Genetic Study Gives Clues to Intellectual Abilities

As students with bulging backpacks return to school this fall, each one also brings a unique skill set to the classroom. One child may be a math whiz, while their buddy in the next desk is an avid reader. A large genetic study conducted by experts at The Children’s Hospital of Philadelphia and University of Pennsylvania’s Perelman School of Medicine may lead to new ways to evaluate these complex traits in children’s intelligence.

The study drew on the largest data set ever used in a single sample across multiple cognitive traits grouped within five broad domains: executive function, memory, complex cognition, social cognition, and reading ability. Previous estimates of the heritability of cognitive traits relied on much smaller twin and family studies; however, the authors note that their current research represents a first step in discerning the overall genetic architecture of cognitive abilities.

The researchers performed genotypes of all participants, administered a battery of neurocognitive tests, and assessed participants in structured psychiatric interviews. They used a powerful gene software tool called genomewide complex trait analysis (GCTA) to analyze a subset of 3,689 individuals aged 8 to 21, all of European ancestry, drawn from the Philadelphia Neurodevelopmental Cohort, a general-population sample of close to 10,000 individuals who received care within CHOP’s pediatric network for a broad range of health needs.

The GCTA analyzes common SNPs (single-nucleotide polymorphisms, changes of a single base in DNA) to estimate how much these common gene variants contribute to differences in cognitive abilities within the total sample.

“When we computed the contribution of common variants to these cognitive abilities, we found that some of the contributions were substantial,” said one of the study’s two co-senior leaders, Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia.

For instance, common SNPs accounted for roughly 40 percent of the population differences in nonverbal reasoning, and 30 percent of the differences in language reasoning, with the balance of the differences attributable to rare variants and environmental factors. On the other hand, common gene variants together contributed to only 3 percent of the differences in spatial memory — the ability to navigate in a geographical location. The researchers also identified significant overlaps between trait domains. Reading ability, which was 43 percent attributable to common variants, was often inherited together with language reasoning abilities.

“Intuitively, it makes sense that skills in reading and language reasoning are related,” said Dr. Hakonarson, who added that those traits might be investigated together in future genetic and neurobiological studies.

Upcoming research also will focus on analyzing age-dependent differences to investigate how genetic influences vary as children mature. Other, larger studies should focus on non-European populations. Ultimately,  Dr. Hakonarson added, if the current findings are replicated and extended, researchers may be able to generate a genetic profile reflecting a normal distribution of cognitive abilities.

“Uncovering the genetic architecture of these diverse cognitive abilities may offer new insights into cognitive development and may ultimately allow investigators to identify useful biomarkers for diagnosing and predicting risks of neuropsychiatric conditions,” Dr. Hakonarson said.

The study appeared online July 15 in Molecular Psychiatry. Dr. Hakonarson’s co-senior author is psychiatrist Raquel Gur, MD, PhD, director of Neuropsychiatry in the Perelman School of Medicine at the University of Pennsylvania. The study team represents a collaboration among the CHOP and Penn investigators with colleagues at the Broad Institute, Harvard Medical School, and Massachusetts General Hospital who developed GCTA.

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