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.