More challenging is to gauge the collective impact on autism risk of numerous variations in the genetic code shared by most people, which are individually much subtler in effect. Limitations of sample size and composition made it difficult to detect these effects and to estimate the relative influence of such common, rare inherited, and rare spontaneous variation.
Differences in methods and statistical models also resulted in sometimes wildly discrepant estimates of autism's heritability ranging from 17 to 50 percent.
Meanwhile, recent genome-wide studies of schizophrenia have achieved large enough sample sizes to reveal involvement of well over 100 common gene variants in that disorder. These promise improved understanding of the underlying biology and even development of risk-scores, which could help predict who might benefit from early interventions to nip psychotic episodes in the bud.
With their new study, autism genetics is beginning to catch up, say the researchers. It was made possible by Sweden's universal health registry, which allowed investigators to compare a very large sample of about 3,000 people with autism with matched controls. Researchers also brought to bear new statistical methods that allowed them to more reliably sort out the heritability of the disorder. In addition, they were able to compare their results with a parallel study in 1.6 million Swedish families, which took into account data from twins and cousins, and factors like age of the father at birth and parents' psychiatric history. A best-fit statistical model took form, based mostly on combined effects of multiple genes and non-shared environmental factors.
"This is a different kind of analysis than employed in previous studies," explained Thomas Lehner, Ph.D., chief of NIMH's Genomics Research Branch. "Data from genome-wide association studies was used to identify a genetic model instead of focusing just on
|Contact: Jules Asher|
NIH/National Institute of Mental Health