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A Collection of Interesting, Important, and Controversial Perspectives Largely Excluded from the American Mainstream Media
Gene Expression Blog

51TpAsC5UlL._SY346_FiveThirtyEight and New York magazine have pieces which look at the prosperity which was the norm in the second half of the 1990s with a soft glow. I was not in the labor market back then, but I recall the excitement, and just how easy it was to get a job for those who wanted one. It seems that these articles reinforce the basic thesis of Tyler Cowen’s Average is Over, looking back to the last golden age for the middle class.

But there’s another angle on this. Would you go back to 1999 if you had twice the income you did today? Probably that depends on your income. But imagine going back to the technology of that era. For many of us the world would be a sluggish and gray place. Cowen would point out that this is not the typical person. But it’s a lot of us, and it isn’t as if smartphones and their various features are low penetration technologies in terms of cultural ubiquity. So a simple apples to apples comparison of income is somewhat misleading. Because of rising demand from China I’m not sure that decreasing expenditures on food is sustainable (though perhaps better GMO would help in that domain). But it does seem to me that public policy is what’s keeping housing prices high, in particular in Blue State urban areas. Make the libertarians happy by getting ridding of rent control. Make the conservatives happy by allowing more sprawl. Make the new urbanists happy by allowing more vertical residential housing.

I think the bigger issue here is not economic, but social. Economic productivity is such that a guaranteed minimum income is probably viable for society. A minority may work so that the majority may eat and recreate. But human psychology is such that it seems implausible that a democratic citizenry can be maintained by passive consumption by those who themselves are not economically productive. Many of these discussions about the passing of the middle class society focus on economic well being, or lack thereof. I don’t think that’s the major issue at all, because economic productivity will continue to increase, at least on the margins, and population growth outside Africa has tailed off. Rather, the larger change will be cultural and social. Even in antiquity when societies were highly stratified the great thinkers understood that social well being rested upon the broad shoulders of the free peasantry, who were the ultimate source of most economic activity. This is very different from the model of stratified societies of the future, where both power and productivity will be concentrated nearer the top of the status distribution.

• Category: History • Tags: Economics 

Obviously colored by my interests.

• Category: Science • Tags: ASHG 2014 

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In the Big Apple

I’m very excited to be going to ASHG this year. The last time it was great meeting people like Luke Jostins‘ for the first time (and re-meeting people for the second or third time). Also, the posters and talks gave a preview of things which came out later in the year, so the cost of attendance was certainly worth that. I dig genetics. This time I’m going to be in San Diego, a city that I’ve never been to. Excited to explore a little if I have time. Though despite what I’ve said on Twitter I am not going to Tijuana. But speaking of fun, if any reader knows of after hours parties, etc., I’d appreciate it if you’d hook me up. I’m actually a kind, gentle, and fun person in real life who is not a bad dancer (people seem to think I’m mean and brusque from my internet persona; this has been brought up to me by several people after they’ve met me).

Below are the sessions, etc. I’ll be going to if anyone wants to try and assassinate me in broad daylight (that’s a joke, not an invitation).

• Category: Science • Tags: ASHG 
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Credit: A friend of Razib

I’ve been avoiding focusing too much Oxford Nanopore over the past few years. Privately I do ask people smarter than me/”in the know” if they think that the technology is the real deal. The reason for my skepticism is that I remember people being hoodwinked by Pacific Biosciences in 2008. Part of the issue is that biologists want these technologies to deliver, so there’s a bias in terms of how they’re going to be received.

That being said I saw some Nanopore machines recently. I knew they were small. In fact, rationally I knew how small they were. But when they were just there on the counter, like large USB drives, it was hard to take it in. The new Illumina machines aren’t very large. They’re mini-fridge scale. But to see a sequencing machine which you might actually step on by mistake was a bit mind-blowing. It’s as if we’re going from 1970s mainframe technology, where it took up a whole room, to the smartphone era, where a computer fit in your back pocket.

I don’t know if Oxford Nanopore will succeed. But it seems obvious, viscerally so, that someone will, and that we’ll have small portable sequencers which are quite accurate and will generate long reads by 2020. That’s a revolution, but by then we’ll probably take it for granted. Then we can forget about the technology, and focus on the biology and what to do with all the data.

• Category: Science • Tags: Genome Sequencing 
Brawand, David, et al. "The genomic substrate for adaptive radiation in African cichlid fish." Nature (2014).

Brawand, David, et al. “The genomic substrate for adaptive radiation in African cichlid fish.” Nature (2014).

A new paper on cichlid evolutionary genetics in Nature is pretty interesting. It’s open access, so everyone can read it, The genomic substrate for adaptive radiation in African cichlid fish:

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Reading a paper like this makes it very clear to me why organismic information is very critical in trying to understand evolutionary processes. R. A. Fisher was a great scientist, but his attempt to create very general rules for evolutionary processes as outlined in The Genetical Theory of Natural Selection seems quixotic in hindsight. As a professor of mine once said “biology is the science of exceptions.” This is probably one reason that the old 19th century vogue for creating “laws” went into decline; laws are useful only when the exceptions to them are very few. The diversity and specificity of evolutionary biological processes is why I think arguments in the form of dichotomies are in vain. For example, “selectionists vs. neutralists” or those who argue for the primacy of contingency in evolutionary outcomes, or those who favor convergence toward deterministic outcomes. It strikes me that the answer to all these questions must be predicated by the phrase “it depends….”

electr10The story of African cichlids is relatively well known. You have a huge range of phenotypic outcomes which seem to be the result of relatively recent diversification. Not only that, but cichlids look cool. The question though is what can this tell us about evolution? The paper does a lot of genomic slicing and dicing of a few select lineages. Before we knew about genes the nature of transmission in evolution was something of a black-box. With DNA that changed, and now with genomics we can look at how various features differ across lineages and over time. For example copy number variation, coding regions, regulatory elements, and characters more abstruse to those outside of genomics, such as LINEs. Sequencing a bunch of cichlids gets you a publication in Nature, but that’s not the point of it all. The point is what does it tell you about evolution, at least in this case?

Basically it seems that cichlid radiation has occurred due to selection on the natural genetic variation across many loci that already existed in the ancestral lineage. It was easy enough to type, but in some ways this reality is a bit difficult, in that classical models of selection were often predicated on new mutations emerging in the genetic substrate, and rapid sweeps to fixation from the original mutant form. A human illustration of this is lactase persistence, which seems to be due to a change in gene regulation via a new mutation that arose ~5,000 years ago, and quick swept to near fixation across many diverse human lineages. This sort of phenomenon is like striking a hammer at the genome; it leaves a big mark which is easy to detect. In contrast to hard selection, soft selection on standing variation operates across many loci, and rather than a novel genotype in a singular sense produces a change in underlying allele frequencies. In some ways this is more classical Darwinian, but it also generates more work and is not as elegant as a simple model of a hard sweep from a new mutation. But that’s just how it is. At least in the cichlid lineage.

41SWwcvSm6L._SX258_BO1,204,203,200_ Actually, I suspect that’s how it is in many complex organisms. For a human illustration, see The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation. I’m betting that it’s also the norm among our many domestic animals. For example rabbits. A few years ago at a conference Claire Wade reported that the focus on traits and genes with disjoint distributions across dog breeds had obscured the reality that much of the variation in this lineage is still shared, and there is probably a lot of soft selection on polygenic traits going on.

So the near future is in quantitative traits, and natural selection reshaping the variation which is already present in lineages. Perhaps people should start re-reading Genetics and Analysis of Quantitative Traits. And as a weird side effect, if I was interested in such things I bet that the emphasis on selection from standing variation probably supports philosophical monism. All is one. Or something.

• Category: Science • Tags: Evolution 

As you all know by now the eligible electorate of Scotland has voted “No”, against independence. At least 55 percent has. I think that the fact that this has occurred relatively peacefully and in a civilized manner should be edifying to all. Though I do not have great passion on this subject, I am broadly sympathetic to separatist movements within the European Union, as it strikes me that the existence of the European Union itself obviates many arguments for the gains of being part of a larger nation. Scotland though differs from the Catalans in that the United Kingdom is not part of the Euro, and the claims by the Scottish independence camp as to their ability to remain with the pound did strike me as disingenuous. In fact, I found the “Yes” camp ludicrous in terms of their economic arguments, and the “No” camp quite sensible and conservative in the literal sense. I am not particularly sympathetic to social democracy, and much of the pro-independence elite seems to have been arguing that their goal was to transform Scotland into a Nordic welfare state. But economists more sympathetic to the welfare state are also confused as to the cost vs. benefit calculation.

The issue here is that sometimes a cost vs. benefit calculation is not the point. The global elite, high earning cosmopolitans extracting incredible gains from free flow of capital, goods & services, and people, feel the modern nation-state to be simply a device which exists to enact and execute laws which can serve as a framework for the free market. In other words, the nation is a means toward economic welfare. From that perspective Scottish independence seems irrational. But the average Scot is not a part of the global elite. Of course the pensioners and much of the middle class seems to have voted against independence, so one can’t assert that resistance to separatism is just a feature of the wealthy elites. But it does seem likely that a larger proportion of those who voted “No” were voting to keep what they have, rather than looking toward future gains. It wasn’t passion or enthusiasm, but prudence. A bourgeois virtue, which has its points.

But a nation is more than the sum of utils. Would anyone ask that soldiers should sacrifice their lives for productivity gains? Should Britain have yielded to Germany in 1940 because of rational calculations? Or more to the point should the Scots have bowed down before bourgeois, when it seems clear that the odds beforehand were against them? What the global elite seems to not comprehend when facing ‘irrational’ nationalism is that their opponents do not share their premises. In the developed nations of the West there is a sense of ennui due to the lack of motivating spirit. The goal of economic well-being above and beyond basic needs has long been met. Now it is on to the bigger house, the bigger car, and so forth. This rush toward competitive consumption results in short term happiness, but it is often ultimately empty. The cosmopolitan elites may be wealthy in money, but they are also often wealthy in life satisfaction because of the nature of their careers, and the experiences which they can indulge in. They do not comprehend the vacuousness of the lives of the middle to lower classes, because they live lives with verve and excitement. But at some point they will have to face the reality that the 90 percent do not exist purely as means to the ends of the 10 percent. If a system is not sustainable, it will not be sustained.

• Category: Ideology • Tags: Nationalism 

k10064 So how do you tell that fall is arriving in California? Sunset arrives earlier. Real explanation from a friend who is a California native. In any case, in my few spare minutes I’ve been reading Lost Enlightenment: Central Asia’s Golden Age from the Arab Conquest to Tamerlane. Probably would not recommend for a novice, and to be honest the author is a little prolix. But it’s a nice complement to more general works such as When Baghdad Ruled the Muslim World: The Rise and Fall of Islam’s Greatest Dynasty, where the ‘eastern interlude’ received some attention, but probably far less than warranted in relation to how significant it is to world history. One aspect of of Lost Enlightenment which a general audience would benefit from is that it emphasizes just how important and disproportionate Iranian speaking intellectuals from Turan were during Islam’s Golden Age in terms of reach and influence. Many of the thinkers that one might assume are Arab because they wrote in Arabic turn out to be ethnically Iranian, and from the further reaches out of the Iranian world, beyond Persia proper.

51YU-l46UbL._SY344_BO1,204,203,200_ I do feel a little guilty that I’ve not finished off Matthew Stewart’s Nature’s God: The Heretical Origins of the American Republic. The problem is that I’m in broad agreement and in overall familiarity with the ideas and theses presented within Stewart’s work. Historical perspective matters, and it was Jay Winik’s The Great Upheaval which brought home to me just how metaphysically radical the Founders were in their time. I had read The Godless Constitution years before, and it seems clear that the relative thinness of religious character in the founding documents of early American republic was no inadvertent lacunae. But Winik’s treatment brought home just how strange it was for a polity to arise without any imprimatur of religious sanctity. Stewart’s work is timely, insofar as the ideas of charlatans such as David Barton have received wide attention, but aside from the threads of connection with the ancients such as Lucretius it isn’t fundamentally a new story. It has long been known, as far back as the accusations against Thomas Jefferson of being an infidel.

download Finally, I now have Armand Leroi’s The Lagoon: How Aristotle Invented Science. I’m excited to read this, because since Mutants I have felt that Armand is a writer of science on the same level as Richard Dawkins. It turns out that we’re interested in the same things, and I actually am highly sympathetic with the subheading of his latest book, but the fact is that Armand just writes well. I can recommend this book without even reading it, and I’m looking forward to reading it in a few settings next week, when I’m going to try and take some time off from the inter-webs and my various adult professional obligations.

• Category: Miscellaneous • Tags: Open Thread 

k9958 A new piece in Slate, Life Is Random: Biologists now realize that “nature vs. nurture” misses the importance of noise, makes a point which I’ve long been making: a lot of “environmental variation” is actually random, basically “noise”. I’d probably take issue with emphasis of the thesis, as I don’t quite think that the understanding of the role of noise in biology is quite so novel as the author makes it out to be. The headline does not help, though that probably can’t be attributed to the writer. Anyone who has worked in biology is well aware that many of the processes we attempt to understand are just really hard to tackle because of the overwhelming background noise against which we’re trying to pick up signal. Jim Manzi would term this “high causal density.” Social scientists have the same problem.

But it’s the last paragraph which really jumped out at me as notable:

Genetic determinism is the view that our genes make us who we are. Popular articles abound describing genes for daredevilishness, creativity, empathy, even being a Republican. Futurists and science-fiction authors predict that genetic engineering will someday allow designer children, built to order, with whatever smarts, looks, and personalities their parents prefer. But biology’s new recognition of the role of noise in development gives us one more reason to think that this simply isn’t going to happen. Gene mapping can’t tell you whether or not your kid will be a skydiver or a conservative, because gene expression is a far more complex phenomenon than biologists long imagined. Even if we can get the genes right, and somehow completely control environments, there will always be noise to make life richly unpredictable.

As I said above I’d take issue with the style of the exposition, as it makes the discovery of noise far more sensational and amazing to contemporary biologists than it is. But much of the substance, down to the illustration of randomness via elegans, I’m wholly on board with. But the author of the Slate piece leaves us with a very different moral than I usually do. She seems positively desirous of the rich creativity energy which noise injects into the developmental process. For me, on the contrary, the power of noise to mess with our expectations means that you have to emphasize even more those variables which have some understanding of. Genes.

• Category: Science • Tags: Genetics 
Citation: Nature 513, 409–413 (18 September 2014) doi:10.1038/nature13673

Citation: Nature 513, 409–413 (18 September 2014) doi:10.1038/nature13673

Ancient human genomes suggest three ancestral populations for present-day Europeans has finally be published in journal, Nature. This is important as a validation and confirmation of the strange results which were reported therein. One simple finding which I haven’t commented on in too much detail is how clearly Europe as a biogeographic entity is distinct from the Near East genetically. Arguably, it’s more than a cultural construct. Europeans share descent in part from an ancient lineage which dates to the late Pleistocene, and is not shared with those outside Europe (haplogroup I-M70 in Y chromosomes). To an extent this isn’t totally surprising, as water barriers are often incredibly good at allow for populations to drift apart due to lack of reoccurring gene flow (even ones as narrow as the Straits of Gibraltar and the Bosporus). On the other hand there is arguably more continuum with populations in Northeast Asia, though much of that is relatively recent in vintage (e.g., many of the Central Asian Turkic groups occupy a position between west and east Eurasia, but they are relatively recent admixtures).

Finally, this paper leaves a lot of unanswered questions, which I suspect will be answered soon:

Several questions will be important to address in future ancient DNA work. One question concerns where and when the Near Eastern farmers mixed with European hunter-gatherers to produce the EEF. A second question concerns how the ancestors of present-day Europeans first acquired their ANE ancestry. Discontinuity in central Europe during the late Neolithic (~4,500 years ago) associated with the appearance of mtDNA types absent in earlier farmers and hunter-gatherers raises the possibility that ANE ancestry may have also appeared at this time. Finally, it will be important to study ancient genome sequences from the Near East to provide insights into the history of the basal Eurasians.

One thing to note about “basal Eurasians” is that they claim that it shares “drift” with all other non-Africans. This implies that they were not post-Out-of-Africa migrants from Sub-Saharan Africa, but shared in a common Out-of-Africa history with the other populations of the world. I hope that deeper study of non-European populations might be able to get us a better sense of where basal Eurasians shake out.

• Category: Science • Tags: Europeans 

Darwins-Cathedral-cover Recently Sam Harris rebuked President Obama’s assertion that the Islamic State is “not Islamic.” And also that “No religion condones the killing of innocents.” To not put too fine a point on it, these statements are either false or meaningless. I applaud Harris as far as it goes, as he is willing to unashamedly rip the veil off the sophistry which dominates much of our public discourse. But in many ways Sam Harris is to atheists what Thomas Frank is to liberals. He is sincere, but his power is in rhetoric rather than analysis.

On the face of it the Islamic State is clearly about Islam. Islam is in its name, and they gesture toward many of the traditions and tropes of that religion. But to reduce the Islamic State to something as vague and expansive as being due to Islam is not particular informative or insightful. This sort of civilizational-culturalist explanation resembles the aether in its formless ability to reshape itself to any phenomena. A key fact which I think is essential in attempting to understand the nature of the Islamic State is that ex-Baathist officers and functionaries have been essential in the operation of the nascent state. This is interesting because Baathism was notionally a secular ideology, co-founded by an Arab of Christian background. But one thing I have read is that even non-Islamist Sunni insurgents in Iraq in the aughts became progressively more religious in their orientation. The eventual absorption of this element into the Islamic State is then an evolutionary process of slow co-option of a marginalized component.

If the function of the Islamic State as a state, as opposed to a diffuse terrorist network, is contingent upon the resurrection of the old Baathist power elite, then one can posit the hypothesis that its emergence was contingent upon the total dispossession of that elite after 2003. Clearly the Sunni Arab hegemony of the Baathist period was not sustainable, but the total dissolution of all the old institutions, and the marginalization of stakeholders, was not inevitable. A falling back to old, atavist, identities by these officers is not entirely surprising. Consider the ethnic nature of most prison gangs. These men on the run, stripped of all material comforts, naturally were drawn to a less concrete, more ‘aspirational,’ ideology.

• Category: Ideology • Tags: Islamic State 
Credit: Razib Khan, taken at the Metropolitan Museum of Art

Credit: Razib Khan, taken at the Metropolitan Museum of Art

I took the above photo at the Met in New York. What did you think when you saw the image initially? You can read about the detailed meaning of the statue, but the short explanation is that it’s a Native American girl who stumbles upon a cross. Before 2010 the pose wouldn’t trigger any strong connotations associated with popular culture, but today it does.

• Category: Miscellaneous • Tags: Art 

Discuss anything.

• Category: Miscellaneous • Tags: Open Thread 

When I was watching Boyhood I assumed that some moron would point out that the protagonist’s social milieu was overwhelmingly white. And it’s out: Not Everyone’s Boyhood. Many of my friends have a hard time accepting I identify as conservative, but reading stuff like this makes it clear why I’m conservative, I feel like puking over this sort of critique because I think it’s totally dishonest. I feel confident that most of the white writers at The Atlantic, where the piece was published, had white childhoods, with white friends. If you look at the General Social Survey, and I have, around 50 percent of white liberals haven’t had a black person over for dinner in the last few years. And there was the media buzz recently about the fact that white people have white social networks. A clear case of “no shit” social science.

That is all fine. The writer of the piece on Boyhood is someone named Imran Siddequee, who is I’m sure working hard to make a career as a race hustler. And that’s good as far as it goes. If you majored in the humanities you have to make a living somehow. Not to be racist, but what really bothers me is the amen chorus of white liberals who deconstruct and denounce all manner of cultural production for its lack of “diversity”, but who live lives as populated by white people as the protagonist of Boyhood. As it happens I have a lot of white friends, and sometimes on Facebook you see wedding photos. Most of my friends are liberal, though not all, and one thing that is salient is that these wedding parties and attendees are mighty white. Even in California, where half the population is non-Hispanic white, good white liberals seem to be inviting only white people to their seminal life events.

So I’m proposing the “wedding test” to see if you really walk the walk on diversity and all that. You don’t have to marry someone of another race, I know that’s going too far for most people (recalling the Reihan Salam column in Slate where comments analogized same race preference to sexual orientation). But if diversity is really something you value, presumably that will be reflected in the few hundred people you invite to your wedding party. Change starts at home, if you can’t diversify your personal life, perhaps you should get off your high horse about how we need “more diversity in field X.”

• Category: Race/Ethnicity • Tags: Race 

birth_cover_500 Gary Marcus’ The Birth of the Mind keyed me in to the fact that claims of neural plasticity often also suggest that the brain can not completely compensate for alterations structure. This was relevant in his discussion of mental modularity, but it is something to keep in mind whenever you encounter “amazing” instances of people who survive damage to their brain. A case in point, Woman of 24 found to have no cerebellum in her brain:

… woman has reached the age of 24 without anyone realising she was missing a large part of her brain. The case highlights just how adaptable the organ is.

The discovery was made when the woman was admitted to the Chinese PLA General Hospital of Jinan Military Area Command in Shandong Province complaining of dizziness and nausea. She told doctors she’d had problems walking steadily for most of her life, and her mother reported that she hadn’t walked until she was 7 and that her speech only became intelligible at the age of 6.

Yes, a case of the adaptability of the brain. But she still has problems walking steadily, and that’s not a trivial matter for an “upright ape.” The structures of our brains are not coincidence, which can be discarded without consequence.

• Category: Science • Tags: Neuroscience 

If you’ve been reading this weblog this headline in Science won’t be surprising, Three-part ancestry for Europeans. The writer, Anne Gibbons, draws up stuff which has been out for a long time (e.g., Ancient human genomes suggest three ancestral populations for present-day Europeans). But she also has taken the temperature of researchers in terms of where the results are going, as obviously there are hunches and inferences the scientists are making which are not publication worthy, yet. From the article:

How do you make a modern European? For years, the favored recipe was this: Start with DNA from a hunter-gatherer whose ancestors lived in Europe 45,000 years ago, then add genes from an early farmer who migrated to the continent about 9000 years ago. An extensive study of ancient DNA now points to a third ingredient for most Europeans: blood from an Asian nomad who blew into central Europe perhaps only about 4000 or 5000 years ago. This third major lineage originated somewhere in northwestern Asia, perhaps on the steppes of western Asia or in Eastern Europe.

Previous studies have also found some genetic ties between Europeans and Native Americans, notes population geneticist Wolfgang Haak of the University of Adelaide in Australia, a co-author on the new study, a draft of which is available on a biology preprint server. Thanks to these ancient Eurasians, “someone with northern European ancestry is more closely related to Native Americans than southern Europeans are,” says Pontus Skoglund, a postdoc at Harvard who analyzed DNA from the Swedish skeletons but was not a co-author.

In their talks, Haak and Krause each proposed that the late influx of these “ghost” Eurasians might be related to what’s known archaeologically as the Corded Ware culture of nomadic herders, who imprinted twisted cord or rope onto their pottery. These nomadic pastoralists herded their cattle east from the steppes north of the Black Sea and occupied large areas of northeast and central Europe by 2500 B.C.E.

Frequency_of_R1a_in_EuropeSo now we have a name, the Corded Ware. This is not archaeologically entirely surprising, though what little I know has been gleaned from Wikipedia. Those more versed in this domain can now offer their own interpretations of the implications, but I’m rather sure that the geneticists are confident about their results if they’re floating it about, and have probably cross-checked with some archaeologists. I do think though that we know have a sense of why R1a is so frequent across much of Europe. It doesn’t show up in the ancient DNA, but probably came with Corded Ware.

• Category: History • Tags: Corded Ware 

twohigIQkidsThe new paper in PNAS, Common genetic variants associated with cognitive performance identified using the proxy-phenotype method, has resulted in a fair amount of reaction. One of the major things that people grasp onto is that the effects of the variants in question are extremely smaller (here’s an FAQ for the current paper). Each variant is associated with a 0.3 increment or decrement in IQ, where the average IQ is 100 and the standard deviation is ~15 points. These results are not surprising, as the problems with earlier attempts to fix upon a genetic region which explains a great deal of variation in intelligence in the normal range have not been successful (i.e., they fail replication, so probably just a false positive). Taking these results at face value many have wondered what the big deal is, as the associations here have such a small impact.

First, a small effect does not preclude important practical consequences. The locus HMGCR has been implicated in variation in cholesterol levels at 0.1 standard deviation, but that is the locus that statins target. Does this mean that we can make a “genius pill” in the future? I’m moderately skeptical, and obviously there are major ethical issues with this. But, this sort of research shows that it may be possible, and in this big wide world of ours knowledge is hard to keep under control. As a normative matter I’m in the always better to know category for almost everything. So big surprise I have no issues with this line of research.

There is a second issue of more practical relevance, and that is that many people wish to reject a heritable component for intelligence. To be clear it is robust science that intelligence is 0.3 to 0.7 heritable. That means that 30 to 70 percent of the variation in intelligence in the population is due to variation in genes. Because the trait is highly polygenic, on the order of thousands of loci controlling variation in intelligence, it is difficult to pick any particular signal. But very few scientists are under the illusion that intelligence is not at least moderately heritable. A good analogy here is height, which is highly heritable, and controlled by many genes of small effect (the genetic architecture here is moderately more tractable from what I can tell). But for many people, especially in the public, they “need a gene.” It makes the abstract, ratio of additive genetic variance over total phenotypic variance, concrete.

But I find it more interesting that some are spinning this as a support for the low heritability of IQ, and the importance of environment. Personally I wish for my children that environment was less important, not more. The reason is simple: in a behaviour genetic sense we really don’t know what we’re talking about when we say “environment.” The Invisible Gorilla has a lot of illustrations on how tools and techniques which make us “smarter” really don’t work (or, their efficacy has not been scientifically validated). The same for infants and children. Obviously malnutrition and abuse are going to cause problems in relation to development, but the sort of “enriching” activities and practices de rigueur among upper middle class parents probably are irrelevant to the final outcome of the trait in question (this is clear when you look at the high level of variation cross-culturally, with some “best practices” being contradictory, but the results are the same nonetheless).

The-Nurture-Assumption-Harris-Judith-Rich-9780684857077 The best way to think about it is that “environment” is just noise in your model. It is the genetic component you can control, or at least use to predict. Though heritability is a population wide statistic, it has some relevance for individuals. The mid-parent value of a trait for the parents can help you gauge your expectations for your offspring. When you standardize for sex the height of parents can tell you whether to expect tall or short offspring. This is not guaranteed, as there is a high standard deviation around the expected value, even for a highly heritable trait like height (the correlation between full-siblings for height is ~0.50). But, it does load the die. The correlation of IQ between full-siblings is also on the order of ~0.50. Remember here that environment, the noise parameter, changes your expected value. Since this isn’t heritable it drives the phenotype of the offspring back to the population mean. If IQ is less heritable, say 0.30, then if you and your spouse are deviated away from the mean, you can expect your children to regress back to the population mean, since they won’t inherit the magic mix of factors which resulted in high IQ. In contrast, if IQ is heritable on the order of 0.70, then you can update your expectations so that your children will be more likely to resemble you, assuming you are deviated from the norm.

Perhaps I’m a narcissist, but I want my children to be like me in cognitive profile. It makes it easier for me to understand where they are coming from. If I thought that I could as a parent control the environmental outcomes with a high degree of certainty I might be more sanguine about low heritability, but that’s not my hunch about this trait. Low heritability of intelligence to me connotes a flight back to mediocrity and a total lack of control. High heritability in contrast allows one to reclaim control, because you choose your spouse and you have a sense of their realized phenotype. Obviously this is conditional on where you stand on the distribution. So I emphasize the “I.” But many people at the higher end of the IQ distribution seem to want lower heritability, because they perceive that they can control outcomes through manipulation of environment. I’m not confident of this at all. Sometimes flighty academic abstractions can have real consequences in the choices we make in this world. This is one.

• Category: Science • Tags: IQ 

In the annals of “good GATTACA”, Rape suspect indicted with cutting-edge DNA testing:

A Dedham man freed earlier this year while awaiting trial on charges that he raped and robbed two women in Boston in 2004 has been re-indicted in the case, after cutting-edge DNA testing pointed to him as a suspect and ruled out his identical twin brother, according to authorities.

“To the best of my knowledge, this is the first time that any prosecutor’s office in America has attempted to use this [DNA testing] technique in court,” said Suffolk District Attorney Daniel F. Conley on Wednesday.

The suspect has an identical twin. This naturally results in reasonable doubt if you use standard genomic technology, which lacks the precision to discern any differences to a high degree of confidence when the sequences are so similar. But a very small number of mutations are unique to a given twin. To pull these needles out of the haystack you need powerful genomic technology. The prosecutors paid $100,000 dollars and had to delay the trial. But it seems that it was worth it. This level of sequencing power will not be needed in most cases in the future, but, it does make it so that legal dramas which hinge around the identity of a perp where the suspect has an identical twin will be the cause of less tension.

• Category: Race/Ethnicity • Tags: Sequencing 

Dienekes has posted some abstracts. I’ll be there.

• Category: Miscellaneous • Tags: ASHG 2014 

Vox has a piece on genetic testing and what it may unravel. One portion is cautionary:

That’s when she discovered Schwartzman. And her life changed. Afraid to ask her mother about him, she went instead to her mother’s best friend for answers. The friend confirmed that Schwartzman was probably the son Pearl’s mom had given up years ago.

“You can’t know what you’re going to find. It isn’t all good stuff. It’s not all happy stuff. And maybe some secrets are better left secrets.”

At first, it was “fantasy land,” Pearl said. “I found a brother. On his part, he found his biological family.” She was happy for Schwartzman, for his relief. “I felt an immediate kinship and connection with him,” she said. “We look similar. We have similar movements.”

Now, three years after the reunion, her opinion about the experience has changed.

“I suddenly had to rewrite my own family history, which is a shock,” Pearl said. “It did not make sense in terms of all the stories I had grown up with, in terms of what my life was. It did not include [my mother] getting pregnant, having a kid, giving it up for adoption.”

“This was my mother’s secret,” she said.

“My mother used to say, ‘Be careful what you wish for.’ [With 23andMe,] you can’t know what you’re going to find. It isn’t all good stuff. It’s not all happy stuff. And maybe some secrets are better left secrets.”

51dsZnatlbL._SY344_BO1,204,203,200_ My attitude about these issues about parental privacy in relation to adopted children is that the children weren’t asked to be born, they didn’t give consent. You give up a lot of rights when you make some decisions as an adult. Sometimes those rights you give up are precious. Sometimes it isn’t fair (consider a situation where a person who opposes abortion is raped, and so carries the baby to term). I agree that these are complex issues, and they need to aired out. But my moral stance is to first and foremost to look at the world through the eyes of future generations, who didn’t ask to be born into this world, and ask what would they want? Think about the children! It’s cliche, but it has a lot of truth to it. Some adopted children don’t want to know about their past. From what I have seen most do want to know more than they do, at least to an extent. Being a kid is hard enough.

More broadly, light is good. I’m not a Whig about progress, but both the norms and arc of Western history so far have been toward greater openness and candor. David Brin is a great science fiction author, but 50 years from now I suspect he’ll be remembered for writing The Transparent Society. It was interesting when it came out. Today it is incredibly relevant.

• Category: Science • Tags: Ethics 

Common genetic variants associated with cognitive performance identified using the proxy-phenotype method:

We identify several common genetic variants associated with cognitive performance using a two-stage approach: we conduct a genome-wide association study of educational attainment to generate a set of candidates, and then we estimate the association of these variants with cognitive performance. In older Americans, we find that these variants are jointly associated with cognitive health. Bioinformatics analyses implicate a set of genes that is associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. In addition to the substantive contribution, this work also serves to show a proxy-phenotype approach to discovering common genetic variants that is likely to be useful for many phenotypes of interest to social scientists (such as personality traits).

Ewen Callaway has a write up in Nature. The issue here is that it’s been evident for the past 10 years or so intelligence variation is not due to alleles segregating at high frequencies with at least modest effects, so they’re hard to pick up in association studies (contrast with pigmentation, which is mostly controlled by a number of loci on the order of 10). Some, such as Kevin Mitchell, don’t think that common variants are the way to go, period. Common as in variants which are found across the population, even if their effect on the trait is very small. This group disagrees. One of the authors, Peter Visscher, has written up his own view of this line of research, Intelligence inheritance – three genes that add to your IQ score:

This study of normal variation in cognitive performance confirms that there is no gene with a large effect on this trait. There is no “gene for intelligence” – instead, cognitive performance is likely to be influenced by thousands of genes, each having a small effect.

While the individual effect of the genetic variants are extremely small, their identification may lead to knowledge of the biological pathways involved in cognitive performance and cognitive ageing. This insight may eventually lead us into a better understanding of the mechanism involves in memory loss and dementia.

Finally, because individual gene effects are small, an implication of the study is that even larger studies, for example on millions of people, will lead to the discovery of many more gene variants.

In sum, because intelligence is at least moderately heritable, but the causal variants are so diffuse and numerous, the best bet for having a smart child is picking a spouse with a deviated phenotype. Look for smart people to marry….

• Category: Science • Tags: IQ 
Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at http://www.razib.com"