The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism
Abstract
:1. Introduction
2. Delineation of Locus and Gene Discovery in ASD
2.1. Chromosomal Rearrangements and Monogenic Syndromes Associated with ASD
2.2. Linkage and Candidate Gene Analysis
2.3. Microarray-Based Copy Number Variation Analysis
2.4. Whole Exome and Genome Sequencing
2.5. Genome-Wide Association Studies (GWAS)
3. Challenges and Future Directions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cohort/Consortium Studies | References and Website | History | Study Design | Current Size | Genomic Datasets |
---|---|---|---|---|---|
Autism Genetic Resource Exchange (AGRE) | [7,8] https://www.autismspeaks.org/about-agre (accessed on 20 May 2024) | Established in 1997 by Cure Autism Now (CAN), AGRE is currently funded by the National Institute of Mental Health and Autism Speaks, which merged with CAN in 2006. AGRE houses a collection of biomaterials and genetic and phenotypic data from families with ASD, made available to the greater scientific community | Simplex and multiplex families | ~2000 families | Genome-wide genotyping, WES, WGS |
Autism Genome Project (AGP) a | [9] https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000267.v5.p2 (accessed on 20 May 2024) | Established in 2004 by the National Alliance for Autism Research and the National Institutes of Health, AGP is now coordinated by Autism Speaks. The project involves more than 50 centers in North America and Europe that have pooled their DNA samples in a collaborative effort to examine families for SNPs and CNVs affecting risk for ASD | Simplex and multiplex families | ~2600 families | Genome-wide genotyping |
Simons Simplex Collection (SSC) | [10] https://www.sfari.org/resource/simons-simplex-collection/ (accessed on 20 May 2024) | Established in 2008 by the Simons Foundation Autism Research Initiative, SSC is a repository of clinical and genetic data from simplex ASD families designed to facilitate the discovery of rare and de novo variation | Simplex families | ~2600 families | Genome-wide genotyping, WES, WGS |
Psychiatric Genomics Consortium (PGC)–ASD Working Group | [11,12] http://www.med.unc.edu/pgc (accessed on 20 May 2024) | Founded in 2007 by Dr. Patrick Sullivan with the aim of conducting statistically rigorous and comprehensive GWAS meta-analysis for common psychiatric disorders. The ASD Working Group was founded at the start of PGC, in 2008, and currently includes 48 investigators from 10 countries | Simplex families, case-control | ~18,000 ASD cases b | Genome-wide genotyping |
Autism Sequencing Consortium (ASC) c | [13] https://genome.emory.edu/ASC/ (accessed on 20 May 2024) | Founded in 2010 by Dr. Joseph D. Buxbaum, the ASC is a large-scale international genomic consortium integrating several ASD cohorts and WES data from over 100 investigators. The project is funded by the National Institute of Mental Health with additional support from the National Human Genome Research Institute | Simplex families, case-control | ~12,000 ASD cases | WES |
Integrative Psychiatric Research (iPSYCH) | [14] https://ipsych.dk/en/about-ipsych (accessed on 20 May 2024) | Founded in 2012 by six leading Danish researchers in the fields of psychiatry and genetics, the project consists of a large Danish population-based case-cohort sample aimed at unraveling the genetic and environmental architecture of five of the most serious mental disorders (schizophrenia, ASD, ADHD, bipolar disorder, and depression) | Case-control | ~15,000 ASD cases d | Genome-wide genotyping, WES |
Hartwell Autism Research and Technology Initiative (iHART)/AGRE e | https://thehartwellfoundation.com/iHART.shtml (accessed on 20 May 2024) | Launched in 2014 by the Hartwell Foundation, the iHART database contains WGS data from multiplex families of the AGRE collection | Multiplex families | ~1000 families (~4500 ASD cases | WGS |
MSSNG a | [15] https://research.mss.ng/ (accessed on 20 May 2024) | Launched in 2014, the project is a collaboration between Autism Speaks, Verily, DNAstack, Hospital for Sick Children, and the research community. Its primary goal was to create the world’s largest WGS database of 10,000 individuals with ASD and their families with deep phenotyping | Simplex and multiplex families | 4258 families (5100 ASD cases) | WGS |
Simons Foundation Powering Autism Research for Knowledge (SPARK) | [16] https://www.sfari.org/resource/spark/ (accessed on 20 May 2024) | Established in 2015 by the Simons Foundation Autism Research Initiative, the project aims to establish a permanent repository of genetic samples from 50,000 families with ASD living in the U.S. | Simplex and multiplex families | ~50,000 ASD cases | Genome-wide genotyping, WES, WGS |
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Nóbrega, I.d.S.; Teles e Silva, A.L.; Yokota-Moreno, B.Y.; Sertié, A.L. The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism. Int. J. Mol. Sci. 2024, 25, 5816. https://doi.org/10.3390/ijms25115816
Nóbrega IdS, Teles e Silva AL, Yokota-Moreno BY, Sertié AL. The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism. International Journal of Molecular Sciences. 2024; 25(11):5816. https://doi.org/10.3390/ijms25115816
Chicago/Turabian StyleNóbrega, Isabella de Sousa, André Luíz Teles e Silva, Bruno Yukio Yokota-Moreno, and Andréa Laurato Sertié. 2024. "The Importance of Large-Scale Genomic Studies to Unravel Genetic Risk Factors for Autism" International Journal of Molecular Sciences 25, no. 11: 5816. https://doi.org/10.3390/ijms25115816