Sunday, August 20, 2017

Ninety-nine genetic loci influencing general cognitive function

The paper below has something like 200 authors from over 100 institutions worldwide.

Many people claimed just a few years ago (or more recently!) that results like this were impossible. Will they admit their mistake?

In Scientific Consensus on Cognitive Ability? I described the current consensus among experts as follows.
0. Intelligence is (at least crudely) measurable
1. Intelligence is highly heritable (much of the variance is determined by DNA)
2. Intelligence is highly polygenic (controlled by many genetic variants, each of small effect)
3. Intelligence is going to be deciphered at the molecular level, in the near future, by genomic studies with very large sample size
See figures below for a summary of progress over the last six years. Note 4% of total variance = 1/25 and sqrt(1/25) = 1/5, so a predictor built from these variants would correlate ~0.2 with actual cognitive ability. There is still much more variance to be discovered with larger samples, of course.
Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)

General cognitive function is a prominent human trait associated with many important life outcomes including longevity. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360). We found 9,714 genome-wide significant SNPs in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ, ATXN1, MAPT, AUTS2, and P2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.


Chinese Social Media Notices US Cultural Revolution

The joke below is making the rounds on Chinese social media.

See Struggles at Yale and Baizuo = Libtard.

Also circulating on Chinese social media: A Report on the Cultural Revolution in the United States.

Yes, an entire country can go crazy for a decade...
Cultural Revolution (Wikipedia): The Cultural Revolution, formally the Great Proletarian Cultural Revolution, was a sociopolitical movement that took place in China from 1966 until 1976. Set into motion by Mao Zedong, then Chairman of the Communist Party of China, its stated goal was to preserve 'true' Communist ideology in the country by purging remnants of capitalist and traditional elements from Chinese society, and to re-impose Maoist thought as the dominant ideology within the Party. ...

The movement paralyzed China politically and negatively affected the country's economy and society to a significant degree. ...

Libraries full of historical and foreign texts were destroyed; books were burned. Temples, churches, mosques, monasteries, and cemeteries were closed down ...




The Bannon Channel


Rumor has it that Bannon will start a Breitbart TV channel to rival Fox News. Given the success of YouTube- / pod-casters like Joe Rogan (5 million downloads per episode), it's plausible this could be done with very modest capex (the channel could start out as pure streaming and only go to cable later). Billionaire Robert Mercer (Renaissance Technologies) is a likely backer.

(The headline above actually appeared on the front page of the Huffington Post when it was announced that Bannon would leave the White House. It was quickly replaced with the headline White Flight -- swing state voters and 2018 midterm election voters will not forget either headline, I predict.)

Bannon's new channel can denounce Richard Spencer, Nazis, KKK, etc. but still push economic nationalism and even mild white identity slogans like  white people have rights, too  or  everyone should be treated as an individual, based on merit ... (gee, that last one seems pretty principled... maybe they could add something catchy like the content of their character or something like that).

They can keep winning on a populist platform with just 4 messages:

1. Economic Nationalism
2. No foreign wars
3. Reform immigration
4. Stop PC excesses

Again, not really to the right of Fox, but just more consistent and less corporate GOP ("cuck") content. Tucker Carlson and Hannity could move to the new network without changing their schtick in the slightest.

Mercer would be smart to back this based entirely on financial ROI. There is massive pent-up demand: Trump got about half the popular vote, but currently no major media outlet is aligned with the views of his supporters.

Friday, August 18, 2017

Embryo Selection in China (Nature)


China’s embrace of embryo selection raises thorny questions (Nature)

Fertility centres are making a massive push to increase preimplantation genetic diagnosis in a bid to eradicate certain diseases.

... Early experiments are beginning to show how genome-editing technologies such as CRISPR might one day fix disease-causing mutations before embryos are implanted. But refining the techniques and getting regulatory approval will take years. PGD has already helped thousands of couples. And whereas the expansion of PGD around the world has generally been slow, in China, it is starting to explode.

... Genetic screening during pregnancy for chromosomal abnormalities linked to maternal age has taken off throughout the country, and many see this as a precursor to wider adoption of PGD.

Although Chinese fertility doctors were late to the game in adopting the procedure, they have been pursuing a more aggressive, comprehensive and systematic path towards its use there than anywhere else. The country’s central government, known for its long-term thinking, has over the past decade stepped up efforts to bring high-quality health care to the people, and its current 5-year plan has made reproductive medicine, including PGD, a priority ...

Comprehensive figures are difficult to come by, but estimates from leading PGD providers show that China’s use of the technique already outpaces that in the United States, and it is growing up to five times faster.

... there are concerns about the push to select for non-disease-related traits, such as intelligence or athletic ability. The ever-present spectre of eugenics lurks in the shadows. But in China, although these concerns are considered, most thoughts are focused on the benefits of the procedures.

... And the centres with licences to do PGD have created a buzz in their race to claim firsts with the technology. In 2015, CITIC-Xiangya boasted China’s first “cancer-free baby”. The boy’s parents had terminated a prior pregnancy after genetic testing showed the presence of retinoblastoma, a cancer that forms in the eyes during early development and often leads to blindness. In their next try, the couple used PGD to ensure that the gene variant that causes retinoblastoma wasn’t present. Other groups have helped couples to avoid passing on a slew of conditions: short-rib-polydactyly syndrome, Brittle-bone disease, Huntington’s disease, polycystic kidney disease and deafness, among others. ...

Joe Leigh Simpson, a medical geneticist at Florida International University in Miami, and former president of the Preimplantation Genetic Diagnosis International Society, is impressed by the quality and size of the Chinese fertility clinics. They “are superb and have gigantic units. They came out of nowhere in just 2 or 3 years,” he says. ...

People in China seem more likely to feel an obligation to bear the healthiest child possible than to protect an embryo. The Chinese appetite for using genetic technology to ensure healthy births can be seen in the rapid rise of pregnancy testing for Down’s syndrome and other chromosomal abnormalities. Since Shenzhen-based BGI introduced a test for Down’s syndrome in 2013, it has sold more than 2 million kits; half of those sales were in the past year.

... The Chinese word for eugenics, yousheng, is used explicitly as a positive in almost all conversations about PGD. Yousheng is about giving birth to children of better quality. Not smoking during pregnancy is also part of yousheng. ...
优生学 加油!

Wednesday, August 16, 2017

Meet the Bot: OpenAI and Dota 2



OpenAI has created a Dota 2 bot that plays at the level of human professionals. Humans can look forward to coexistence with increasingly clever AIs in both virtual and real world settings. See also Robots taking our jobs.
OpenAI: Dota 1v1 is a complex game with hidden information. Agents must learn to plan, attack, trick, and deceive their opponents. The correlation between player skill and actions-per-minute is not strong, and in fact, our AI’s actions-per-minute are comparable to that of an average human player.

Success in Dota requires players to develop intuitions about their opponents and plan accordingly. In the above video you can see that our bot has learned — entirely via self-play — to predict where other players will move, to improvise in response to unfamiliar situations, and how to influence the other player’s allied units to help it succeed.
About the game ("Defense of the Ancient").
Wikipedia: Dota 2 is played in matches between two teams of five players, with each team occupying and defending their own separate base on the map. Each of the ten players independently controls a powerful character, known as a "hero", who all have unique abilities and styles of play. During a match, a player and their team collects experience points and items for their heroes in order to fight through the opposing team's heroes and other defenses. A team wins by being the first to destroy a large structure located in the opposing team's base, called the "Ancient".
Related: this is a nice recent interview with Demis Hassabis of Deep Mind. He talks a bit about Go innovation resulting from AlphaGo.

Monday, August 14, 2017

Estimation of genetic architecture for complex traits using GWAS data

These authors extrapolate from existing data to predict sample sizes needed to identify SNPs which explain a large portion of heritability in a variety of traits. For cognitive ability (see red curves in figure below), they predict sample sizes of ~million individuals will suffice.

See also More Shock and Awe: James Lee and SSGAC in Oslo, 600 SNP hits.
Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits and implications for the future

Yan Zhang, Guanghao Qi, Ju-Hyun Park, Nilanjan Chatterjee (Johns Hopkins University)

Summary-level statistics from genome-wide association studies are now widely used to estimate heritability and co-heritability of traits using the popular linkage-disequilibrium-score (LD-score) regression method. We develop a likelihood-based approach for analyzing summary-level statistics and external LD information to estimate common variants effect-size distributions, characterized by proportion of underlying susceptibility SNPs and a flexible normal-mixture model for their effects. Analysis of summary-level results across 32 GWAS reveals that while all traits are highly polygenic, there is wide diversity in the degrees of polygenicity. The effect-size distributions for susceptibility SNPs could be adequately modeled by a single normal distribution for traits related to mental health and ability and by a mixture of two normal distributions for all other traits. Among quantitative traits, we predict the sample sizes needed to identify SNPs which explain 80% of GWAS heritability to be between 300K-500K for some of the early growth traits, between 1-2 million for some anthropometric and cholesterol traits and multiple millions for body mass index and some others. The corresponding predictions for disease traits are between 200K-400K for inflammatory bowel diseases, close to one million for a variety of adult onset chronic diseases and between 1-2 million for psychiatric diseases.


This figure shows predicted effect size distributions for a number of quantitative traits. You can see that height and intelligence are somewhat different, but not in any fundamental sense.

Thursday, August 10, 2017

Meanwhile, down on the Farm


The Spring 2017 issue of the Stanford Medical School magazine has a special theme: Sex, Gender, and Medicine. I recommend the article excerpted below to journalists covering the Google Manifesto / James Damore firing. After reading it, they can decide for themselves whether his memo is based on established neuroscience or bro-pseudoscience.

Perhaps top Google executives will want to head down the road to Stanford for a refresher course in reality.

Stanford Neuroscience Professor Nirao Shah and Diane Halpern, past president of the American Psychological Association, would both make excellent expert witnesses in the Trial of the Century.
Two minds: The cognitive differences between men and women

... Nirao Shah decided in 1998 to study sex-based differences in the brain ... “I wanted to find and explore neural circuits that regulate specific behaviors,” says Shah, then a newly minted Caltech PhD who was beginning a postdoctoral fellowship at Columbia. So, he zeroed in on sex-associated behavioral differences in mating, parenting and aggression.

“These behaviors are essential for survival and propagation,” says Shah, MD, PhD, now a Stanford professor of psychiatry and behavioral sciences and of neurobiology. “They’re innate rather than learned — at least in animals — so the circuitry involved ought to be developmentally hard-wired into the brain. These circuits should differ depending on which sex you’re looking at.”

His plan was to learn what he could about the activity of genes tied to behaviors that differ between the sexes, then use that knowledge to help identify the neuronal circuits — clusters of nerve cells in close communication with one another — underlying those behaviors.

At the time, this was not a universally popular idea. The neuroscience community had largely considered any observed sex-associated differences in cognition and behavior in humans to be due to the effects of cultural influences. Animal researchers, for their part, seldom even bothered to use female rodents in their experiments, figuring that the cyclical variations in their reproductive hormones would introduce confounding variability into the search for fundamental neurological insights.

But over the past 15 years or so, there’s been a sea change as new technologies have generated a growing pile of evidence that there are inherent differences in how men’s and women’s brains are wired and how they work.

... There was too much data pointing to the biological basis of sex-based cognitive differences to ignore, Halpern says. For one thing, the animal-research findings resonated with sex-based differences ascribed to people. These findings continue to accrue. In a study of 34 rhesus monkeys, for example, males strongly preferred toys with wheels over plush toys, whereas females found plush toys likable. It would be tough to argue that the monkeys’ parents bought them sex-typed toys or that simian society encourages its male offspring to play more with trucks. A much more recent study established that boys and girls 9 to 17 months old — an age when children show few if any signs of recognizing either their own or other children’s sex — nonetheless show marked differences in their preference for stereotypically male versus stereotypically female toys.

Halpern and others have cataloged plenty of human behavioral differences. “These findings have all been replicated,” she says.

... “You see sex differences in spatial-visualization ability in 2- and 3-month-old infants,” Halpern says. Infant girls respond more readily to faces and begin talking earlier. Boys react earlier in infancy to experimentally induced perceptual discrepancies in their visual environment. In adulthood, women remain more oriented to faces, men to things.

All these measured differences are averages derived from pooling widely varying individual results. While statistically significant, the differences tend not to be gigantic. They are most noticeable at the extremes of a bell curve, rather than in the middle, where most people cluster. ...


See also Gender differences in preferences, choices, and outcomes: SMPY longitudinal study. These preference asymmetries are not necessarily determined by biology. They could be entirely due to societal influences. But nevertheless, they characterize the pool of human capital from which Google is trying to hire.
The recent SMPY paper below describes a group of mathematically gifted (top 1% ability) individuals who have been followed for 40 years. This is precisely the pool from which one would hope to draw STEM and technological leadership talent. There are 1037 men and 613 women in the study.

The figures show significant gender differences in life and career preferences, which affect choices and outcomes even after ability is controlled for. (Click for larger versions.) According to the results, SMPY men are more concerned with money, prestige, success, creating or inventing something with impact, etc. SMPY women prefer time and work flexibility, want to give back to the community, and are less comfortable advocating unpopular ideas. Some of these asymmetries are at the 0.5 SD level or greater. Here are three survey items with a ~ 0.4 SD or more asymmetry:

# Society should invest in my ideas because they are more important than those of other people.

# Discomforting others does not deter me from stating the facts.

# Receiving criticism from others does not inhibit me from expressing my thoughts.

I would guess that Silicon Valley entrepreneurs and leading technologists are typically about +2 SD on each of these items! One can directly estimate M/F ratios from these parameters ...
For example, if a typical male SV entrepreneur / tech leader is roughly +2SD on these traits whereas a female is +2.5SD, the population fraction would be 3:1 or 4:1 larger for males. This doesn't mean that the females who are > +2.5SD (in the female population) are ill-suited to the role (they may be as good as the men), just that there are fewer of them in the general population. I was shocked to see that even top Google leadership didn't understand this point that Damore tried to make in his memo.

A 6ft3 Asian-American guard (Jeremy Lin) might be just as good as other guards in the NBA, but the fraction of Asian-American males who are 6ft3 is smaller than for other groups, like African-Americans. Even if there were no discrimination against Asian players, you'd expect to see fewer (relative to base population) in the NBA due to the average height difference.


Behold the Brogrammer: James Damore (Bloomberg video)



Watch a few minutes of this Bloomberg interview and I think you'll agree he's both sincere and well-meaning, if a bit naive about the buzzsaw he has stepped into. Definitely not a brogrammer.

He reminds me of Richard Hendricks of the HBO show Silicon Valley.


See also Damore vs Google: Trial of the Century? and In the matter of James Damore, ex-Googler

Damore vs Google: Trial of the Century?


In his memo, James Damore asserts that Google is engaged in illegal discriminatory practices as part of its efforts to increase diversity. (See earlier post, In the matter of James Damore, ex-Googler.)

The image below is from the actual memo. Does Damore sound like a sexist brogrammer Neanderthal?


OKRs = Objectives and Key Results. Damore is pointing out that pro-diversity objectives may incentivize managers to discriminate by gender or race in hiring and promotion.

According to Margot Cleveland (attorney who teaches labor law at Notre Dame):
The Federalist: ... Damore wrote “Google has created several discriminatory practices.” This reads of a classic case of opposition to an unlawful employment practice. (Under the case law, the practice need not actually be illegal if the employee reasonably believed it discriminatory.)

This passage may well be Google’s undoing. Damore can present a prima facie case of illegal retaliation: he engaged in protected activity by opposing several discriminatory practices, and was fired from his job. The close temporal nexus creates an inference that Google fired him because of his opposition to illegal discrimination.

... Google will counter that it fired him not because of his opposition but because of the gender stereotypes he included in the memo.
But of course the Google Brain was simultaneously using these "stereotypes" = correlations as its core revenue driver:


Professor Cleveland concludes:
... Once before a jury, Google will be hard-pressed to justify Damore’s firing because the jury will be force-fed the actual words Damore wrote, not the press’ hysterical gloss. In this regard, Google was in a no-win situation: Once the Neanderthal narrative formed, Google had no real choice but to fire Damore—which doesn’t make it right or, as Google is likely to find out soon, legal. In the meantime, the rest of the country will be treated to a nice civics refresher course and a deep-dive into federal employment and labor law.
Not to mention a deep-dive into the science of statistical / distributional group differences!

Bloomberg video interview with Damore.

Tuesday, August 08, 2017

In the matter of James Damore, ex-Googler


James Damore, Harvard PhD* in Systems Biology, and (until last week) an engineer at Google, was fired for writing this memo: Google’s Ideological Echo Chamber, which dares to display the figure above.

Here is Damore's brief summary of his memo (which contains many citations to original scientific research), and the conclusion:
Google’s political bias has equated the freedom from offense with psychological safety, but shaming into silence is the antithesis of psychological safety.
● This silencing has created an ideological echo chamber where some ideas are too sacred to be honestly discussed.
● The lack of discussion fosters the most extreme and authoritarian elements of this ideology.
○ Extreme: all disparities in representation are due to oppression
○ Authoritarian: we should discriminate to correct for this oppression
● Differences in distributions of traits between men and women may in part explain why we don't have 50% representation of women in tech and leadership.
● Discrimination to reach equal representation is unfair, divisive, and bad for business.


I hope it’s clear that I’m not saying that diversity is bad, that Google or society is 100% fair, that we shouldn’t try to correct for existing biases, or that minorities have the same experience of those in the majority. My larger point is that we have an intolerance for ideas and evidence that don’t fit a certain ideology. I’m also not saying that we should restrict people to certain gender roles; I’m advocating for quite the opposite: treat people as individuals, not as just another member of their group (tribalism).
This actual excerpt is of course very different from the heavily biased (mendacious) characterizations of the memo in the (lying) media. Perhaps that should make you wonder about the reliability of mainstream accounts concerning this matter.

Damore correctly anticipated his own demise! CEO Sundar Pichai's company-wide message seems to ban almost all scientific discussion of statistical or distributional group differences, on threat of termination:
This has been a very difficult time. I wanted to provide an update on the memo that was circulated over this past week.

First, let me say that we strongly support the right of Googlers to express themselves, and much of what was in that memo is fair to debate, regardless of whether a vast majority of Googlers disagree with it. However, portions of the memo violate our Code of Conduct and cross the line by advancing harmful gender stereotypes in our workplace. Our job is to build great products for users that make a difference in their lives. To suggest a group of our colleagues have traits that make them less biologically suited to that work is offensive and not OK. It is contrary to our basic values and our Code of Conduct, which expects “each Googler to do their utmost to create a workplace culture that is free of harassment, intimidation, bias and unlawful discrimination.”

The memo has clearly impacted our co-workers, some of whom are hurting and feel judged based on their gender. Our co-workers shouldn’t have to worry that each time they open their mouths to speak in a meeting, they have to prove that they are not like the memo states, being “agreeable” rather than “assertive,” showing a “lower stress tolerance,” or being “neurotic.”

At the same time, there are co-workers who are questioning whether they can safely express their views in the workplace (especially those with a minority viewpoint). They too feel under threat, and that is also not OK. People must feel free to express dissent. So to be clear again, many points raised in the memo—such as the portions criticizing Google’s trainings, questioning the role of ideology in the workplace, and debating whether programs for women and underserved groups are sufficiently open to all—are important topics. The author had a right to express their views on those topics—we encourage an environment in which people can do this and it remains our policy to not take action against anyone for prompting these discussions. ...
Larry Summers was fired from the Harvard presidency (at least in part) for pointing out (correctly, it seems) that males exhibit higher variance in performance on cognitive tests (more very low- and high-scoring men than women per capita). His detractors justified the termination due to his highly public and symbolic role as the leader of the institution. In contrast, Damore was simply an engineer (with a background in computational biology) expressing his opinion on some basic scientific questions still under active investigation by researchers all over the world. His firing has to be regarded as scary authoritarian policing of thought.

See also Bounded Cognition, Gender differences in preferences, choices, and outcomes, 2:1 faculty preference for women on STEM tenure track (PNAS), and Gender trouble in the valley.

A literature review at Slate Star Codex.

If I worked at Google would this blog post get me fired?


Note Added:

* Damore may be ABD (left Harvard before completing his dissertation) rather than a PhD.

Damore is going to fight Google in court (NYTimes):
Mr. Damore, who worked on infrastructure for Google’s search product, said he believed that the company’s actions were illegal and that he would “likely be pursuing legal action.”

“I have a legal right to express my concerns about the terms and conditions of my working environment and to bring up potentially illegal behavior, which is what my document does,” Mr. Damore said.

Before being fired, Mr. Damore said, he had submitted a complaint to the National Labor Relations Board claiming that Google’s upper management was “misrepresenting and shaming me in order to silence my complaints.” He added that it was “illegal to retaliate” against an N.L.R.B. charge.
According to The Federalist, Damore has a case. This trial of the century might expose large numbers of people to the ideas in his memo...

Bloomberg video interview with Damore.

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