The team developed new methods to discover gains and losses of DNA, or copy number variants (CNVs), from exome sequencing, and methods to integrate data from these CNVs with other classes of de novo and rare inherited variants, and identified 72 genes associated with autism. Feliciano.Ī second study also published in Nature Genetics, "Rare coding variation provides insight into the genetic architecture and phenotypic context of autism," led by a team of investigators supported by the Simons Foundation Autism Research Initiative (SFARI) and the Autism Sequencing Consortium (ASC), performed analyses on genetic data from 20,627 people with autism, with new genetic data derived primarily from SPARK. So far our data strongly support this hypothesis," said Dr. We hypothesized that people with autism who have these inherited genetic variants are not as likely to have seizures and cognitive differences as people with de novo genetic variants. "The majority of parents who passed down these genetic variants in our study do not have cognitive differences or autism, but we know that these genes are associated with autism because we find that these variants are more frequently inherited by children with autism. Individuals with autism who carry inherited variants in these "moderate effect" genes are less likely to have cognitive differences than people with autism who carry LOF variants in well-established autism genes, such as CHD8 and SCN2A. Of these genes, five have not previously been implicated in neurodevelopmental conditions. In this meta-analysis, they identified 60 autism genes whose contribution to autism is largely driven by rare inherited loss of function (LOF) variants transmitted by parents who do not have cognitive differences or autism. The researchers next added in another 22,764 individuals with autism and 236,000 people without autism from the general population. However, this means that although known autism-associated genes are responsible for the majority of de novo variants, there are others still to be identified. Nearly 70 percent of this genetic contribution can be attributed to known autism or neurodevelopmental disorder genes.
#Research participants full
To gain a better understanding of the full spectrum of autism genes, the researchers analyzed 19,843 participants with autism, along with one or both of their biological parents, and found that roughly 20 percent of people with autism have de novo genetic variants that affect the function of the associated gene. "We have now identified a group of genes associated with autism, that can include inherited variants, which begin to explain a different part of the autism spectrum." "For many years, we have known from twin studies that there must be inherited genetic variants that lead to autism, but we have not been able to systematically identify individual genes until now," said lead author Pamela Feliciano, Ph.D., SPARK's scientific director. However, only 20 percent of individuals with autism have this type of genetic variant. Most genetic variants of this type associated with autism have profound effects on the brain in those individuals when they occur. Most of these variants are also implicated in other neurodevelopmental disorders (NDDs). It is widely known that autism is heritable, but previous studies have primarily identified autism genes with de novo variants (DNV) - variants that occur spontaneously in germ cells prior to conception - that are not inherited. This largest-ever autism cohort allowed researchers to identify a group of novel "moderate-effect" genes that tend to contribute to autism through inherited variants. Researchers analyzed the DNA of almost 43,000 people with autism, including 35,000 participants from the SPARK autism research study, as part of SPARK's ongoing effort to understand the full spectrum of autism genetics. One study, "Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate effect genes ," was published in Nature Genetics on August 18, 2022. We are now appreciating that the genetic contributions to different phenotypes vary in terms of the genes involved when those genes are activated during brain development and how common some of the genetic variants are in the population," said Wendy Chung, M.D., Ph.D., principal investigator of SPARK. "Autism is a spectrum, and includes individuals with profound autism who often have cognitive differences and/or epilepsy, as well as individuals who are talented and exceptional, often in specific areas.