Investigators: Emma Glasson, Helen Leonard, Kim Carter, Kingsley Wong, Nan Hu, Richard Francis
This resource established by the MINERvA Network represents international collaboration and data sharing across seven geographic locations (Western Australia, Denmark, Sweden, Finland, Norway, Israel and California). It allows access to combined population data on over 2.5 million births and nearly 34,000 cases of autism from these seven sites, and uses innovative technology to allow data to be shared globally but remain protected. This allows an amazing opportunity to investigate risk factors for autism in a way that is not possible in smaller individual datasets.
Better understanding of the aetiologic roles of family history, prenatal environmental factors, and potential biologic mechanisms, such as epigenetic changes, in autism spectrum disorders (ASD) are research priorities identified in the Autism Coordinating Committee 2011 Strategic Plan for Autism Spectrum Disorder Research, but rapid progress has been hampered by the challenges of acquiring relevant data in large epidemiologic samples. The goals of Minerva are to examine: (1) fundamental controversies concerning familial and environmental contributions to risk for ASD; (2) transmission of risk across generations; (3) investigate pregnancy-related environmental factors in ASD, and (4) the potential role of epigenetic changes in those factors.
The MINERvA network provides for a multi-national population-based cohort study which includes more than 2.5 million births and 33,769 cases of autism spectrum disorder from Western Australia, Denmark, Sweden, Finland, Israel and California. This resource allows more accurate and precise determination of the contributions of familial and environmental factors to the etiology of autism, in particular whether medications for maternal chronic and acute conditions prescribed in pregnancy contribute to ASD risk, and whether epigenetic processes underlie a biological abnormality linked to autism. From a public health perspective, the study will accelerate the characterization of high risk groups, modifiable risk factors and the elucidation of mechanisms in autism etiology that could ultimately contribute to preventive measures or interventions and treatments. Based on population data from 5 countries, a recent publication showed the heritability of ASD was estimated to be approximately 80%, indicating that the variation in ASD occurrence in the population is mostly owing to inherited genetic influences, with no support for contribution from maternal effects. A further paper estimated autism recurrence. Compared with the risk in unaffected families, there was an 8.4-fold increase in the risk of ASD following an older sibling with ASD and a 17.4-fold increase in the risk of childhood autism following an older sibling with childhood autism. A 2-fold increase in the risk for cousin recurrence was observed for the 2 disorders. There also was a significant difference in sibling ASD recurrence risk by sex.
Our group with Kingsley Wong and Emma Glasson is leading the analysis investigating the role of maternal valproate, primarily used for the treatment of epilepsy but also for bipolar disorder, in the development of autism in the offspring.
External collaborators: Avi Reichenberg (Mount Sinai School of Medicine), Stephen Levine (University of Haifa), Sven Sandin (Mount Sinai School of Medicine), Mady Hornig (Columbia University), Diana Schendel (Aarhus University), Stefan Hansen (Aarhus University), Gayle Windham (California Department of Public Health), Michaeline Bresnahan (Columbia University), Dan Bai (The Chinese University of Hong Kong), Mika Gissler (National Institute for Health and Welfare), Benjamin Hon Kei Yip (The Chinese University of Hong Kong), Christina Hultman (Karolinska Institutek), Andre Sourander (University of Turku), Camilla Stoltenberg (The Norwegian Institute of Public Health), Erik T. Parner (Aarhus University), Auli Partanen Suominen (University of Turku), Christine Roth (Columbia University), Heli Malm (University of Helsinki), Jakob Christensen (Aarhus University Hospital), Ezra Susser (Columbia University)