Rare gene variants linked to ADHD

Rare genetic factors that lead to attention deficit hyperactivity disorder appear to be some of the same ones that cause autism, schizophrenia and other brain disorders.

Previous studies have attempted – and mostly failed – to link common genetic variants to attention deficit hyperactivity disorder, better known as ADHD. A new study bolsters the idea that many different rare variants, some found only in single families or individuals, are responsible for the condition. What’s more, variants of the same genes associated with ADHD have also been linked to autism spectrum disorders, schizophrenia, bipolar disorder and intellectual disability.

“This really gives substance to the argument that there are shared genetic links between neuropsychiatric disorders,” says child psychiatrist Russell Schachar of the Hospital for Sick Children in Toronto, who led the study with Stephen Scherer, a geneticist at the hospital.

ADHD is one of the most common neuropsychiatric disorders, affecting about 7 percent of school-age children in the United States. It persists throughout life. People with the disorder may have trouble concentrating, act impulsively and be overly active. Symptoms fall on a continuum of severity, much like high blood pressure, says Josephine Elia, medical codirector of the Center for Management of ADHD at Children’s Hospital of Philadelphia.

Up to 75 percent of people with autism spectrum disorders also have symptoms of ADHD, but researchers did not know if the genetic causes were the same as in people who have ADHD alone. Previous research has shown that people with autism or schizophrenia often have genes that are missing or duplicated more often than normal. Such added or subtracted genes are known as copy number variants. Healthy people may have extra copies of several genes or lack some entirely, but missing or doubling up on certain genes can lead to disease (SN: 4/25/09, p. 16).

Unlike people with schizophrenia or autism, people with ADHD are no more likely than average to have missing or copied genes, the researchers report in the Aug. 10 Science Translational Medicine. But about 8 percent of people with ADHD have rare copy number variants that may cause or contribute to the disorder. A subset of those genes are perturbed both in people with ADHD and in people with autism spectrum disorders, indicating that the disorders may have some common genetic causes.

An examination of DNA from parents of 173 of the children in the new study showed that copy number variants associated with ADHD are often inherited from a parent who also often has the disorder. That differs from autism and schizophrenia, where the genes associated with the condition are often newly deleted or duplicated in the child with the disorder, not passed down from parents.

More copy number variants and other types of genetic changes remain to be uncovered, scientists say. Many different brain processes are probably involved in the disorders, and disrupting any of them could produce similar outcomes, Elia says. “We may end up having thousands of variants and not just a handful,” she says.