe caches all across the world. A literary version of the Millennium Seed Bank Project.

The rise of the steppe (on PBS)

David Anthony’s The Horse, the Wheel, and Language: How Bronze-Age Riders from the Eurasian Steppes Shaped the Modern World is a bit dated, but it’s still a useful read. Papers such as Population genomics of Bronze Age Eurasia and Massive migration from the steppe was a source for Indo-European languages in Europe come out of the tradition that Anthony comes out of. Arguably these thinkers even underestimated the demographic impact of the people from the steppe.

If you are interested in this topic, I think you might find First Horse Warriors: The advent of horse riding changed the course of human history and the genetic makeup of humankind, worth a watch. I think the second half, in particular, will be interesting. Researchers whose names you see only in papers are interviewed. So if you want to put a face to the name, this is your chance.

I would say though that again watching this episode reinforces my point that visual medium is very low density in the information. They had to focus on a few major results and scaffold their visuals around that.

The main issue in the documentary is that researchers still debate the nature of the usage of the horse on the steppe. Anthony and Dorcas Brown have been arguing for an early date of widespread horse domestication, at least as early as 3500 BC. But others suggested a date closer to 2000 BC, around when the light war chariot was invented.

Religion and science, a foggy battlefield

One of the similar responses from very different camps to my National Review piece on evolution was that I was wrong to assert evolutionary biology doesn’t have atheistic implications. This perspective came from both some religious evolution skeptics and from atheists who agree with Jerry Coyne and Richard Dawkins.

My own view on this isn’t exactly subtle, but, it’s kind of muddled and has a few moving parts.

First, I am an atheist and have been self-conscious as an atheist since I was eight. Before the age of eight, I didn’t identify as an atheist, but with hindsight, it is clear to me that my views on God were primitive to nonexistent. I may have averred to you that I was a believer in Allah, but compared to the vast majority of people who would say such a thing Allah was not real to me as a person who really operates in this universe. Allah was an abstraction. And one of little deep interest to me.

Therefore,  I can say that my understanding of evolution has no implication for my atheism in its origin because I was an atheist long before I understood evolution. That’s just an empirical fact. It is also an empirical fact that there are a reasonable number of evolutionary biologists who hold various religious viewpoints. To my knowledge, there are no Protestant fundamentalist evolutionary biologists, as that’s a logical contradiction, but there are very diverse viewpoints excluding this.

These people are real, and I can’t deny their existence. Just as my atheism predated my understanding of evolution, their understanding of evolution did not necessarily result in a diminishment of their religion (though perhaps it modified it in some way).

Of course, these people could be logically wrong. And I think that’s what the religious evolution skeptics and fundamentalists of various sorts agree on. There are several issues with this. I think it misunderstands what religion as a phenomenon is: it’s not about a logical set of propositions. Even Aquinas’ effort is not airtight, and many are not convinced by Alvin Plantinga’s modern attempts utilizing modal logic. Religion is vague and amorphous enough as a phenomenon that I think it will always slip away from any formal refutation.

I am not here proposing ‘non-overlapping magisteria’. There are plenty of ways in which religion seems to intrude into domains of science or domains which can be scientifically informed. It’s just that religion is not a clear and distinct entity. And to be frank neither is science. Just as religion is often falsely reduced to a creed, so science is falsely reduced to a method. I do not believe there is an ‘out-of-the-box’ method that determines science. Rather, it is an outlook, sensibility, and culture, which iteratively attempts to explore patterns in the world around us and explain them.

Personally, I do think the scientific sensibility does lean one to a position of being skeptical of religious explanations. But this is more an intuition rather than a deduction. I don’t think science ‘disproves’ religion any more than religion ‘disproves’ science.

In the piece above I wanted to set aside my own personal views, which are tentative and inchoate, and simply observe that many scientists disagree with them in relation to their faith and their practice. The reality is that there are many great evolutionary biologists who are religious, and I have no issue with that. At this point in my life, I’m not too concerned that someone somewhere is wrong. I’d rather just learn things.

Note: I’ve been writing since 2002. I’ve probably held this sort of view since 2004 or so. I have probably written it before, but at this point, I guess I need to rewrite it. Also, I appreciate the “New Atheists” in their consistency, though I disagree with some of their assumptions about human psychology.

Open Thread, 05/12/2019

A History of Korea: From “Land of the Morning Calm” to States in Conflict is very cheap on Kindle right now. Seems less propagandistic (unwittingly to be fair) than some other Korean histories I’ve read. Basically, Korean histories seem less interesting in detaching from nationalism as they’re writing, and it can get grating (everyone has opinions, but you don’t want them leaking through all the time).

If you haven’t, you might want to check out my podcast interview with an epigeneticists who takes a dim view of some of the hype in the field. If you are a geneticist you’ll have all this before of course, whether you agree with it or not.

Harvard Drops Harvey Weinstein Lawyer as a Faculty Dean. A contrary take from Harvard students: ‘With Us or Against Us’: Current, Former Winthrop Affiliates Say Faculty Deans Created a Toxic Environment Stretching Back Years. Basically, some people who I know who were at Winthrop house are telling me that the administration took the move because the protests gave them the opportunity. It’s an interesting epistemological question here for all these ‘culture war’ conflicts. A lot of the time the underlying dynamics are more prosaic and personal than what you might read in the media, but it’s not in anyone’s interest to surface that.

Here’s reader survey as a .csv. No big surprises. Though some of you don’t want me to post about Game of Thrones. Well, that will a “done” thing soon anyhow. I doubt I’ll be blogging ten years from now when Martin comes out with the next book… (if…)

Evolution unleashed: Is evolutionary science due for a major overhaul – or is talk of ‘revolution’ misguided?. Kevin Laland. The usual response is “niche construction isn’t new.”

Evaluation of the Diagnostic Stability of the Early Autism Spectrum Disorder Phenotype in the General Population Starting at 12 Months.

Shadi Hamid is getting dragged on Twitter for working with a “Christian Zionist” organization (Shadi disputes the characterization). The weird thing is a lot of the critics are journalists who work for AJ+, which is a subsidiary of Al Jazeera Media Network, which is run by a royal family that rules a Salafi state, Qatar. There are good things and bad things about Qatar. But journalists who work for a techno-reactionary absolute monarchy should perhaps be careful about pointing fingers from their glass houses.

Asia Bibi: Pakistan’s notorious blasphemy case. The utilization of these laws to target minorities by people with personal disputes is really familiar, though the consequences are more extreme than what you would see in the West. A lot of the time the public is even tacitly aware of the personal nature of the original dispute, but they back the idea of blasphemy laws so much that innocence is no defense.

New podcast on anthropology and archaeology, The Arch and Anth Podcast.

Why falsificationism is false. Since I know a little philosophy of science I have known that Popper is passe within philosophy of science for a long time. But it is surprising to many scientists.

Is species a social construct? Some people have argued that rejecting the species concept by biologists is a deepity. The issue that biologists have is that the public has a different perception of what species are than what biologists have. The public perception derives from folk biology, augmented by stuff like the Bible (species = “kinds”). This drives biologists crazy.

5-HTTLPR: A POINTED REVIEW. Been hearing this from friends since 2007 or so.

Variable prediction accuracy of polygenic scores within an ancestry group. Important.

Pakistani Christian girls trafficked to China as brides. China’s demographic problems are going to leave a huge shadow over Asia.

Noah Carl’s response.

Comparing signals of natural selection between three Indigenous North American populations.

Don’t Let Students Run the University and Academe’s Extinction Event Failure, Whiskey, and Professional Collapse at the MLA.

Unraveling ancestry, kinship, and violence in a Late Neolithic mass grave. This week’s episode of The Insight will be with two of the corresponding authors of this paper.

Discovery of ongoing selective sweeps within Anopheles mosquito populations using deep learning. A podcast of The Insight in a few weeks will drop with the last author, Andy Kern. Though we talked about pop-gen and machine learning a lot, the last 15 minutes ended up about the issue of how pop-gen needs to reform itself in terms of large collaborations instead of small competing labs.

Why the Uyghurs as we didn’t know them didn’t exist until after 1000 AD

The period between 300 AD about 750 AD is sometimes termed the “Buddhist Age.” The reason for this is is that this was the period when Buddhism was established in China, and, was still a force in mainland South Asia. It is also when Buddhism was arguably the dominant religion in much of Central Asia. In fact, Buddhism probably arrived in China mostly through this route, via the city-states of the Tarim basin.

A point of interest for many in the public is that some of these Tarim basin Buddhists looked very “Western.” That is, they had European features and coloring. The reason for this is that their ancestors were the eastern edge of the Indo-European migrations on the steppe. Many of them famously spoke Tocharian languages, an extinct branch of the Indo-European languages. But others spoke Iranian languages. Iranian not in that they came from Iran, but that they were descended from proto-Iranians of the steppe.

A few years ago there was a discussion on this weblog and elsewhere about very recent admixture dates for the western and eastern admixture components in the Uyghurs. That is, after 1000 AD. This struck many as too recent. I think perhaps I have an answer for what happened.

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