Each group had its own polygenic profile, challenging the idea of a single underlying cause for autism.
Autism diagnosed during early childhood had a distinct genetic and developmental profile compared with autism diagnosed later, a large analysis of multiple cohorts showed.
The trajectory associated with earlier autism diagnosis had lower social and communication abilities in early childhood, reported Varun Warrier, PhD, of the University of Cambridge in England, and colleagues in Nature.
The trajectory linked with later autism diagnosis (typically, after ages 9-11) had more socioemotional and behavioral difficulties in adolescence.
Common genetic variants accounted for approximately 11% of the variance in age at autism diagnosis -- similar to individual demographic and clinical factors, which typically explain less than 15% of the variance, the researchers said.
The earlier diagnosis group had a low genetic correlation with attention deficit-hyperactivity disorder (ADHD) and mental health conditions. The later diagnosis group had stronger genetic correlation with ADHD and mental health conditions, including post-traumatic stress disorder (PTSD) and depression.
The results challenge a long-held assumption that autism has a unified underlying cause. In the unitary model, genetic variants are expected to be the same, regardless of age at diagnosis. This study, however, found that each group had its own polygenic profile and the genetic correlation between the two groups was small (r=0.38).
The term "autism" likely describes multiple conditions, Warrier noted. "For the first time, we have found that earlier- and later-diagnosed autism have different underlying biological and developmental profiles," he said in a statement.
Some genetic influences predispose people to show autism traits from a very young age and may be more easily identified, leading to an earlier diagnosis, Warrier pointed out.
"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," he explained.
"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," Warrier said.
The findings support the role of genes in autism, contrary to HHS Secretary Robert F. Kennedy Jr.'s claims that autism is a "preventable disease." A recent CDC study identified one in 31 children as having autism spectrum disorder, due in part to greater awareness, stronger surveillance, and broader diagnostic criteria.
Core features of autism spectrum disorder include persistent difficulties in social communication and interactions, along with restricted and repetitive behaviors, interests, or activities, noted Elliot Tucker-Drob, PhD, of University of Texas at Austin.
"Clinical diagnostic criteria generally require that these symptoms be observed in early childhood," Tucker-Drob wrote in a accompanying editorial. "However, the age at which a person is first diagnosed with autism varies considerably, ranging from the first years of life to adolescence and adulthood, even in individuals who were screened in early childhood."
This study presents evidence that the developmental timing of autism diagnosis is "not simply an artifact of the challenges of identifying milder cases at early ages, but rather a primary feature that distinguishes distinct forms of autism," Tucker-Drob wrote.
Developmental timing is "just one possible axis along which autism subtypes can be differentiated, and it is possible -- if not probable -- that other mechanistically separable subtypes of autism exist that have yet to be identified," he added.
In their analysis, Warrier and colleagues incorporated behavioral data from childhood and adolescence in the U.K. and Australia, and genetic data from over 45,000 people in cohorts from Europe and the U.S.
The study has important implications about how autism is conceptualized and provides a model to explain some of the diversity found in autism, the researchers noted.
"It makes me hopeful that even more subgroups will come to light, and each will find an appropriate diagnostic label," wrote Uta Frith, PhD, of the University College London, on the U.K. Science Media Center website.
"It is time to realize that 'autism' has become a ragbag of different conditions," Frith continued. "If there is talk about an 'autism epidemic,' a 'cause of autism,' or a 'treatment for autism,' the immediate question must be, which kind of autism?"