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Genetic, environmental influences equally important risk for autism spectrum disorder

In the largest family study on autism spectrum disorder (ASD) to date, researchers from the Icahn School of Medicine at Mount Sinai, along with a research team from the Karolinska Institutet in Stockholm Sweden and King's College in London found that individual risk of ASD and autistic disorder increased with greater genetic relatedness in families that is, persons with a sibling, half-sibling or cousin diagnosed with autism have an increased likelihood of developing ASD themselves. Furthermore, the research findings showed that "environmental" factors unique to the individual (birth complications, maternal infections, etc.) were more of a determinant for ASD than previously believed.

The population-based, longitudinal study, titled "The Familial Risk of Autism," was led by Abraham Reichenberg, PhD, Professor of Psychiatry and Preventive Medicine at the Icahn School of Medicine at Mount Sinai, and was first published online in the Journal of the American Medical Association.

"The findings from this extensive, prospective study will help improve how we counsel families with children who suffer from ASD and autistic disorder," said Dr. Reichenberg. "Currently, ASD affects nearly one percent of all children born in the United States. This study tells us that while we continue to study the genetic risk factors associated with ASD, we should find what environmental factors may play a role as well."

ASD is defined as impairment in social interaction and communication and the presence of restricted interests and repetitive behaviors; in the U.S., approximately one percent of the population is believed to have ASD. For purposes of this study, ASD included the definition for Asperger syndrome.

The study cohort comprised more than two million Swedish children born in 1982 through 2006, and included more than 1.6 million unique families. The breadth of this study allowed researchers the opportunity to examine a large spectrum of relatedness, including monozygotic (identical) and dizygotic (fraternal) twins; full siblings; maternal and paternal half siblings; and cousins. Single-child families were excluded from this study.

Researchers studied the relative recurrence risk, or RRR, for autism spectrum disorder and autistic disorder in these families and used it to determine heritability. Recurrence risk expresses the risk of having another affected family member in an already-affected family that is, the likelihood of a person in a family to be diagnosed with ASD if they have a sibling or cousin with autism spectrum disorder. RRR measures this recurrence in relation to disease in families without any affected members.

In calculating RRR for the different genetic relations, the researchers found that the closer the genetic relatedness, the greater the risk a sibling or cousin would also be diagnosed. Monozygotic twins had the highest adjusted RRR for ASD (estimated to be 153 times more likely to develop ASD); followed by full siblings (10.3 times), dizygotic twins (8.2), maternal half-siblings (3.3), paternal half-siblings (2.9) and cousins (2.0). Similar, if slightly higher, adjusted RRRs are found for autistic disorder: monozygotic twins (116.8), dizygotic twins (16.9), full siblings (14.6), maternal half-siblings (4.3), paternal half-siblings (2.9), and cousins (2.3).

Participants were followed for 20 years or until 2009, whichever came first. (Regular medical and developmental examinations are required for Swedish children as infants and throughout preschool.) At four years of age, a mandatory developmental assessment is conducted. From that assessment, children with suspected developmental disorders are referred for additional assessment. These assessments ensured completeness of data for the study.

This study held several advantages over previous studies, which may account for differences in research findings. The large sample size, established using data from multiple Swedish national registries, provided researchers with an unbiased population-based sample. Additionally, the length of follow-up time in this study increased the reliability of the finding results. This study was also one of the first to be able to accurately calculate RRR, by including twice as many cases of ASD and more detailed family data, including monozygotic and dizygotic twins and cousins, than previous studies.


Contact: Sid Dinsay
The Mount Sinai Hospital / Mount Sinai School of Medicine

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