avi (abraham) reichenberg , phd
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National Health Registers and Autism Research. Avi (Abraham) Reichenberg , PhD. Outline. Genetic and environmental factors in autism liability. Finding and ruling-out environmental risk factors for autism: Cross and multigenerational investigations. Mega registry studies. - PowerPoint PPT PresentationTRANSCRIPT
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Avi (Abraham) Reichenberg, PhD
National Health Registers and Autism Research
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Outline
• Genetic and environmental factors in autism liability.
• Finding and ruling-out environmental risk factors for autism: – Cross and multigenerational investigations.– Mega registry studies.
• Building you own autism registry.
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A-B-C of twin studies
A-B-CA. MZ twins share 100% of
their genesB. DZ twins share 50% of their
genesC. MZ/DZ ratio of a trait
reflects etiological influences on that trait.
Example:• Correlation between a trait
(e.g., height) between two twins:
• MZcorr=0.5
• DZcorr=0.2• Heritability= 2X(MZcorr-DZcorr)=0.6
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Strong genetic contribution to autism liability
Lichtenstein et al. Am J Psychiatry. 2012
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A new view on autism and related conditions
Before After
Slide: Joseph Buxbaum
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Genomic architecture of ASDCommon genetic variations
(SNPs) acting together can increase risk for ASD
Related syndromes/ Chromosomal abnormalities
Rare genetic mutations (CNVs) alone may be considered causative
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Common variants and ASD
Devlin et al., 2012
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Related syndromes
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Copy-number variation and ASD
Devlin et al., 2012
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Don’t forget the environment!
Lichtenstein et al. Am J Psychiatry. 2012
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The new view on autism and related conditions should also consider the
environmental space
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The first (modern) register
• The population register in Sweden dates back to the 17th century.
• Requiring the names and dates of those born or passed away.
• Created to increase the efficiency of tax collection and military recruitment.
• According to the population census, the number of population in the country was 2,175,124, of whom 410,400 lived in the territory of Finland.
• The population size was considerably lower than expected, and the information on population number was declared secret.
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MMR vaccination and autism
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Intrauterine growth
Sandin et al. 2013
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SSRI and pregnancy outcome
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SSRI and Autism
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Folic Acid and Autism
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The challenges
Self report vs. Independent observations/measurement
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Advancing maternal age
Sandin et al. JAACAP 2012
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Advancing paternal age
Hultman et al. Molecular Psychiatry (2011) 16, 1203-1212;doi:10.1038/mp.2010.121
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International Collaboration for Autism Registry Epidemiology (ICARE)
• ICARE combines data from 6 population-based registries of AD/ASD with additional demographic and familial/perinatal data.– Sweden– Norway– Denmark– Finland– Israel– W Australia– US (California) – coming soon!
• ~ 31,000 cases of ASD.• ~ 20,000 cases of autism. • ~ 3,000,000 non-cases
Registry I
•Demographic
Registry II
•Mental health
Registry III
•Pregnancy information
Schendel et al. JADD 2013
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International Collaboration for Autism Registry Epidemiology
Schendel et al. JADD 2013
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International Collaboration for Autism Registry Epidemiology
Schendel et al. JADD 2013
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Federated database
Schendel et al. JADD 2013
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Cross generational effects
•Medications in pregnancy•Environmental toxins•Impaired growth•Preterm birth
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Benjamin Franklin and Multigeneration Effects
• Ran away from home• His son, William had problematic family
relationships with his children.• His grandson…….
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Why study multigenerational effects?
• Utilizing Quasi Experimental Designs Better understanding of confounding and causality.
D'Onofrio et al. Child Dev. 2010Lichtenstein et al. Am J Psychiatry. 2012
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Why study multigenerational effects?• Some risk factor disease associations
may not be limited to events in a single generation.
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The new new thing
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The new new thing
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Health Registry-based Triad+
• Reliable AND valid (but sometime just valid) case-identification registries allowing for continuous follow up.
• Linkable other population based registers– Service– Health– Demographics– Family relations– Biological materials
• Analytic infrastructure– Epidemiologists– Psychologists/socielogists– Statisticians
+ Openness to collaborations+ Access to data
Cases
Other registers Analytics
Unique identification number used by all data sources and allowing individual linkage
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AcknowledgmentsInternational Collaboration of Autism Multigenerational FamIlial and Environmental Registry Epidemiology (ICARE) Risk for Autism (MINERvA) Network
• Diana Schendel Christina Hultman• Sven Sandin Micki Bresnahan• Kim Carter Ezra Susser• Richard Francis Mika Gissler• Theres Grønborg Raz Gross• Mady Hornig Amanda Langridge • Anastesia Nyman Helen Leonard• Eric Parner Abdre Sourander• Camila Stoltenberg Paul Surén• Nina Gunnes Stephen Levine• Joseph Buxbaum Jonathan Mill• Alexander Kolevzon Jakob Christensen• David Hougaard Mads Hollegaard• Yudi Pawitan Paul Lichtenstein• Emma Frans Sebastian Lundstrom
• Autism Speaks partner for ICARE: Michael Rosanoff NIH partners for MINERvA: Alice Kau, Deborah Hirtz, Cindy Lawler