Links between genetics and cognition change across childhood
Rare DNA changes are most strongly linked to cognition in early childhood, but the link fades as children age, while common DNA changes show stronger links later in childhood, new research finds.
Reported today (10 July) in Nature Human Behaviour, researchers at the Wellcome Sanger Institute analysed data from UK birth cohorts to investigate how genetic makeup can affect cognitive ability across early life.
The study may help explain why rare DNA changes associated with intellectual disability appear to cause the condition only in a subset of people who carry them. The findings also highlight the value of including genetic data in studies looking at how social and environmental factors influence cognition.
A person’s genetic makeup influences many traits, from our eye and hair colour to our height and personality. A major puzzle in clinical genetics is that some parents can carry rare genetic variants — differences in DNA — that can cause intellectual disability in their child, yet the parents appear unaffected themselves. This is known as ‘incomplete penetrance’ and is seen in many children with neurodevelopmental conditions.
In a new study, researchers at the Sanger Institute sought to understand how differences in genetic makeup between children relate to their cognitive ability as they age and how this compares with other early-life factors. ‘Cognitive ability’ refers to someone’s ability to solve problems, spot patterns, and remember things. It also influences educational outcomes and is linked to economic and health outcomes later in life.
Understanding the link between genetic makeup and cognition may therefore help explain not only why some children struggle at school, but why some genetic differences increase the risk for serious neurodevelopmental conditions.
The team analysed anonymised exome sequencing data — genetic information from the protein-coding portion of the genome — from 6,495 children from the Children of the 90s study, also known as the Avon Longitudinal Study of Parents and Children (ALSPAC),1 who had Intelligence Quotient (IQ) scores measured at ages four, eight and 16. They also used data from the Millennium Cohort Study (MSC)2 and UK Biobank to replicate some of their main findings.
The researchers looked into two broad types of genetic differences between people: rare and common variants. Rare variants are changes in DNA that are only seen in a small minority of people within a population and can disrupt or damage how a gene works. Common variants are millions of small differences spread across the genome that are seen in many people within a population, which don’t usually directly damage genes but often influence how active genes are.
The team found that the relationship between cognition and the two types of genetic variants move in opposite directions as children age. They found that the link between rare variants and cognitive ability was strongest in early childhood, at age four, but decreased with age, weakening by age 16. However, in a reverse effect, the link between common variants and cognitive ability strengthens as children age.
The researchers also compared genetic effects with other known influences on childhood cognition. The effect of a child’s common genetic variants on their IQ is at least as strong as the association with parental education. The effects of rare damaging variants on IQ were also comparable in size to those of being born prematurely or maternal illness during pregnancy, and these effects became weaker as children got older.
These findings suggest that rare genetic variants that affect cognition have their greatest influence during early childhood. This may help explain why some people who carry a rare damaging variant in a gene linked to intellectual disability do not appear to manifest the condition later in life – they may grow out of its early effects. This highlights early childhood as a critical window for understanding how genetic differences influences development. The researchers hope that future research confirms the relevance of these findings in neurodevelopmental conditions.
This study was made possible by recently generated exome sequencing data from three long-running UK birth cohorts,3,4,5 providing an unprecedented opportunity to explore how genetic variants influence development across childhood. Additional exome sequencing data from these cohorts will be released in the coming months, further expanding this resource for population health research.
“Our findings suggest that the effects of genetic variation can change substantially across childhood. We hope the findings encourage future research linking the genetics of cognitive ability in population-based cohorts to studies of intellectual disability.”
Dr Daniel Malawsky, first author at the Wellcome Sanger Institute
“This study demonstrates the value of generating and utilising exome sequencing data in large, well characterised, longitudinal population studies. As additional exome data become available, researchers will have even greater opportunities to investigate how genetic variation influences health and development throughout life.”
Professor Nic Timpson, Principal Investigator of Children of the 90s and Co-Director at Population Research UK
“This study illustrates the power of combining the UK’s world-leading expertise in genomics with the UK’s long-term investments in large population research cohorts, to understand the interplay between the different biological, social and environmental factors that influence cognitive development throughout life.”
Dr Matthew Hurles, Director at the Wellcome Sanger Institute
“Understanding when genetic differences matter most could transform how we study human development and help explain why the same genetic variant can have very different consequences from one person to another. In the future, these findings may inform genetic counselling for families of children with intellectual disability.”
Dr Hilary Martin, senior author at the Wellcome Sanger Institute
More information
Notes to Editors
- For more information on the Children of the 90s study, also known as the Avon Longitudinal Study of Parents and Children (ALSPAC), please see: https://www.bristol.ac.uk/alspac/. IQ scores were taken from ALSPAC.
- For more information on the Millennium Cohort Study, please see: https://cls.ucl.ac.uk/cls-studies/millennium-cohort-study/
- The three birth cohorts are:
- Avon Longitudinal Study of Parents and Children (ALSPAC)
- Born in Bradford (BiB)
- Millennium Cohort Study (MCS)
- For more information on exome sequencing data, please visit our blog: https://sangerinstitute.blog/2025/03/06/sequencing-decades-long-population-data-unlocks-health-insights/
- The exome data are freely available in the public European Genome-phenome Archive (EGA) database: https://ega-archive.org/
Publication
D. Malawsky, et al. (2026) ‘Common and rare genetic variant associations with cognitive performance across development in British cohorts.’ Nature Human Behaviour. DOI: 10.1038/s41562-026-02491-8
Funding
This research was supported by Wellcome. A full list of acknowledgements can be found in the publication.
