The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism

Abstract

Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System.

Figure 1

Environmental exposures and sources of information in the CHARGE study. The left-hand box indicates five classes of exposures that are candidates as environmental factors contributing to autism. The right-hand box lists sources of data available on CHARGE study participants. Arrows show a few examples of how specific exposures can be assessed. For example, pesticide exposures and/or their metabolites can be assessed in several ways (black arrows): laboratory assays can be conducted on blood (serum) and urine specimens; the interview collects information on applications in the home and also obtains residential histories that can be linked to exposure databases on commercial pesticide applications in California. Metals (blue arrows) can be measured in hair and in newborn blood spots obtained from the State Genetics Diseases Branch biospecimen bank or assessed by interview questions on fish consumption or use of household products. Exposures to infectious agents (dashed arrows) can be determined from medical records, self-reports, and assays on serum samples to test for seropositivity for antibodies to specific viruses.