Simons VIP: Variation in Individuals Project
|Simons VIP Connect|
Visit Simons VIP Connect to join an online support community that links families with genetic changes to each other and to research opportunities.
The genetics of autism is complex and involves mutations in hundreds of genes, each of which accounts for a small percentage of autism. This heterogeneity in etiology makes it challenging to perform cohort studies in autism because associations may or may not be observed depending on the sample size and composition of any one particular patient cohort.
To probe the relationship between genotype and phenotype more deeply, SFARI launched the Simons Variation in Individuals Project (Simons VIP). The project aims to identify and study large numbers of individuals sharing recurrent genetic variants known to increase the risk of developing autism spectrum and other neurodevelopmental disorders. Longer-term goals are to use these data to develop targeted interventions and focused clinical care.
The Simons VIP first studied individuals with a deletion or duplication of chromosomal segment 16p11.2, the study’s immediate goal being to identify medical, cognitive, neural and behavioral profiles shared by those in this group.
Phase 1 of this project, which ended in early 2014, involved travel by individuals and families to clinical study sites. There, participants underwent extensive psychological and neurological testing, along with neuroimaging — including magnetic resonance imaging (MRI), functional MRI, and magnetoencephalography (MEG) — with a uniform protocol and DNA extraction from blood samples. Fibroblasts were cultured and cryopreserved for distribution to researchers interested in making induced pluripotent stem cells (iPSCs) or for other experiments. As a pilot project, Phase 1 also included testing a small number of 1q21.1 deletion and duplication carriers using the identical protocol.
|Phase 1: Copy number variants|
|Phase 2: Genes associated with features of autism|
Phase 2 – now underway – involves the collection of family, medical, developmental and behavioral information through online surveys and phone interviews by and with families. Phase 2 will permit expansion of the study by obviating the need for family travel and by enabling collection of longitudinal data. Importantly, this new phase will permit the rapid integration and study of new groups with recurrent genetic changes other than 16p11.2 and 1q21.1 deletions and duplications. To date, 46 single genes associated with developmental delay and features of autism have been incorporated into Phase 2 of the study (see Table 1).
Detailed medical history, phenotyping data and biospecimens for families (137 carriers of the 16p11.2 deletion and 127 carriers of the duplication; 23 carriers of the 1q21.1 deletion and 27 carriers of the duplication) are now available to researchers through SFARI Base, and new data are added quarterly. Whole-exome sequencing data are available for 507 Phase 1 participants. Structural and functional brain MRI images are available for many participants in the first phase of the study.
A paper published in Neuron further details the motivation behind the project and its design. To download "Simons Variation in Individuals Project (Simons VIP): a genetics-first approach to studying autism spectrum and related neurodevelopmental disorders," click here.
Research publications resulting from the Simons VIP can be found here.
Simons VIP data:
All Simons VIP data are available to approved researchers via SFARI Base.
Genetic data that are currently available are listed below. This list will be updated as more data becomes available:
Single nucleotide polymorphism (SNP) genotype data
- Duyzend M.H. et al. Am. J. Hum. Genet. 98, 45-57 (2016) PubMed, Data available through SFARI Base and NDAR
Whole-exome sequencing data
- Daly M.J. et al. (in preparation) Data available through SFARI Base
- Simons VIP Investigators
- Publications resulting from the Simons VIP
- List of neuropsychological tests and other phenotypic instruments used in the Simons VIP
- Induced pluripotent stem cell lines from Simons VIP participants