From the 2005/2006 Distinguished Lecturer Series. Abstract: Epidemiology is the scientific study of the occurrence of disease in human populations. Basic principles of epidemiological research designs (cohort, case-control, prevalence, ecological studies) and analysis (risk and confounding factors) will first be introduced. Autism prevalence studies have shown upward trends in rates in the last 20 years. The best current prevalence estimate for all autism spectrum disorders combined is 0.6%. Possible interpretations for the higher prevalence figures will be discussed. In particular, two separate hypotheses have focused on child immunization schedules as potential explanations for the increased rates of autism. The MMR (measles-mumps-rubella) hypothesis has been evaluated in several studies that have failed to demonstrate an increased in the risk of autism following exposure to MMR. The thimerosal hypothesis has linked the total cumulative exposure to ethylmercury up to age 2 and an increased risk of autism. Yet, epidemiological studies have failed to demonstrate such an association. Current results will be discussed in the context of concerns by parents of autistic children on the causes and treatment of autism, and also of more general public health issues.

From the 2005/2006 Distinguished Lecturer Series. Abstract: Concerns have been raised about the role of immunization as a risk factor for autism. The measles-mumpsrubella vaccine (MMR) has been postulated to induce a new form of regressive autism with enterocolitis. Thimerosal, a mercury-based compound used to stabilize vaccines, has also been hypothesized to induce autism in infants and toddlers. Both hypotheses have been linked with increasing prevalence rates of autism spectrum disorders, suggesting that an epidemic of autism has occurred. Epidemiological data on rates of autism and other pervasive developmental disorders will be reviewed, with special reference to competing interpretations of time trends. The MMR and thimerosal hypotheses have been evaluated with cohort, case-control and ecological studies that will be summarized. The evidence accumulated in recent years currently favors the rejection of both hypotheses. Attention will also be paid to biological, public health and non-scientific issues which have influenced this debate.

From the 2005/2006 Distinguished Lecturer Series. Abstract: One of the major challenges to biomedical research in the 21st century is to devise strategies to identify the multigenic transmission patterns that correlate with common heritable disorders. Modern gene mapping studies are remarkably efficient for tracking the single-gene mutations responsible for most rare, Mendelian disorders, but inept for tracking the multigene inheritance patterns that predispose individuals to the type common heritable disorders that constitute the bulk of today’s public health burden. It appears that single gene surveys of disease-related genetic variation are limited to the detection of weak genotype:phenotype correlations when the phenotype is a disease classification and the underlying genotype is multifactorial. We are exploring experimental and computational genomic strategies to predict biologically meaningful interactions between key autism candidate genes with the hope that a systematic survey of allelic variation across predicted “candidate gene networks” will lead to improved genotype:phenotype correlation, and insight into the genetic basis of autism spectrum disorder.

From the 2005/2006 Distinguished Lecturer Series. Abstract: Family and twin studies indicate that for a majority of individuals diagnosed with autism and related spectrum disorders (ASD), a significant genetic predisposition to disease results from the cumulative effects of heritable genetic variants affecting multiple genes. Similar to most complex genetic disorders, identification of disease-predisposing genetic variation has been fraught with difficulty, and the main genetic clues to disease etiology result from the characterization of disease-causing mutations in a small minority of cases. Results from an ongoing collaborative gene mapping study of the Autism Genetic Resource Exchange (AGRE) study sample will be discussed in the context of other genetic studies, and with a view to the future prospects of identifying genetic determinants of common heritable disorders like autism.

From the 2005/2006 Distinguished Lecturer Series. Abstract: One of the major challenges to biomedical research in the 21st century is to devise strategies to identify the multigenic transmission patterns that correlate with common heritable disorders. Modern gene mapping studies are remarkably efficient for tracking the single-gene mutations responsible for most rare, Mendelian disorders, but inept for tracking the multigene inheritance patterns that predispose individuals to the type common heritable disorders that constitute the bulk of today's public health burden. It appears that single gene surveys of disease-related genetic variation are limited to the detection of weak genotype:phenotype correlations when the phenotype is a disease classification and the underlying genotype is multifactorial. We are exploring experimental and computational genomic strategies to predict biologically meaningful interactions between key autism candidate genes with the hope that a systematic survey of allelic variation across predicted "candidate gene networks" will lead to improved genotype:phenotype correlation, and insight into the genetic basis of autism spectrum disorder.