Autism Is Not One Condition but Many, Suggests New Genetic Research

Why do some people receive an autism diagnosis in early childhood while others are identified much later?

Researchers at the University of Cambridge and international partners analyzed behavioral data from UK and Australian birth cohorts and found that the age of diagnosis reflects different developmental and genetic patterns, with later-diagnosed autism showing stronger links to mental health conditions.

“For the first time, we have found that earlier and later diagnosed autism have different underlying biological and developmental profiles,” said senior author Dr. Varun Warrier, an assistant professor at the University of Cambridge.

Autism diagnosis can happen early or late

Historically, autism has been seen as a condition that appears in early childhood, often diagnosed before the age of six years. However, large registry and cohort studies show new diagnoses continue into late childhood, adolescence and adulthood.

Children and adults diagnosed later tend to have higher rates of co-occurring conditions such as ADHD, depression and post-traumatic stress disorder. Past work has linked social, demographic and clinical factors to diagnostic timing; however, these factors only explain less than 15% of the variation.

Until now, the role gene variation can play in when autism is diagnosed had not been examined at scale.

The new study used longitudinal behavioral data from birth cohorts and genome-wide data from large autism cohorts to test two competing ideas: a “unitary” model, where autism has a single genetic basis, and a “developmental” model, where different sets of genetic factors shape how and when autistic traits emerge.

Autism study reveals genetic differences by age of diagnosis

Warrier and the team investigated four birth cohorts in the UK and Australia, where children were tracked across childhood and adolescence. Using these longitudinal datasets, along with the Strengths and Difficulties Questionnaire – a widely used tool for measuring social and behavioral development – they examined how social, emotional and behavioral traits changed over time. The team then analyzed genetic data from over 45,000 autistic individuals across the Danish iPSYCH study and the US-based SPARK study.

“We found that, on average, individuals diagnosed with autism earlier and later in life follow different developmental pathways, and surprisingly have different underlying genetic profiles,” said lead author Xinhe Zhang, a psychiatry PhD student at the University of Cambridge.

In one group, difficulties with social interaction, communication, hyperactivity and anxiety appeared early in life and remained relatively stable. These children were more likely to receive an autism diagnosis in early childhood.

In the second group, difficulties were less obvious in early years but increased sharply in adolescence. These children tended to be diagnosed later, often from late childhood onwards.

Common genetic variants explained ~11% of the variation in age at autism diagnosis. The researchers also identified two distinct polygenic factors – patterns of many small genetic effects – linked to earlier- and later-diagnosed autism.

The earlier-diagnosed factor was associated with social and communication difficulties in childhood and showed only weak connections to conditions such as ADHD or depression. The later-diagnosed factor was linked to difficulties emerging in adolescence and had strong overlap with ADHD, depression, PTSD and self-harm.

The overlap between the two profiles was modest. The later-diagnosed profile was genetically closer to ADHD and psychiatric disorders than to earlier-diagnosed autism.

“Some of the genetic influences predispose people to show autism traits from a very young age that may be more easily identified, leading to an earlier diagnosis. For others, genetic influences may alter which autism features emerge and when. Some of these children may have features that are not picked up by parents or caregivers until they cause significant distress in late childhood or adolescence,” said Warrier.

What autism diagnosis timing means for mental health support

The findings challenge the long-standing assumption that autism is a single condition with a shared cause. 

“The term ‘autism’ likely describes multiple conditions,” said Warrier.

Instead, the evidence points to autism as an umbrella term covering multiple biological and developmental pathways. The age at which someone is diagnosed may signal which pathway they are on.

This helps explain why autistic people diagnosed later often face more severe mental health difficulties. If their genetic profile overlaps more strongly with ADHD, depression and PTSD, then those risks are baked in from the start.

“Our findings suggest that the timing of autism diagnosis reflects more than just differences in access to healthcare or awareness, important as these are.

However, it is important to note that these are average differences on a gradient, so earlier and later diagnosed autism are not valid diagnostic terms,” said Zhang.

The study also highlights how support could be better timed. Interventions could be tailored not only to the individual’s traits, but also to when those traits are most likely to emerge.

The work also has implications for interpreting sex differences in autism. Since females are diagnosed later on average, some apparent sex effects may actually be effects of diagnosis timing.

However, genetics explained only ~11% of the variation in diagnosis age, leaving much down to social and cultural factors, such as healthcare access and stigma. The behavioral data came from one broad questionnaire, not autism-specific measures and the genetic analyses focused mainly on individuals of European ancestry.

“An important next step will be to understand the complex interaction between genetics and social factors that lead to poorer mental health outcomes among later-diagnosed autistic individuals,” said Warrier.

“Understanding how the features of autism emerge not just in early childhood but later in childhood and adolescence could help us recognize, diagnose and support autistic people of all ages,” Warrier added.

 

Reference: Zhang X, Grove J, Gu Y, et al. Polygenic and developmental profiles of autism differ by age at diagnosis. Nature. 2025. doi: 10.1038/s41586-025-09542-6

 

This article is a rework of a press release issued by the University of Cambridge. Material has been edited for length and content.