Researchers at Harvard Medical School have discovered a new genetic link between a subtype of autism spectrum disorder and abnormal regulation of blood cholesterol levels.
Published in Nature Medicine last month, the research found that genetic mutations underlying dyslipidemia — a condition characterized by abnormal levels of lipids such as cholesterol — were present in 6.5 percent of children on the autism spectrum.
While certain hallmark subtypes of autism, such as those associated with epilepsy and Fragile X syndrome, have a genetic basis that is well understood, scientists “still don’t understand the cause of most cases in most children with autism,” according to Pediatrics Lecturer Alal Eran, a first author on the study.
“We know their autism has a very strong inherited component, but we don’t understand what genes and what changes in these genes cause autism in most of these patients,” Eran said.
To help address that unknown, researchers sought to pinpoint genes which may be linked to ASD in patients, first poring over genetic data from children with autism and their relatives.
Nathan P. Palmer, a data scientist in the Medical School’s Department of Biomedical Informatics, said the researchers kept certain criteria in mind when looking for potentially relevant genes. Namely, they focused on genes which play a role in early brain development and may show different patterns of expression in males and females, since almost 80 percent of children on the autism spectrum are male, per Eran.
Ultimately, the researchers found that ASD patients and close relatives are more likely to carry mutations within certain genes which are known to regulate blood lipid metabolism. In order to confirm this pattern, they followed up by analyzing medical data from Boston’s Children Hospital and healthcare claims from a large U.S. insurer.
“Children with autism tend to have abnormal lipid levels in their blood that we can detect using routine blood tests, and looking at their medical records, they have a lot more mention of an explicit dyslipidemia diagnosis, meaning that there is some alteration in their blood lipid levels,” Eran said. “We also found that parents of children with autism tend to have more dyslipidemia diagnoses than parents of kids with other neurodevelopmental disorders.”
Eran said the discovery of a link between altered lipid regulation and a subtype of ASD may allow doctors to repurpose drugs approved for other purposes of modulating lipid levels to modify behavior and development in ASD patients. Still, she underscored that the research is still preliminary and will require further testing in animal models to confirm the link between autism and dyslipidemia before proceeding with human studies or developing targeted therapies.
“I don’t want my statement to suggest that we think that patients should now take cholesterol modulating drugs, or anything like that,” Eran said.
Medical School Biomedical Informatics Chair Isaac S. Kohane, another first author on the study, wrote in an email that he felt especially gratified during the research process by messages of support he received from patients and their families who “recognized—before many clinicians did—that their children differed in systematic ways from other children.”
“They’ve had to find their own paths to therapies customized to the various comorbidities that characterize the different diseases that are lumped together under that single label of autism,” Kohane wrote.
—Staff writer Ethan Lee can be reached at [email protected].
—Staff writer Meera S. Nair can be reached at [email protected].
