# Genes and Intelligence

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Assuming that intelligence has a genetic component,

• do we know which genes contribute to it?

and, if so,

• can we predict intelligence from genomic analysis?

### A few words on genomic prediction

No complex trait is 100% heritable, hence no prediction based entirely on DNA would ever be perfect. With that said, predictive genomics is progressing at a quite amazing rate right now. So while predictions can be nowhere near perfect, it is getting possible to make DNA predictions that correlate substantially with observed values.

The genes that correlate with phenotypic differences are found using genome-wide association studies (GWAS). The total effects are then aggregated up to what is called a polygenic score.

### A success story -- Height

Height is highly heritable, meaning that much of the phenotypic variance (although not 100%) is due to genetic differences. Height is also highly polygenic -- it's a trait influenced by many genes, each of small effect.

Many variants that correlate with height have now been found. Polygenic scores of height correlate higher than ~0.60 with observed height. DNA predictions are generally within a few centimeters of true height (Lello, Avery, Tellier, Vazquez, de los Campos, Hsu, 2018). According to an interview with Stephen Hsu, one of the authors of this paper and co-founder of the company Genomic Prediction, they can correctly predict the height ordering of siblings within the same family 80-90% of the time (source). So based purely on DNA, can we say which of two siblings are going to be taller than the other? Not perfectly, but with decent reliably, yes.

This is about as good as predictions of complex traits can be based on current methods. There are a few principal reasons that correlations are not higher (even though it is quite impressive already in its own right). First, as I said, complex traits are not 100% heritable and therefore predictions are not expected to ever be perfect. Second, current GWAS are typically based on SNPs which are common gene variants. Rarer gene variants are expected to contribute to the variance and their effects are still needed to be uncovered. Third, only additive effects are taken into account, not gene-by-gene interactions.

### Genetic IQ Prediction?

IQ, like height, is a heritable trait and is highly polygenic.

There are several approaches to finding gene variants correlated with IQ, however they can broadly be categorized into two. The most obvious approach is to simply give people intelligence tests and get their DNA. The problem with this is that it is difficult to get large samples with good intelligence tests. When this approach is used, usually a very short (say, 2 min) intelligence test is used. The second approach is to use a proxy phenotype. With this approach, the variable years of educational attainment has been used to good success, and has been shown to have a high genetic correlation with intelligence ($$r_g approx 0.7$$).

Many variants that are associated with intelligence or educational attainment have been found, see e.g. (Lee et al, 2018; Savage et al, 2018). While many variants are known, IQ is not as well understood as height, and current SNP predictors correlate about ~0.3 with observed IQ (See e.g. Allegrini et al, 2018). This correlation is bound to increase in the coming few years.

### Further Information

If you want a simple introduction to what can be read from the genome so far, there is a TED talk on this subject, TED2016: How to read a genome and build a human being. Although, major improvements have already been made in the years since 2016. For anyone that is more interested in the mathematical techniques used for prediction and the underlying theory, I recommend this talk by Stephen Hsu if you're further interested in genomic prediction of complex traits. I also recommend reading this review by Robert Plomin and Sophie von Stumm to get an easily understandable overview of the current state of knowledge on the subject.

### References

Lello, Avery, Tellier, Vazquez, de los Campus, Hsu (2018). Accurate Genomic Prediction of Human Height. DOI: https://doi.org/10.1534/genetics.118.301267

Marty Nemko (2018). The Future of In-Vitro Fertilization and Gene Editing. Psychology Today Link.

Lee,… , Cesarini (2018). Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. DOI: https://doi.org/10.1038/s41588-018-0147-3

Savage,… , Posthuma (2018). Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. DOI: https://doi.org/10.1038/s41588-018-0152-6

Allegrini, Selzam, Rimfeld, von Stumm, Pingault, Plomin (2018). Genomic prediction of cognitive traits in childhood and adolescence. DOI: https://doi.org/10.1101/418210

Sabatini (2016). How to read a genome and build a human being. TED2016 Link to Talk.

Plomin, von Stumm (2018). The new genetics of intelligence. DOI: https://doi.org/10.1038/nrg.2017.104

No, because the trait you describe does not exist

Your question betrays a common misunderstanding of how genetics and the environment interact in order to produce complex phenotypes. In fact, every biological trait is 100% genetic and 100% environmental. Don't believe me? Try teaching algebra to your cat, or see what height someone is after you've dropped them into the sun.

The only sense in which you have an "IQ you were born with" is the measurable IQ of a newborn child which I'm guessing this comes out as 0. Instead your IQ is a result of continuous interaction between genes and environment. You can say that at the end of process, across the population, 70% (say) of observed variation is explicable by genetic variation but this does not mean that you got 70 points of IQ from your genes and 30 points from the environment. The whole score is attributable to an interaction between the two. There is no "null" environment in which you would observe pure genetics, nor does it follow that increasing the range of environments encountered across your sample will increase the proportion of variation explicable by the environment. A gene that has no effect on IQ in one environment may have a marked effect in a different environment and you'd only discover this by varying the environment so both are encountered.

So, there is no trait "genetic IQ" to predict from someone's DNA, even if we had perfect knowledge of the link between genes and intelligence. Which we don't.

IQ typically has a relatively high heritability (see this post). Please have a look at this post to understand the concept of heritability.

In order to know what loci (QTL as the trait of interest is quantitative) are associated with a specific trait of interest, one must perform a GWAS The studies listed in the first pots linked above do not involve GWAS but only some kind of parent-offspring regression or twin studies to estimate heritability. From these studies, one cannot infer anything about a person's IQ from its genome.

GWAS studies on IQ do exist though (reviewed in Pfiffer 2015). It would be possible from one to make predictions and compute confidence intervals as well of someone's intelligence based on their genome, yes. I doubt anyone ever wrote such algorithm though. Without having such algorithm in front of one's eyes, it is impossible to tell, whether the confidence intervals are going to be very wide or very narrow though.

IQ is pretty much like muscle strength, in the sense that you may have the right combination of genes that would give you extra strong muscles but the environmental factors do play an essential role as well.

Nutrition, training etc will have a profound effect on the development of your muscles. You cannot predict the effect a priori.

For IQ, it is the same thing. On one extreme you may have genetically-linked developmental diseases, physically impairing the normal brain functions, i/e/ negatively affects your IQ. In most of the cases however, the effects of genetics on IQ is shadowed by the actual "brain training" you get during your life, by nutrition, and by other environmental factors.

So, yes, IQ is influenced by the underlying genetics.

Yes, in some extreme cases you can predict a very strong detrimental effect of some genes/mutations on the IQ.

For most of the cases, it's very hard to predict and genetics alone would not be enough to do so.

## The biology of intelligence?

The idea that there is a biological basis for intelligence in people has been translated into two beliefs about IQ tests: first, that measured IQ is genetically determined and that differences in IQ between different groups are partly or largely caused by genetic differences between them secondly, that IQ reflects some presumed fundamental property of the brain such as efficiency or speed of neural transmission, that can be measured by recording evoked potentials or by the speed with which a person performs some very simple task. Measured IQ may well have a significant heritable component, but there is very little evidence that average differences in IQ between, say, different ethnic groups are genetic in origin. In Great Britain, moreover, differences in IQ between white, West Indian, Indian or Pakistani children are closely correlated with differences in their social circumstances. It should be stressed, however, that there is equally little evidence that IQ tests significantly underestimate the academic attainments of children from ethnic minorities or that such children fall progressively further behind as they go through school. The search for simple, physiological or behavioural correlates of IQ has met with no more than modest success. Recent reports of highly significant correlations between IQ and measures of evoked potentials have not always been replicated and the past history of failures of replication in this general area counsels caution. Reports of very high (greater than 0.60) correlations between IQ and measures of timed performance have not been substantiated and can usually be attributed to the inclusion of disproportionate numbers of retarded subjects in the samples. There is quite good evidence of moderate correlations (in the range 0.20 to 0.40) with those measures, but it is not even clear how they should be interpreted. One possibility is that they reflect differences in concentration or sustained attention. If we want higher correlations with IQ we will probably need to look to more sophisticated tasks.

## Large study uncovers genes linked to intelligence

Genes controlling how our nervous system develops are linked to intelligence. Credit: Evgeny Atamanenko

Exactly what constitutes intelligence, and to what extent it is genetic, are some of the most controversial questions in science. But now a new study of nearly 80,000 people, published in Nature Genetics, has managed to identify a number of genes that seem to be involved in intelligence.

According to a dictionary definition, intelligence is "the ability to learn, understand or deal with new situations" or "the ability to apply knowledge to manipulate one's environment or to think abstractly".

This is obviously quite broad. Indeed, even animals display a number of different forms of intelligence, typically critical for survival. These range from reaching or gathering sources of food and escaping predators to the sharing of duties within a group (such as in ant communities). Elephants or monkeys also possess forms of empathy and care, which strengthen their relationships and chances to survive.

Human intelligence started out as "reactive", enabling us to find solutions to the challenges of nature. But it later became "proactive", so that we could use the resources of nature to develop preventive measures aimed at solving problems. Ultimately, what makes human intelligence different from that of other animals is our ability to shape the environment, for example through farming. This became possible as we developed communities and started delegating tasks on the basis of talents. When the acute problem of survival was controlled, we could dedicate our intelligence to the development of arts or other higher skills.

There are many factors that enable us to shape and nurture our intelligence – ranging from access to resources and information to skills acquired through experience and repetition. But, like with most human traits, there is also a genetic basis.

The method used to measure intelligence in the new study was the so-called "g-factor" – a measure of analytical intelligence. Although it might appear reductive to catalogue all types of intelligence through a single test, the g-factor is often used in scientific research as being among the most unbiased methods. The authors looked at such scores in 78,000 people of European descent to search for genetic factors and genes that potentially influence human intelligence.

They carried out a genome-wide association study (GWAS). This assesses connections between a trait and a multitude of DNA markers called single-nucleotide polymorphisms, or SNPs, which might determine an individual's likelihood to develop a specific trait. The test enabled the researchers to identify 336 significant SNPs.

Generally, the vast majority of significant SNPs that result in this way fall in non-coding regions of the DNA. In other words, they indicate portions of the DNA that may regulate gene expression even though the actual regulated gene is unknown. This makes the SNPs from GWAS hard to interpret. So the authors then complemented their analysis with a so called genome-wide gene association analysis (or GWGAS), which calculates the effect of multiple SNPs within genes and can identify actual associated genes. They then combined both kinds of study to strengthen their confidence in naming the genes associated with intelligence.

This work led to isolating 52 candidate genes linked to intelligence. Although 12 of these had been previously associated with "intelligence", the study needs to be replicated in future studies.

The researchers discovered that the genes that were the strongest linked to intelligence are ones involved in pathways that play a part in the regulation of the nervous system's development and apoptosis (a normal form of cell death that is needed in development). The most significant SNP was found within FOXO3, a gene involved in insulin signalling that might trigger apoptosis. The strongest associated gene was CSE1L, a gene involved in apoptosis and cell proliferation.

Does this all mean that intelligence in humans depends on the molecular mechanisms that support the development and preservation of the nervous system throughout an person's lifespan? It's possible.

And is it possible to explain intelligence through genetics? This paper suggests it is. Nevertheless, it might be warranted to consider that intelligence is a very complex trait and even if genetics did play a role, environmental factors such as education, healthy living, access to higher education, exposure to stimulating circumstances or environments might play an equally or even stronger role in nurturing and shaping intelligence.

It is also worth considering that the meaning of "intelligence" rather falls within a grey area. There might be different types of intelligence or even intelligence might be interpreted differently: in which category would for example a genius physicist – unable to remember their way home (Albert Einstein) – fall? Selective intelligence? Mozart nearly failed his admission tests to Philharmonic Academy in Bologna because his genius was too wide and innovative to be assessed by rigid tests. Is that another form of selective intelligence? And if so, what's the genetic basis of this kind of intelligence?

Studies like this are extremely interesting and they do show we are starting to scratch the surface of what the biological basis of intelligence really is.

## Biological Intelligence

Biological intelligence is a new concept that’s nearly four billion years old. How does your body create and use knowledge? Biological intelligence teaches your body to teach itself. Just like you educate your brain, you can teach your body.

Lots of people have heard about artificial intelligence, or AI. But why haven’t you heard about biological intelligence, or BI? Because most of biological intelligence is quiet and unconscious. You see your hair grow. You don’t see your body learn.

Take immunity, your ability to fight infection and cancer. Your ability to fight off the flu is not something you know about—unless you get sick. Look at cancer. We probably form dozens of tiny cancers each and every day. But we destroy almost all of them so effectively we never know. Biological intelligence engages all of immunity's remarkable tasks. One of the future tasks of biological intelligence is to teach the body to correctly recognize cancers that have been missed, then make the immune system go after them. Yet biological intelligence is much more than destroying viruses and tumors. Biological intelligence is the basic stuff that keeps you going. It teaches your body to do what it needs to do.

It’s so big, so important, it's useful to compare it with artificial intelligence, the stuff transforming our lives and economy:

1. Biological intelligence engages all the conscious and unconscious knowledge of a human being. That immense field stretches from genetics to culture to society and psychology. Much of it is hardly understood. Your mother’s arm that holds you in an embrace, the lover’s hand that gently touches your cheek, and the little gestures that tell you’re loved will prove hard work for robots.

2. Biological intelligence is connected to everything inside you—every information system you use. You have an immune system, a cardiovascular system, a hormonal system, a muscular system, dozens of interconnected systems. Unlike most robots, the body doesn’t do one thing at a time. It coordinates all the different information systems at the same moment. Can you presently conceptualize the systems that will have a robot laugh, cry, sing and dance, all while gauging the audience and telling a joke? Comedians do that. The size of your body’s information systems dwarf the complexity of the entire Internet. Our medical attempts to make ourselves not ill are generally far less impressive than the actions biological intelligence engages every moment to keep us healthy.

3. Biological intelligence has different goals than artificial intelligence. What is it for? In our case, the survival of our species. Biological intelligence is built to keep humanity going. Normally that includes you, and me, and everyone we know—but not always. Having genes for sickle cell may help a population survive malaria, but can really hurt you in places without it. Diabetes genes may keep us stay alive during famines, but otherwise can really mess up your life. Biological intelligence wants the species to survive—not just us.

4. Unlike the artificial intelligence you experience in glitching software, biological intelligence has survived almost everything thrown at it. It survived the asteroids that wiped out the dinosaurs. It survived volcanoes that scorched and burnt the earth for millions of years. It survived plagues and pestilence. Most of the species on the planet are gone. Billions of species have disappeared. We’re still here. Why? Because biological intelligence built us to survive.

5. So how does biological intelligence work? Here’s the real trick: biological intelligence is built on contingency and chance. Stephen Jay Gould and others pointed that out long ago. Not only do we have genetic information systems that survived asteroids. We’re built to survive comets, earthquakes, cataclysms and catastrophes that we’ve never seen—and that may never happen. Biological intelligence provides us genes and physiology that's built to survive stresses that do not yet exist and may never exist. Chance rules the world, and we are built to survive all that chance can throw at us. Think of new illnesses, like AIDS. When AIDS first hit it was terrifying. Yet many of us had inbuilt systems to keep it off, even before one effective drug was produced.

6. Unlike artificial intelligence, biological intelligence does not operate just within us, but over a huge ecosystem. That ecosystem is you. There are at least 40 trillion bacteria in your gut. They not only digest food, but now appear to change your mood, your ability to fight off infections, how cancer drugs work. There’s at least 10 times more non-human cells in your body than human ones. Biological intelligence rules them all.

So biological intelligence is big. It does amazing things. Because we haven’t thought of the body as intelligent and perpetually learning, we don’t even know what many of those capacities are. That’s the power of a system built on chance, a system created through billion of years of failures and triumphs.

But here’s the real take home: knowing that your body is intelligent can make you more intelligent. Because what you do is what you become. Every moment of life is a teaching moment. Every moment potentially gives you chances to make your body more capable, more intelligent, smarter. Everything you do teaches your body something new.

If you want to get smart, you need education. In school we teach our brains. Now we need to teach our bodies. Biological intelligence make you resilient, more capable, more able to produce and create, more capable to avoid and fight off disease. We need to teach our bodies to teach themselves.

The robots are advancing, at work and play. Artificial intelligence is getting smarter every day. So should you.

## Genes and Intelligence - Biology

By Diane Swanbrow
News Service

Environmental conditions are much more powerful than genetic influences in determining intelligence, social psychologist Richard Nisbett says.

Recent research in psychology, genetics and neuroscience, and new studies on the effectiveness of educational interventions, have shown that intelligence strongly is affected by environmental factors that have nothing to do with genes, Nisbett says. In new research, Nisbett analyzes a large number of such studies, showing how environment influences not just IQ as measured by standardized tests but also actual achievement.

"Believing that intelligence is under your control — and having parents who demand achievement — can do wonders," Nisbett writes in "Intelligence and How to Get It: Why Schools and Cultures Count," published Feb. 2 by W.W. Norton & Company Inc.

For example, the high academic and occupational attainment of Asians and Jews is not due to higher IQs, but to family values that emphasize accomplishment and intellectual attainment, and to cultures that emphasize hard work and persistence.

Likewise, genes play no role in race differences in IQ between blacks and Caucasians, Nisbett says. Class and race differences starting in early infancy combine with neighborhood, cultural and educational differences that widen this gap.

"We need intensive early childhood education for the poor, and home visits to teach parents how to encourage intellectual development," Nisbett writes. "Such efforts can produce huge immediate gains in IQ and enormous long-term gains in academic achievement and occupational attainment.

"Highly ambitious elementary, junior high and high school programs also can produce massive gains in academic achievement. And a variety of simple, cost-free interventions, including, most notably, simply convincing students that their intelligence is under their control to a substantial extent, can make a big difference to academic achievement."

The United States has fallen behind most of the developed world in its level of educational achievement, Nisbett points out, attributing this deficit to the large and widening gaps between socioeconomic classes in this country.

Being poor, he says, is linked with many environmental factors of a biological and social nature that lower IQ and academic achievement. These factors include poor nutrition, inferior medical care, a low rate of breast-feeding and parenting styles that are much less warm and supportive than those of higher socioeconomic status parents. Not only are many U.S. blacks afflicted with these problems, they also struggle with stereotypes and prejudice that intensify decreases in performance.

Nisbett singles out several educational intervention programs that have been shown to be effective in closing the racial and socioeconomic gap in school achievement. He also debunks the claims of success in other programs and techniques, including the No Child Left Behind Act.

## Hundreds of new genes may underlie intelligence—but also autism and depression

Being smart is a double-edged sword. Intelligent people appear to live longer, but many of the genes behind brilliance can also lead to autism, anxiety, and depression, according to two new massive genetic studies. The work also is one of the first to identify the specific cell types and genetic pathways tied to intelligence and mental health, potentially paving the way for new ways to improve education, or therapies to treat neurotic behavior.

The studies provide some of the first “hard evidence of the many genes and pathways” that work together in complex ways to build smart brains and keep them in balance, says geneticist Peter Visscher of the Queensland Brain Institute at The University of Queensland in Brisbane, Australia, who was not involved in the work.

Researchers have long known that people often inherit intelligence and some personality disorders from their parents. (Environmental factors such as education and stress also profoundly shape intelligence and mental health.) But geneticists have had trouble identifying more than a handful of genes associated with intelligence. Last year, researchers used new statistical methods that can detect strong associations between genes and specific traits to analyze health and genetic records in huge data sets. This led to the discovery of 52 genes linked to intelligence in 80,000 people.

Now, the same team has added almost 1000 genes to that list. Researchers led by geneticist Danielle Posthuma of Vrije University in Amsterdam scoured 14 databases of health and genetic records to identify 939 new genes associated with intelligence in 250,000 individuals. (The data sets measured intelligence with scores on tests of abilities such as mathematics, synonyms, and logic.) Many variants of genes associated with higher intelligence turned up in people who also lived longer and did not have Alzheimer’s disease, attention-deficit hyperactivity disorder, or schizophrenia, the team reports today in Nature Genetics , suggesting that intelligence protects against these disorders. On the downside, genes associated with intelligence correlated with a higher risk for autism.

In a separate study also published today in Nature Genetics , Posthuma and her colleagues identified 500 genes associated with neurotic traits, such as anxiety and depression, by searching the health and genetic records of 449,400 individuals in large databases, such as the UK Biobank, a repository of information on the genetics, health and wellbeing of 500,000 British volunteers, and 23andMe, a personal genomics company in Mountain View, California, with genetic and health data on 5 million customers. They also found that people who worried a lot had inherited different genes than those who were more likely to be depressed, suggesting that there are different underlying genetic pathways for those conditions.

In both studies, the researchers used a new statistical method called MAGMA to quickly search genetic data to identify specific types of cells and tissues where the genes were expressed. Many genes for intelligence were expressed in the “medium spiny neurons” which are part of the basal ganglia, clusters of neurons deep in the brain involved in learning, cognition, and emotion. The researchers also identified many potential targets for developing new pharmaceutical drugs.

“If you can understand the mechanisms at the cell level, you can also look at candidates for medication,” Posthuma says. The same is true for genes for intelligence, she says, which could offer clues to new ways to protect against Alzheimer’s and other disorders.

## New Theory: How Intelligence Works

Like memory, human intelligence is probably not confined to a single area in the brain, but is instead the result of multiple brain areas working in concert, a new review of research suggests.

The review by Richard Haier of the University of California , Irvine , and Rex Jung of the University of New Mexico proposes a new theory that identifies areas in the brain that work together to determine a person's intelligence.

"Genetic research has demonstrated that intelligence levels can be inherited, and since genes work through biology, there must be a biological basis for intelligence," Haier said.

The review of 37 imaging studies, detailed online in the journal Behavioral and Brain Sciences, suggests that intelligence is related not so much to brain size or a particular brain structure, but to how efficiently information travels through the brain.

"Our review of imaging studies identifies the stations along the routes intelligence information processing takes," Haier said. "Once we know where the stations are, we can study how they relate to intelligence."

The new theory might eventually lead to treatments for low IQ, the researchers say, or to ways of boosting the IQ of people with normal intelligence.

In their review, Haier and Jung compiled a list of all the brain areas previous neuroimaging studies had found to be related to intelligence, placing greater emphasis on those areas that appeared multiple times. The list they came up with suggests that most of the brain areas thought to play a role in intelligence are clustered in the frontal and parietal lobes. Furthermore, some of these areas area also related to attention and memory and to more complex functions such as language. The pair does not think this is a coincidence. In their Parieto-Frontal Integration Theory (P-FIT), they suggest that intelligence levels are based on how efficiently these brain areas communicate with one another.

Haier says the new theory sidesteps the sticky question of what intelligence is, something that scientists have yet to agree on. "In every single study that we reviewed, there was a different measure of intelligence," Haier said. "There's controversy about what is the best measure of intelligence. There's controversy over how broad or narrow the definition of intelligence should be. Our work really goes beyond those questions and basically says that irrespective of the definition of intelligence you use in neuroimaging studies, you find a similar result."

Earl Hunt, a neuroscientist at the University of Washington , who was not involved in the research, said the P-FIT model highlights the progress scientists have made in recent years toward understanding the biological basis of intelligence. "Twenty-five years ago researchers in the field were engaged in an unedifying discussion of the relation between skull sizes and intelligence test scores," Hunt said.

Building upon previous work

Haier and Jung were also behind other important intelligence-related studies. In 2004, they found that regions related to general intelligence are scattered throughout the brain and that the existence of a single "intelligence center" was unlikely.

And in a 2005 study, they found that while there is essentially no difference in general intelligence between the sexes, women have more white matter and men more gray matter. Gray matter represents information processing centers in the brain, and white matter links the centers together. The finding suggested that no single structure in the brain determines general intelligence and that different types of brain designs can produce equivalent intellectual performance.

Knowing what determines intelligence might lead to treatments for diseases of intelligence like mental retardation, Haier said.

"It would be important to now how intelligence works to determine if there's any way to treat low IQ," Haier told LiveScience. "If you can treat low IQ in mental retardation because you identify something wrong in the brain that's affecting intelligence, then that raises the question of whether you can raise IQ in people that don't necessarily have the brain injuries."

## Do genes affect our intelligence? The debate ‘is over’

Researchers are now becoming confident enough to claim that the information available from sequencing a person’s genome – the instructions encoded in our DNA that influence our physical and behavioural traits – can be used to make predictions about their potential to achieve academic success.

All too often genes are read as destiny. But in truth there’s rather little in your genetic make-up that fixes traits or behaviour with any clarity. There are some genetic diseases that particular gene mutations will give you if you’re unlucky enough to inherit them. But most traits (including diseases) that are influenced by genes manifest only as tendencies.

Partly this is because a lot of traits are influenced by many genes, interacting and correlating with one another in complex ways that are hard, perhaps impossible, to anticipate. But it’s also because genes are themselves influenced by environmental factors, which can cause them to be activated or suppressed.

The data both from twin studies and DNA analysis are unambiguous: intelligence is strongly heritable. Typically around 50 per cent of variations in intelligence between individuals can be ascribed to genes, although these gene-induced differences become markedly more apparent as we age. As [psychologist Stuart] Ritchie says: like it or not, the debate about whether genes affect intelligence is over.

## Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10 -8 ) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10 -6 ), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10 -6 ). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10 -29 ). These findings provide new insight into the genetic architecture of intelligence.

### Conflict of interest statement

The other authors declare no competing financial interests.

### Figures

Fig. 1. Regional association and linkage disequilibrium…

Fig. 1. Regional association and linkage disequilibrium plots for 18 genome-wide significant loci

Fig. 2. Results of SNP-based meta-analysis for…

Fig. 2. Results of SNP-based meta-analysis for intelligence based on 78,308 individuals

Fig. 3. Gene-based genome wide analysis for…

Fig. 3. Gene-based genome wide analysis for intelligence and genetic overlap with other traits