Razib Khan One-stop-shopping for all of my content

August 3, 2018

What if everything that’s not a disease is polygenic?

Filed under: FOXP2,Human Evolution — Razib Khan @ 12:34 am

In the early 2000s FOXP2 was dubbed the “language gene”. It was a sexy story. Humans exhibited accelerated adaptive evolution on this locus in relation to our relatives. Additionally, vocally oriented lineages such as birds and whales were also subject to the same process.

But over the past five years or so I’ve heard a lot of skepticism of the early claims as more genomic datasets have come online. Cell has a new paper which pretty much smashes the door down and breaks the skepticism out into the open, No Evidence for Recent Selection at FOXP2 among Diverse Human Populations:

FOXP2, initially identified for its role in human speech, contains two nonsynonymous substitutions derived in the human lineage. Evidence for a recent selective sweep in Homo sapiens, however, is at odds with the presence of these substitutions in archaic hominins. Here, we comprehensively reanalyze FOXP2 in hundreds of globally distributed genomes to test for recent selection. We do not find evidence of recent positive or balancing selection at FOXP2. Instead, the original signal appears to have been due to sample composition. Our tests do identify an intronic region that is enriched for highly conserved sites that are polymorphic among humans, compatible with a loss of function in humans. This region is lowly expressed in relevant tissue types that were tested via RNA-seq in human prefrontal cortex and RT-PCR in immortalized human brain cells. Our results represent a substantial revision to the adaptive history of FOXP2, a gene regarded as vital to human evolution.

Basically, our confidence in the inferences ran ahead of the data on hand. The reason that the story of the “language gene” spread like wildfire is that people wanted to believe. It was obvious that we were special. And we wanted to find how we were special.

In the 2000s, and even today, there was an idea that some single mutation might have allowed for the “Great Leap Forward” into behavioral modernity. I think that that model is probably wrong, and modern humanity was a more gradual and stepwise development. During the Eemian interglacial from 130 to 115 thousand years ago, agriculture did not emerge. No “lost civilizations” to our knowledge. Something happened to our species over the last 100,000 years. Probably biological, though in a way that facilitates cultural plasticity and evolution.

But genetically I bet it wasn’t that “one thing.” It was a lot of different things.

August 2, 2018

Rakhigarhi sneak-peaks

Filed under: Genetics — Razib Khan @ 11:30 pm

Over at my other weblog, noting that the Indian press is finally starting to simply report the substantive contents of the Rakhigarhi results. As we all know the media can distort and misrepresent, so we need to be cautious and wait on the final paper, mostly because with that the authors can speak freely and without intermediation. But, I have heard through the grapevine the general results, and the results are exactly what Outlook India is currently reporting.

The Rakhigarhi samples themselves aren’t that interesting to me. But, Niraj Rai seems to be pushing the admixture event with IndoA-Aryans after 1500 BC. This could be a misquote, or, it could be that the researchers from various groups now have enough data to fine-tune their parameters so as to narrow down various admixture timing events.

DNA results from Rakhigarhi are now being reported (really!)

Filed under: Indian Genetics — Razib Khan @ 10:34 pm

It looks like Outlook India is the first out of the gates to start reporting on the results from Rakhigarhi in northwest India, We Are All Harrapans. This is a “mature phase” Harrapan site that dates to about 2250 BC or so. Media reports have always been garbled on this topic, so anything that is coming not out of a paper needs to be treated cautiously. But I’ve heard some of the same things from independent sources from a while back, so I believe that this reporting is broadly on the mark.

Basically, the individual(s) they got DNA out of did not have any Eurasian steppe ancestry. This seems to confirm again that Eurasian steppe ancestry, which is found in fractions as high as ~30% in twice-born varna in Northern India (e.g., Rajputs, Tiwari Brahmins), arrived after 2000 BC. That is, after the peak period of the Indus Valley Civilization.

Again, one has to be wary of anything from the media because I’ve heard so many confusing things, including claims of garbled quotes, but here’s one of the authors of the forthcoming paper being quoted:

We did some analysis to figure out the exact date of the admixture. We have prepared a model in which all these stats fit together very tightly and that model suggests the Central Asian admixture happened about 1500-1000 BC…. Significant mixing happened around 1000 BC, also at 800 BC and 600 BC.

This is totally in line with the results from the March preprint discussed in the piece. That is, the Swat Valley samples show admixture and genetic change after 1200 BC. And the semi-historical understanding that we have of India during the period between 1000 BC and the rise of Mauryas is that it was a society in flux. But the only way the dating was changed by the Rakhigarhi results is if the genome is high enough quality that it allowed them to narrow down the parameters on some of the estimates of admixture.

One thing to keep in mind is that it is unlikely that the “Harappan people” were one single people genetically. There was probably a lot of variation in admixture with the indigenous South Asian substrate. And, I believe that the inflated steppe & AASI (“Ancestral Ancestral South Indian”) ancestry you see in some North Indian Brahmin groups compared to Sindhis (who are more “Iranian”) is evidence that the Indo-Aryan intrusion resulted in an expansion of people with West Eurasian ancestry much deeper into South Asia than was the case with the Harappans.

And of the Harappans, some of the Indian scholars have asserted that their descendants are still present in the region. I think this is right, insofar as some of the jati groups, often scheduled caste, in the northwestern region of South Asia share a lot more affinity with populations to the south and east.

The “Islamic world” was not invented by Europeans

Filed under: History,Post-Colonialism — Razib Khan @ 2:46 pm

Aeon has published a piece, What is the Muslim world? Islamists and Western pundits speak of ‘the West’ and ‘the Muslim world’ but such tribalism is dangerous colonial propaganda. The piece itself is more subtle and textured than the headline and subhead. Unfortunately, I’m 99% sure that 90% of readers will simply take the headline at face value and not engage with the text of the piece.

That being said, I also strongly disagree with the overall message of the author’s piece. He has written a book, The Idea of the Muslim World: A Global Intellectual History, where he presumably extends the argument. By the message, I mean that I believe the author overemphasizes the contingent, necessary and sufficient role of European colonialism in the idea of an Islamic world.

Anyone who has read a history of the modern world, as I have, knows that it is essential to integrate into that understanding the rise of the West after 1500, and the supremacy of the West after 1800. To a great extent, modern history is Western history.

But the West did not create everything anew, and there were, and are, preexistent identities which predate the West as we commonly understand it. Anyone who reads Al-Biruni knows very well that scholars in Islamic societies had a sense of us vs. them. Al-Biruni could admit that Indian civilization was characterized by a high level of intellectual sophistication, while also asserting its differences and uniqueness in relation to the Islamic civilization which had emerged in the wake of the Arab conquests.

In the Aeon piece, the author points out that Pan-Africanism, Pan-Asianism, and Pan-Islamism, developed as reactions to European colonialism. The first thing is to observe that Pan-Islamism is a very different thing than the idea of the “Islamic world,” a set of societies delimited by a cluster of beliefs and practices. Pan-Islamism is a modern ideology, strongly influenced by the rise and domination of the West. As such, contemporary Islamic fundamentalism is a reaction to modernity. But Islamic fundamentalism draws on older traditions within Islam, for example, the thinking of Ibn Taymiyyah.

Additionally, like many post-colonial thinkers, the author in the piece collapses different movements together in a mishmash as if they were equivalent. Pan-Asianism and Pan-Africanism have no deep historical roots, but were and are geopolitical responses to European domination. In contrast, arguably the West can not be understood without integrating the rise of Islam. Pan-Islamism appeals to a genuine history of pre-modern unity, before its dissolution and decay. Pan-Africanism and Pan-Asianism have been relative failures in comparison to Hindu nationalism and Islamic fundamentalism because they were thin, artificial, and purely geographic, constructions. In contrast, Hindu nationalism and Islamic fundamentalism appeal to and extend from true commonalities that have deep resonances.

The theoretical foundation for understanding what Pan-Islamic identity is and its historical precursors is that it is a “meta-ethnic” identity. Islam, like most of the world religions, binds together people of disparate backgrounds. It does not collapse differences, and it does not impose homogeneity. Nor does it mean that every Muslim shall stand with every other Muslims against every non-Muslim. Rather, it simply gives people from diverse backgrounds who may not know each other an immediate common ethical and cultural currency, tenuous as that may be.

Modern political movements have to be understood as reactions to events and situations of the modern era. But those political movements were not created ex nihilo out of a cultural vacuum. It is surely correct that in most cases one cannot understand the modern without considering the colonial era, but it is also true in many cases that one can not understand the modern without understanding the deep history of many regions of the world which long predate the colonial area.

Ancient pigmentation pathways and modern genomics

Filed under: Forensics,Genetics,skin — Razib Khan @ 1:02 am
Piebald horses emerge out of common pigmentation pathways found in humans

Unlike most mammals humans are highly dependent on our sense of sight. This is due to the diurnal nature of many primates. Our ancestors foraged for bright fruit, and so we developed stereoscopic color vision. But eventually the human lineage left the forests of our ancestors, and ventured out to the savanna. We turned our eyes to other uses than detecting fruit, from hunting, to developing a keen eye for art.

Humans are pre-adapted toward color vision

It is not surprising then that humans have had a fixation on the color of our skin and the pelage of our domesticates. Skin is our largest organ, and our complexion is one of the best indicators of ill health.

Additionally, humans have utilized the skin as a canvas upon which to apply tattoos and other coloration so as to indicate group membership. And, as humans from very different geographic regions began to meet each other, any differences in pallor were salient indicators of difference and distinction. Whole people were defined by their color!

In the ancient Near East the Egyptians termed themselves red, while their neighbors to the south were black, and West Asians from the Levant were yellow. Greeks and Arabs distinguished between the ruddy peoples of the north, and the black and brown peoples to the south, with their own ethnicity often defined as being at some sort of equipoise.

Nubians were depicted accurately by the ancient Egyptians

And yet for such an important trait, the genetic elucidation of skin color, and pigmentation more generally, has evaded us until very recently. To be fair, the genetic elucidation of most traits in humans evaded us until the last decade or so, because we did not have genomic tools to explore the whole range of possible genetic sites.

In 2003 the evolutionary biologist Armand Leroi wrote in the afterword of his book Mutants that it was surprising that geneticists were still unclear about what underlay normal variation on the trait of human skin color. This passage was written at an opportune moment. In 2006 a review paper was published, A golden age of pigmentation genetics, which reflected the fact that much had changed since Leroi had written that passage just three years before.

Through analysis of British mixed-race pedigrees geneticists in the 1950s concluded that skin color was controlled by many genes, but that much of the variation was localized to only a few loci. That is, variation on a few genes had a large impact. This means that genomic methods pioneered in the 2000s were well placed to discover the genetic basis of the variation of the trait. If the impact of the mutation was large, then you didn’t need a large sample size to detect it.

75% of the variation in eye color in Europeans is due to one gene

And so they have. Today researchers now know that about half the variation in skin color across populations is due to variation on about ten or so genes. The other half is mostly distributed across the genome. Additionally, they know that the gene that is correlated with blue eye color also effects skin color. Similarly, the gene that causes much of the blondness in Northern Europe is also correlated with skin color. The pigmentation characteristics are usually correlated together. Skin, hair and eyes are all often controlled by the same set of genes.

Though East Asians and Europeans achieve light skin through different mutations, it is also the case that those mutations are found on an overlapping set of genes. Pigmentation pathways are highly conserved in human populations. The wheel is always reinvented in the same way. In fact, the same genes show up over and over across vertebrates.The genetic mutation that results in blonde hair causes the piebald pelage in horses. The mutations associated with red hair in humans are found in the gene that is important in mouse coat color. The gene responsible for much of the difference in pigmentation between Europeans and Africans also has a lightening effect in zebrafish.

There is a great to be done to understanding the genetic basis of many diseases and complex behavioral traits. But with pigmentation genomics has yielded incredible results, producing forensic applications with utility in a wide range of contexts. This is because tens of thousands of years have produced humans who come in all colors, but through simple fine-tuning of the pigmentation pathways which vertebrates had utilized for hundreds of millions of years.

Skin color is a complex topic with numerous historical and anthropological layers. But when it comes to genetics it’s actually surprisingly simple.

You can see your skin, but are you curious about what your genes say about your pigment? Check out Neanderthal by Insitome to learn more!

Ancient pigmentation pathways and modern genomics was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

July 31, 2018

Documentary on the arrival of R1a1a-Z93 to South Asia (scions of the all-father!)

Filed under: Humor — Razib Khan @ 12:17 am

July 30, 2018

Ancient India, archaeology, etc.

Filed under: ancient india,Prehistory — Razib Khan @ 11:43 pm

I think I have asked before, but I’m soliciting suggestions about a book on Indian prehistory, with a focus on the period between 10 and 2 thousand years ago. India: The Ancient Past: A History of the Indian Subcontinent from c. 7000 BCE to CE 1200 looks decent, but I don’t have an ability to evaluate this stuff.

The reason is pretty simple. I’ve been asked to write a book chapter on the genetics of India. The draft is written, and I think we’re 80-90% done with the genetic “big picture.” The real work is going to be in synthesizing with archaeology. To be entirely frank I’m not sure how open Indian archaeologists are going to be to the new genetics, which is not stopping at any time in the near future. So I think perhaps I should see what I can snap together myself.

Anyway, suggestions appreciated. Though keep in mind that I don’t know much archaeology and don’t care that much about ancient village plans….

Open Thread

Filed under: Open Thread — Razib Khan @ 11:00 pm

Please keep the other posts on topic. Use this for talking about whatever you want to talk about.

Bubba has the babies

Filed under: Culture,Fertility,GSS — Razib Khan @ 10:32 pm

Today Colin Woodward, author of American Nations: A History of the Eleven Rival Regional Cultures of North America, has an op-ed up, The Maps That Show That City vs. Country Is Not Our Political Fault Line: The key difference is among regional cultures tracing back to the nation’s colonization. Woodward’s thesis is basically that the modern shape of American cultural and political conflict has deep structural roots in American history. This is the same argument that David Hackett Fischer makes in Albion’s Seed: Four British Folkways in America, and Kevin Phillips more broadly about the Anglo-world in The Cousins’ Wars: Religion, Politics, Civil Warfare, And The Triumph Of Anglo-America. These perspectives are useful because there is a tendency in modern American discussion to reduce the sum totality of the dynamic to the white supremacist order, as opposed to the “rising tides of color.” There is an area where the cult-of-Pepe and the identity Left agree descriptively (they just flip the good guys and the bad guys).

There is some of this in the Ezra Klein Vox piece, White threat in a browning America. There are the whites. And there are the non-whites. And never the twain shall meet.

On a side note, Klein’s reliance on social psychological research about white racial anxiety being elicited by priming or information which makes non-whites salient should be critiqued more thoroughly. I suspect most of us find the argument intuitively believable, but the past five years of the replication crisis in psychology, where social psychology was ground-zero, should really make us put our guards up about evidentiary claims which support views we already have a bias toward accepting.

In any case, Klein cites research which shows that non-Hispanic whites are now less than 50% of the births in this country. Rather than arguing about the future of racial identification, I was curious about which whites were giving birth. The problem with raw average total fertility rates is that they mask underlying variance. For example, in Britain the majority of Jews are non-observant, but the majority of Jews under the age of five are from observant families. This is a function of the extremely low fertility of the non-observant majority, and the very high fertility of observant Jews in Britain.

The reason I bring this up is that the different subcultures of the United States have different fertility rates. David Hacket Fischer posits four major Anglo-American streams which date to before the Revolutionary War: New England Yankees, Tidewater and lowland Southerners, Scots-Irish highlanders, and the diverse polyglot Mid-Atlantic region, from Quakers to Dutch. Woodward and others have a somewhat different taxonomy, but the broad sketch aligns.

The curious fact is that up between the 1640s and 1840s New England Yankees were the most fecund of the American Anglo-cultures. The fertility of New England was such that the region began to colonize parts of the United States which had heretofore been dominated by other groups. The eastern half of Long Island was taken over by New Englanders, and they became prominent in New York’s merchant class (there was also a Yankee migration into the Canadian Atlantic provinces). New England farmers swept past the Dutch dominated lower Hudson Valley and overwhelmed the rest of upstate New York, creating a cultural fission that persisted up to the Civil War between the pro-Southern city of New York and the fiercely Republican upstate areas.

In contrast, the population growth rate in the South was depressed compared to the North. Much of this probably can be accounted for by endemic disease.

Things are different now.

The CDC has data on total births by race and ethnic identity by state. I pulled the data and plotted them. The correlation between the number of births and the number of people in the states by race and ethnicity were very high (0.98 and such). Also, I removed about the bottom five states in total population. The data are from ACS sample surveys, and it is pretty clear that small sample sizes are a problem in some of the cross-tabs/states.

In any case,

1) everyone seems to have lower fertility in California
2) Texas is good for whites and Hispanics in terms of having children
3) blacks have very high relative fertility in Florida

Yes, you can see Utah has elevated fertility. No surprise there. Here are the ten states in my data with the highest number of white births to their white population from top to bottom:


Here are the states with a relatively low number of white births to total white population (Connecticut has the lowest number of white births to white population):

Rhode Island
New Hampshire
New Jersey
New Mexico

California is expensive. Florida and Arizona are filled with old white people. Many of the rest are Yankee.

The General Social Survey allows me to look at white ethnicities. I wanted to look at the number of children of various white ethnicities. I limited the sample to Protestants and Catholics.

Here are the results:

In the early 20th century Nordicists like Madison Grant were worried about the fact that Southern and Eastern European ethnics were going to overwhelm the Nordic stock of this country. But take a look at Italian and Polish fertility. People in urban areas have fewer children, and presumably white ethnics who remained identified by their ancestral heritage are disproportionately urban. When the Irish are split up by religion, Catholics tend to be more childless, and also have a minority with large families. This is probably tracking the intense secularization of white Catholics over the last generation, but the persistence of a traditionalist minority. Protestant Irish, who are probably often Scots-Irish, are similar to the other British Americans.

Finally, the ideological differences are really striking but unsurprising:

Left-liberal dominance of cultural institutions such as the media and academia are essential in part because it allows them to generate defections from people raised conservative. They can’t maintain their numbers through “natural increase” alone.

We’ll see what 2050 is life. I hope to be alive. But I think we’ll all be surprised in some ways by some of the defections and realignments. Michael Dukakis won West Virginia in 1988.

Open Thread

Filed under: Open Thread — Razib Khan @ 9:14 pm

Please keep the other posts on topic. Use this for talking about whatever you want to talk about.

The HGDP in the post-ascertainment era

Filed under: HGDP,Human Population Genetics — Razib Khan @ 6:45 pm

In the 1990s there was a huge debate around the “Human Genome Diversity Project” (HGDP). By the HGDP I don’t mean what you probably know as the HGDP panel, but a more ambitious attempt to genotype tens of thousands of individuals across the world. In the end activists “won”, and the grand plans came to naught. If you want to read about it, The Human Genome Diversity Project: An Ethnography of Scientific Practice has a scholarly viewpoint, though you can also just ask someone who was involved with the human population genetics community in the 1990s (this not a large set of scholars).

Ultimately the HGDP became the samples from L. L. Cavalli-Sforza’s dataset which you read about in The History and Geography of Human Genes. This is what drives the HGDP Browser. It’s also the data set at the heart of papers like Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation. Here is the abstract:

Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation.

These SNPs though were ascertained on European populations. That is, the genetic variation tended to be genetic variation found in Europe. This is a problem, and one reason that the Human Origins Array was developed. The ascertainment problem was really obvious when researchers were looking at Khoisan genomes, and noticed how much variation they had that wasn’t being captured on SNP-arrays.

Today, we’ve finally moving beyond the era where ascertainment is so much of an issue. At the SMBE meeting earlier this month Anders Bergstrom presented results from the HGDP using whole-genome analysis. When you look at the whole genome, you obviate the problem with selecting a biased subset of the variation. You can look at all the variation, or vary the variation you want to look at.

Bergstrom & company will have a paper on the whole-genome analysis of the HGDP in the near future. I assume it will be somewhat like the 1000 Genomes paper, but I bet you the SNP count will be higher, because they have Khoisan in their samples (along with Mbuti, etc.). Anders shared with me some of the preliminary data that the Sanger Institute has generated.

Below the fold I plotted a PCA of the HGDP data. First, the classic SNP-chip data. Second, SNPs pulled out of the WGS which are very high quality calls (though they may still have wrong calls), but have a minor allele frequency of at least 1% (~1.5 million). You immediately notice the Eurasian compression along PC 1. Finally, using ~15 million SNPs that had no missingness in the data, you see you PC 2 being defined by San Bushmen vs. non-San-Bushmen, while Mbuti Pygmies along with Biaka clearly are the furthest along PC 1 excepting the San. There are 6 San Bushmen in the data. If there are SNPs which are very distinct to this group, and not polymorphic in other populations, then my 1% cut-off would actually remove that variation.

It’s an interesting world we live in, thanks to research groups like the Sanger Institute, Estonian Biocentre, and the 1000 Genomes Project, as well as tools such as PLINK. Analysis that took decades in the 20th century can now be whipped out in a matter of hours. Better analyses in fact.

650,000 SNPs (European ascertained)


1.5 million SNPs, 1% or more minor allele frequency

15 million SNPs, 0 “no calls”


July 29, 2018

Open Thread, 07/29/2018

Filed under: Open Thread — Razib Khan @ 10:38 pm

Reading Imperial China 900–1800 it is interesting how the Khitan seem to have chosen to develop a written script that was not based on that of the Chinese, to resist the cultural assimilation that would have inevitably occurred. Through that choice they reduced their short-term efficiency, but probably enabled their long-term persistence as a people. Certainly the Khitan seem to have remained less Sinicized on the even of Jurchen conquest than the Jurchen were on the eve of the Mongol conquest (though the Jurchen conquered North China, so they had a bigger demographic imbalance). That the Khitan continued nomadic ways is clear as they managed to reassemble to the west and fond the Qara-Khitai. The Manchu descendants of the Jurchen who conquered China seem to have been thoroughly Sinicized after a few centuries as well.

DNAGeeks going “full nerd”. If you don’t know why UGA is funny, learn some genetics! Trust me, it’s good for you. Look how I turned out.

Last Friday for whatever reason I watched Mission Impossible: Fallout. I don’t really watch films except for Marvel and DCEU stuff (I need to keep up with the culture). But I was in the mood, and I hadn’t watched a Mission Impossible since the 1996 one. Apparently Tom Cruise is really into parkour. And though Cruise has aged really well, so has Michelle Monaghan. At least Ving Rhames is still around.

I used to listen to Chapo Trap House now and then. Still do now and then. There is some stuff I agreed with, some stuff I don’t agree with that I think needs to be said, and, they are often kind of funny. But unless you are on the same political wavelength I think they do get a little stale, because they’ve got an agenda, and they need to keep revisiting the same themes. It’s a feature, not a bug.

But listen below where they contextualize the “supposed crimes” of Communism:

The issue isn’t that avowed socialists are engaging in whataboutism in relation to Communism. That’s kind of what I expect. It’s that Chapo Trap House is still part of the respectable broader Left to center-Left cultural Zeitgeist. And they’re contextualizing literal Communism.

This is the sort of stuff that pisses conservatives off whenever we point out double-standards of respectability of radical Left politics as opposed to the radical Right. If someone contextualized Nazism as a reaction to Versailles and hyper-inflation they’d be de-platformed in a second. Meanwhile, Chapo pulls in $100,000 per month on Patreon.

A special treat this week on The Insight (Apple Podcasts, Stitcher and Google Play). We talked with James Lee, lead author of Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. In the next few months we have at least one more interview relating to behavior genomics work. This is a field where stuff is happening.

Though I hope ancient DNA will start popping back up in the fall.

Big Pharma Would Like Your DNA: 23andMe’s $300 million deal with GlaxoSmithKline is just the tip of the iceberg. This was always the plan.

Out of Africa by spontaneous migration waves. Not sure if I buy this model, but we’re at more model-building stage.

A Large Body of Water on Mars Is Detected, Raising the Potential for Alien Life. This is cool.

Episode 856: Yes In My Backyard. I relate to the NIMBY activist. It’s a generational and local vs. migrant issue. Not a typical class one.

I’ve been asked to submit a chapter on a book on Indian genetics, primarily relating to the “Aryan question.” I’ve gotten most of it written, but it’s really annoying to have to wait until the Rakhigarhi preprint/paper is out. The general finding will be no surprise to a reader of this weblog. Don’t think it will be published in the USA. Perhaps I’ll post the draft at some point if the copyright allows.

Replicability of introgression under linked, polygenic selection. “Our work suggests that even highly replicable substitutions may be associated with a range of selective effects, which makes it challenging to fine map the causal loci that underlie polygenic adaptation.”

July 28, 2018

On ethnicity

Filed under: Ethnicity — Razib Khan @ 3:29 pm

A really strange conversation on ethnicity broke out below. The primacy of lots of different variables was argued.

My family arrived in the USA ~1980 when there were not too many South Asians compared to today. Additionally, they have lived in major urban areas, small towns, and medium-sized cities. My parents grew up in (East) Pakistan, married and had their first children in Bangladesh, but have spent most of their lives now in the United States of America. Both speak English with a strong accent and are moderately religious Muslims. You wouldn’t call them secular, but neither are they visibly or ostentatiously Muslim. In American politics, they are staunch Democrats, while if they have an opinion on Bangladeshi politics they are Awami League (the ratio of discussion of American to Bangladesh politics in my family growing up was about 100 to 1 in favor the former).

Today my parents’ social circle, in a relatively large urban area, are Bangladeshis. Most of these people (almost all in fact) arrived in the United States much later than they did. But in the 1980s my parents had a much smaller pool of social acquaintances who were Bangladeshi. In the early 1980s, there were 15,000 Bangladeshis in New York City. Today there are probably closer to 200,000.

Here are some things I will observe in relation to my parents’ more diverse social circles in the 1980s. First, they were overwhelmingly South Asian. Those who were not South Asian were usually married in, and usually white. Second, a core group consisted of Bangladeshis. But the next group probably consisted by Indian Bengalis. A somewhat more established community. In fact, the boundary between Bangladeshis and Indian Bengalis were somewhat fluid. The two groups spoke the same language, and there was a large dietary overlap.

Next in order to the Indian Bengalis were a variety of other social clusters of South Asians that they met through various acquaintances and friends. For example, one cluster of friends consisted mostly of people from the Indian state of Andhra Pradesh, but with a large minority from other parts of India. Because there was ethnolinguistic diversity in this social group generally everyone spoke English, rather than Telugu, which was the most numerous language.

Another group consisted of people from Pakistan and Indian Muslims. This group also had some other token Bangladeshis. The unifying factor in this group was that all were South Asian Muslims. The de-unifying factor in this group is that the non-Bengalis would sometimes make the proactive case for Urdu as a unifying language, which my parents and the other Bengalis always objected to (because of their age, almost all the Bengalis in the group could follow the conversation in Urdu, since they grew up in Pakistan).

One issue in social circumstances with Pakistanis is that my parents found the food less palatable. This was a very important criterion for them for social interactions and a primary reason why sometimes they preferred going to parties thrown by their Hindu Bengali friends in preference to their Pakistan Muslim friends. By “less palatable”, I mean here that Pakistani cuisine was not “comfort food” for them.

My parents went to a multi-ethnic mosque several times a year. From what I could tell the South Asians kept to themselves, the Arabs kept to themselves, the Turks kept to themselves, etc. There was no real deep interaction. My parents never had any close Muslim friends who were not South Asian. In fact, we went to dinner with Chinese people (my father’s colleagues) more often than we went to dinner at a non-South Asian Muslim’s house.

That’s about it from me. Below are some genetic plots.

South Asian nationalism

Filed under: Nationalism — Razib Khan @ 2:01 pm

I happen to have Saloni’s genotype and she is certainly closer genetically to Sindhis than to most other South Asians. That being said, my own response to her tweet is this: my personal experience is that many liberal Pakistani & Indian Americans are highly nationalistic.

To be honest, it’s mostly Indian Americans. I don’t know too many hyper-nationalistic Pakistani Americans. I think that has to do with the fact that despite India’s social-political problems, its democratic and pluralist history, along with the international appeal of Mahatma Gandhi, makes it easier to be an Indian nationalist than a Pakistani nationalist if you are an American.

Also, there is a cultural “code-switching” that is common among Indian Americans, where they are fluent in, and totally embedded within, a Left-of-centre cultural zeitgeist in the American landscape. But, they also are comfortable switching into their parents’ more Indian nationalist views in different contexts. Rather than synthesizing the two worldviews (which may not be possible), Indian Americans just switch facultatively between the two, because the two social milieus never really engage each other.

Because I am Bangladeshi American it is hard for me to relate. Bangladesh is a very young nation. Both my parents have spent more than 3.5 times of their life living in the United States than an independent Bangladesh. In fact, both lived as Pakistanis for far longer than they lived as Bangladeshis! Additionally, it is not a major geopolitical player, and there are ambiguities with the relationship to both India and Pakistan enough that socially my family has felt comfortable with both Indians and Pakistanis in the USA.

P.S. I do get annoyed when I’m identified as Pakistani American by people just because of my last name. Since I am not vocal about being a “Bangladeshi American” I only find out later people had assumed I was Pakistani. Apparently, in some Indian circles, I am known as a “Pakistani American geneticist”, albeit not a particularly nationalistic Pakistani (told to me by an Indian journalist friend).

Complex evolution of pigmentation in modern humans

Filed under: Human Population Genetics,Pigmentation — Razib Khan @ 1:49 pm

Last fall Crawford  et al.Loci associated with skin pigmentation identified in African populations, was published in Science and made a huge splash. As I’ve been saying recently, and most people agree, much of the remaining “low hanging fruit” in human evolutionary genomics, and to some extent, human medical genetics, is going to be in Africa on Africans. From an evolutionary perspective, that’s probably because from a gene-centric viewpoint most of our recent evolutionary history was within Africa. As a friend once told me, “most of the last 200,000 years is about the collapse of ancient population structure.” This goes too far, but at least it gets at something we’ve not been too conscious of.

Top left clockwise: Luo Kenya, Khoisan, South Asian, Arrernte Australia

Crawford  et al. was important because it was a deep dive into a topic which has been understudied, the variation of pigmentation genetics within Africa (also see Martin et al.). The fact that there is variation in pigmentation within Africa should not be surprising, though some people are surprised that there is variation in pigmentation within Sub-Saharan Africa. But anyone who has seen photos of San Bushmen, knows they are very distinct from South Sudanese, who are very distinct from West Africans. As documented by both Crawford  et al. and Martin et al. some of this variation is likely novel.

By this, I mean there has been backflow of the derived Eurasian variant of a mutation on SLC24A5. Arguably the first major human pigmentation locus of the “post-genomic era”, its discovery was enabled by its huge effect in explaining variation among Eurasian populations and their differences from African groups. In Crawford  et al. the author observes within Africans nearly ~30% of the trait variance was due to four loci, with ~13% due to SLC24A5. In earlier work comparing just people of European and African descent, SLC24A5 variance explains closer to 30% of the pigmentation difference. It seems that pigmentation effects genetically exhibit an exponential distribution. A small number of loci have a large effect, and a numerous number of loci have small effects.

Distribution of rs1426654 at SLC24A5

The results from Crawford  et al. and Martin et al., a naive inspection of the modern distribution of the derived rs1426654 allele, and ancient DNA, seem to indicate a mutation associated with lighter skin emerged after 40,000 years ago. After the expansion of non-African humans, and, the divergence between eastern and non-eastern branches of non-Africans. A common haplotype around this mutation suggests that it wasn’t part of the ancestral “standing variation” of the human lineage. Ancient samples from Scandinavia, the Caucasus, and modern samples from Eurasia and from Africa, all exhibit the same pattern, suggesting recent common descent.

And though a mutation on rs1426654 is associated with lighter skin, it does not produce white skin. I have the homozygote derived genotype on rs1426654, as does my whole nearby pedigree. All of us have brown skin, to varying degrees. And interestingly, the locus around rs1426654 seems to be under strong selection in both South Asia and Africa, including East Africa. This makes me somewhat skeptical that there is a simple story to tell on this locus in relation to skin pigmentation being the driver here.

Let me quote from  Crawford  et al.:

Most alleles associated with light and dark pigmentation in our dataset are estimated to have originated prior to the origin of modern humans ~300 ky ago (26). In contrast to the lack of variation at MC1R, which is under purifying selection in Africa (61), our results indicate that both light and dark alleles at MFSD12, DDB1, OCA2, and HERC2 have been segregating in the hominin lineage for hundreds of thousands of years (Fig. 4). Further, the ancestral allele is associated with light pigmentation in approximately half of the predicted causal SNPs…These observations are consistent with the hypothesis that darker pigmentation is a derived trait that originated in the genus Homo within the past ~2 million years after human ancestors lost most of their protective body hair, though these ancestral hominins may have been moderately, rather than darkly, pigmented (63, 64). Moreover, it appears that both light and dark pigmentation has continued to evolve over hominid history….

For over ten years it has been clear that very light skin in eastern and western Eurasia are due to different mutational events. Crawford  et al. give us results that indicate this pattern of evolutionary complexity is primal and ancient.

But there is often a tacit understanding that the selection process is the same over time and space. Something to do with protection from UV light and also synthesization of vitamin D at higher latitudes. So this paper that just came out definitely piqued my interest, Darwinian Positive Selection on the Pleiotropic Effects of KITLG Explain Skin Pigmentation and Winter Temperature Adaptation in Eurasians. The authors looked at a lot of variants in KITLG with a focus on East Asians. They confirmed that there were at least two selection events, one just around the “Out of Africa” period, and possibly another one later, during a period when West and East Eurasians were genetically distinct.

This section is very intriguing: “Besides pigmentation, KITLG is also involved in mitochondrial function and energy expenditure in brown adipose tissue under cold condition (Nishio et al. 2012; Huang et al. 2014). We demonstrated that winter temperature showed a much stronger correlation than UV for rs4073022.” Earlier the authors review work which suggests that large melanocytes are much more susceptible to damage due to cold than than smaller ones. Dark-skinned individuals tend to have large melanocytes (and more of them!). The KITLG locus does a lot of things; some of you may know its relationship to testicular cancer.

What  Crawford  et al. tells us that there seems to have been recurrent and sometimes balancing selection around loci implicated in pigmentation for hundreds of thousands of years. What ancient DNA is telling us is that the genetic architectures we take for granted as typical across much of Eurasia are relatively novel. But, I think people are perhaps taking the implications of modern genetic architecture too far in predicting the variation of characteristics in the past. Even the best genomic predictors seem to account for only around half the variance in pigmentation. “Ancestry” accounts for the rest, which basically means there are many other loci which are not accounted for. It is not unreasonable to suppose that ancient northern Eurasian populations may have been light-skinned due to genetic variants which we are not aware of.

Of course, there are people at high latitudes who retain darker complexions. From what we know the Aboriginal people of Tasmania were isolated for about 10,000 years at the same latitude as Beijing and Barcelona, and yet their skin color remained dark brown. In contrast, Martin et al. report that Khoisan people who lived 10 degrees further north, in a much sunnier climate, were selected at loci that strongly correlate with lighter skin.

I think it is safe to say that in the near future we will close in on much of the reamining genetic factor accounting for variation in pigmentation in modern populations. It is polygenic, but almost certainly far less polygenic and more tractable than height or intelligence. But the story of why humans have varied so much over time, and why loci implicated in pigmentation are so often targets of selection in some many contexts, remains to be told.

July 26, 2018

Local ancestry deconvolution made simpler (?)

Filed under: Local ancestry,Population genetics — Razib Khan @ 11:37 pm

I’ve been waiting for a local ancestry deconvolution method to come out of Simon Myers’ group for a few years. Well, I think we’re there, Fine-scale Inference of Ancestry Segments without Prior Knowledge of Admixing Groups. Here’s the abstract:

We present an algorithm for inferring ancestry segments and characterizing admixture events, which involve an arbitrary number of genetically differentiated groups coming together. This allows inference of the demographic history of the species, properties of admixing groups, identification of signatures of natural selection, and may aid disease gene mapping. The algorithm employs nested hidden Markov models to obtain local ancestry estimation along the genome for each admixed individual. In a range of simulations, the accuracy of these estimates equals or exceeds leading existing methods that return local ancestry. Moreover, and unlike these approaches, we do not require any prior knowledge of the relationship between sub-groups of donor reference haplotypes and the unseen mixing ancestral populations. Instead, our approach infers these in terms of conditional “copying probabilities”. In application to the Human Genome Diversity Panel we corroborate many previously inferred admixture events (e.g. an ancient admixture event in the Kalash). We further identify novel events such as complex 4-way admixture in San-Khomani individuals, and show that Eastern European populations possess 1-5% ancestry from a group resembling modern-day central Asians. We also identify evidence of recent natural selection favouring sub-Saharan ancestry at the HLA region, across North African individuals. We make available an R and C ++ software library, which we term MOSAIC (which stands for MOSAIC Organises Segments of Ancestry In Chromosomes).

The truth is I’ve only done a quick skim of the preprint and not run the method myself to see how it works. But to be honest I can’t see where the part about Eastern Europeans is in the manuscript (I checked the supporting text)? That being said, if you run a PCA many Northern and most Eastern Europeans are clearly shifted toward East Asians compared to Southern Europeans. So I accept it.

In any case, always remember, all models are wrong. But some of them have insight.

Render unto Caesar worldly goods

Filed under: History,Religion,Secularism — Razib Khan @ 11:11 pm

At Tanner Greer’s recommendation, I purchased a copy of Imperial China 900-1800. Now that I’ve received it I realize that I read a few chapters of Imperial China 900-1800in 2008, before abandoning the project due to sloth. Older and wiser.

As I’m reading this book, I’ve been giving thought how I would respond to this comment:

…not only were priests an independent power source from kings, but no matter how deeply interrelated each was in principle independent of the other, with their own independent spheres: the secular sphere and the religious sphere. This fact too was important in shaping the modern world, in that modernity assumes that government is fundamentally secular in a way that would have been unfamiliar to pre-moderns outside of Latin Christendom.

This is a common view. Fareed Zakaria, for example, expresses something similar in The Future of Freedom, whereby the emergence of an independent Western Church after the Fall of Rome created space for secularization and the development of liberal democratic institutions through decentralization of power.

And yet after having just read History of Japan, and reading again about the Battle of Anegawa, where Oda Nobunaga completed a chapter of his crushing of institutional Buddhism as an independent power in Japan, I wonder what the above even means. A standard model would argue that in East Asia religion suffused life, philosophy tended toward monism, and there was no separation between this world and that. The Emperor of Japan descended from the Sun Goddess. The Emperor of China was the Son of Heaven, though Heaven was not conceived of in an anthropomorphic sense. And yet the kingship of nations such as France and England have exhibited a sacral nature, and to this day the monarch of England is also the head of its established religion.

About when I abandoned my plan to read Imperial China I read Jay Winik’s The Great Upheaval: America and the Birth of the Modern World, 1788-1800. One of the many things that stuck with me from that book was just how radical in regards to religion the federal government established by the American Founders was at the time. While the American states had all had an established religion, due to the pluralism of the new nation, and the personal secularism of many of the Founders, no consideration was given to privileging religion on the national level. This concerned many leading thinkers, some of whom suggested that simply declaring Christianity in the general sense the national religion would have been sufficient (and for all practical purposes Protestant Christianity was the national religion, even though church-state separationists such as Andrew Jackson were punctilious in making this not a de jure matter).

With hindsight, it seems clear that having a “national religion” only makes sense in the aftermath of the Protestant Reformation, and the collapse of the religious system of Western Christendom during the medieval period. The medieval Western Church was characterized by a great deal of diversity and variation. But something happened during early modernity, whereby that variation produced too many tensions and factionalized. Eventually, this shattered the tacit understandings and compromises which allowed for external unity. In nations where monarchs supported Protestant Reformers, national churches emerged, and become official arms of the state for all practical purposes. In Catholic Europe, a reaction produced a newly muscular and standardized church, which stood opposed to the new official Protestantism on very similar terms. The Roman Catholic church remained international, but it also became the national churches of nations as diverse as Poland, Ireland, and Spain.

Though many people assert that the Roman Empire became “officially” Christian with the conversion of Constantine, or perhaps during the reign of Theodosius the Great at the end of the 4th century, the reality is that the Roman Empire was not a totalitarian state. The dissolution of paganism occurred more through slow decay and death, as the cessation of subsidies from the state starved elite paganism, and persistent missionary efforts blanketed the population with nominal Christianity.

The assertion above that “government is fundamentally secular in a way that would have been unfamiliar to pre-moderns outside of Latin Christendom” always strikes me as strange because of my familiarity with Chinese history and philosophy, and the interpretation of how the Chinese seem to have viewed “church”-state relations. It is often said that the Chinese are superstitious, but not religious. In other words, what China lacked in the vigor of organized religion, it made up for in widespread belief in supernaturalism. This is broadly correct, but the same could be said for the West for most of its history. That is, many pre-modern peasants were not religious as much as they were superstitious, and their Christianity was a thin skein upon folk beliefs.

The issue rather is with the cultural elite, and what their beliefs were. There is a line of argument that philosophical dualism, and a particular sort of disenchantment with the world and a rationalism, was pregnant within Western Christianity, and came to fruition with Calvinism and modern forms of Catholicism. In the ancient world, Christians believed that magic was real, and that the pagans worshipped true supernatural forces, but that these were rooted in the devil. The argument proceeds that in early modernity this belief gave way to more rationalist views, whereby God remained true, but non-Christian beliefs were rooted in falsehood, rather than demons. Magic was now simply trickery.

And yet History of Japan notes that even before Oda Nobunaga’s crushing of the Buddhist clerical powers of the 16th century the society was going through broad secularization, as popular and elite enthusiasm for religion abated. Though the Tokugawa regime enforced Buddhist registration by families across Japan, this was a measure that enabled control and regulation, not one which promoted religion as such. Japanese intellectuals during this period were influenced by currents skeptical of supernaturalism that had its roots in Chinese Confucianism, and this in its turn can be found to have prefigured by anti-supernaturalist threads as far back as Xunzi.

Curiously, the Japanese system after the decline of the Fujiwara and the rise of the Shogun dynasties recollects the mythologies of dual kingship, with a sacred and a secular king, in other societies. To me, this reinforces my own current position that all the semantical distinction between secular and sacred power and how they differ between societies elides more than it illuminates. My own materialist bent leads me to suggest that in fact, secularization in early modernity at the two antipodes of Eurasia were natural and likely inevitable developments with mass societies and more powerful states. A coercive state did not need to rely on supernatural power to persuade a populace, and the workaday nature of bureaucratic governance, in any case, would not reflect positively upon a religious order that was fused with that state.

Naturally, others will have different views. But one of the reasons I am such a fan of Peter Turchin’s project is that I tire of semantic definitions as the axis around which arguments hinge. I am usually unconvinced by the erudition of my interlocutors because in most cases I don’t get a sense that they know more than I do, even though perhaps they may, in fact, be in the right. Rather than calculating, argumentation is often a way for two individuals to assess each other’s knowledge base and sophistication. If there is parity, there will never be a resolution, because personal qualities are more relevant than reality.

July 25, 2018

East Bengal/Pakistan catches up to West Bengal/Pakistan

Filed under: Economics — Razib Khan @ 9:48 pm

Today I was looking on the internet to get some more information on the Pakistan election. Honestly, I don’t have a strong opinion….

But by chance, I ended up stumbling on articles like this, When East overtakes West:

…a recent article, “East overtakes West,” in The Economist has thrown a spanner in the works. The east is the erstwhile East Pakistan and the west is today’s Pakistan. It shows that the GDP per capita of Bangladesh is $1,538 and that of Pakistan lags behind at $1,470. This is the result of a GDP growth rate of over six per cent per annum in the past 12 years. One-third of the GDP is contributed by industry and the value-added garments exports are larger than India and Pakistan put together.

The truth is that Bangladesh’s better statistics in some measures are due to demographics. Per capita values will change in opposite directions if nation underestimated its population (as Bangladesh did), and another nation overestimated its population (as Pakistan did). Using PPP corrections and such Pakistan is still a more prosperous land per person. But it’s getting close. The trendline is definitely pointing in one direction. A piece at Brookings asks “Why is Bangladesh booming?” The author notes:

Once one of the poorest regions of Pakistan, Bangladesh remained an economic basket case—wracked by poverty and famine—for many years after independence in 1971. In fact, by 2006, conditions seemed so hopeless that when Bangladesh registered faster growth than Pakistan, it was dismissed as a fluke.

But I’ve always thought that the infant mortality and life expectancy statistics in Bangladesh were things that were more important to be proud of (and on this score Bangladesh does indisputably better than Pakistan). And curiously, on this measure, Bangladesh does even better than India! But to a great extent, that’s not a fair comparison, as India is a coalition of regions, while Bangladesh would just be a very populous Indian state.

More comparable is West Bengal. Bangladesh and West Bengal look to be at parity in terms of life expectancy and per capita GDP. And metropolitan Dhaka and Kolkotta now have about the same population, at ~15,000,000.

We live in interesting times.

The Insight show notes: episode 30, Genetics and educational attainment

Filed under: Education,Genetics,Psychology — Razib Khan @ 3:47 pm

This week Razib and Spencer discussed the relationship between educational attainment and genetics on The Insight (Apple Podcasts, Stitcher and Google Play) with James Lee, lead author of Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals (published in Nature Genetics).

Here are some more resources: FAQs about “Gene discovery and polygenic prediction from a 1.1-million-person GWAS of educational attainment”. The Atlantic and The New York Times also covered the paper. An op-ed in The New York Times, Why Progressives Should Embrace the Genetics of Education.

The three laws of behavior genetics and the fourth law of behavior genetics are both mentioned. The study was a meta-analysis of genome-wide associations (GWAS), and may have been the largest GWAS published to date.

Much of the discussion centered around intelligence. The podcast with Stuart Ritchie was cited as a useful primer (remember to subscribe with Apple Podcasts, Stitcher and Google Play). You might want to check out Ritchie’s book, Intelligence.

Population stratification was mentioned. Martin et al., and two preprints, Berg et al. and and Sohail et al., tackle this issue in relation to disease and height, and how it confounds our understanding. Lee discussed LD score regression as a way to account for stratification in this particular analysis..

There was extensive discussion of the concept of heritability, where genetics explains variation in a trait.

The Social Science Genetic Association Consortium (SSGAC) and its research projects were referenced extensively.

Each allele seems to effect ~1 week of education. The authors returned more than 1,000 statistically significant markers.

Spencer brought up the “omnigenetic” model. This comes from Boyle et al., An Expanded View of Complex Traits: From Polygenic to Omnigenic.

James mentioned some of Camille Benbow’s work, in particular Life Paths and Accomplishments of Mathematically Precocious Males and Females Four Decades Later.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!

The Insight show notes: episode 30, Genetics and educational attainment was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

July 23, 2018

Open Thread

Filed under: Open Thread — Razib Khan @ 9:12 pm

Please keep the other posts on topic. Use this for talking about whatever you want to talk about.

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