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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

AUTISM AND OBESITY: CO-OCCURRING CONDITIONS OR DRUG SIDE EFFECTS?

Principal Investigator

Principal Investigator

Talebizadeh, Zohreh

Description

Description

During the past several years, millions of dollars of research funding has been devoted to generating the rapidly growing amount of genetic information obtained from autistic subjects. Initiatives such as the autism Genetic Resource Exchange (AGRE) and Simons Simplex Collection (SSC) provide invaluable resources to the research community by collecting phenotypic data and ongoing generation of massive genetic data from subjects with autism. We designed a study to re-analyze already existing genetic data generated from autistic subjects from AGRE and SSC to address an important and previously unanswered question. Autism is a highly genetic condition, but researchers and doctors have been unable to determine the cause in most cases. The existing challenge in the reproducibility of genetic findings for autism is, in part, due to its extensive level of variation and severity of symptoms. Therefore, the most effective approach to address this obstacle is to find ways to classify subjects based on some shared features and then look for the genetic causes of autism separately for each subtype. This strategy has been successfully applied using some unique symptoms that may co-occur with autism (i.e., co-morbidity). For example, now it is well known and accepted that some individuals with autism may also have one of these features: severe language impairment, extremely large head size (macrocephaly), or gastrointestinal problems. Researchers have used these accompanying features as subject classification criteria to more successfully identify the genetic causes or mechanisms of autism. The objective of this pilot project is to better understand the relationship between autism and obesity. Despite recent suggestive links between autism and obesity, including (1) a higher prevalence of obesity in autism compared with controls, (2) maternal obesity and risk of autism in offspring, and (3) proven association of chromosome 16p11 with both autism and obesity, it is not clear if obesity is co-occurring with autism or is related to antipsychotic-induced weight gain (AIWG). Weight gain is one of the main side effects of the commonly used antipsychotics. Since the majority of patients with autism take antipsychotics, a general assumption is that the observed elevated rate of obesity in autism (i.e., 40%) is caused by AIWG. In addition to individual variations in weight gain, several lines of evidence from association, linkage, and twin studies have shown the role of genetics (i.e., single nucleotide polymorphism [SNP]) in AIWG. The existing gap in differentiating the two obese autistic subsets (i.e., with and without genetic predisposition for AIWG), has taken away a proper attention from uncovering the underlying mechanisms of potential co-occurrence of obesity with autism. Our hypothesis is that the prevalence of known AIWG associated SNPs in obese and non-obese autistic subjects is comparable; thus, AIWG cannot be the only reason for the observed higher rate of obesity. In our pilot study, we will demonstrate how re-analyzing already existing data (from AGRE and SSC families) by linking genotypes with phenotypes can provide an invaluable approach to increase our understanding of this complex condition. Our ultimate goal is to investigate a question: "Whether obesity should be considered as co-morbidity in autism or a reflection of antipsychotic drug-induced side effect?" Addressing this question directly requires recruiting subjects for a highly characterized longitudinal prospective study and utilizing expensive research resources. Since a huge research investment has already been devoted to establishing large autism repositories, we put efforts to design a research plan that can be performed using existing data. Therefore, we constructed an innovative approach to address this important question indirectly, in a retrospective study, by investigating an alternate question: "Whether obesity in autism is associated with known AIWG associated genetic factors?" This question can be easily addressed by re-analyzing existing genetic and phenotypic data. If the prevalence of AIWG-associated SNPs in obese and non-obese autistic subjects is comparable, it implies that AIWG cannot be the only reason for the observed higher rate of obesity. This innovative approach is constructed by linking biological concepts and relevant genetic susceptibility factors to clarify an unproven assumption (i.e., higher rate of obesity in autism is caused by AIWG), which is a clever way to test the hypothesis and steer science toward unraveling another critical co-morbidity in autism. This knowledge would raise awareness among (1) researchers to explore the mechanistic relation between autism and obesity leading to uncovering previously undetected etiological factors in autism and (2) caregivers to find more effective ways to treat obesity in autistic patients, since it would no longer be considered a drug side effect.

Funder

Funder

Department of Defense - Army

Fiscal Year Funding

Fiscal Year Funding

0

Current Award Period

Current Award Period

2014-2016

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 2SE. Launch three studies that target the underlying biological mechanisms of co-occurring conditions with autism, including seizures/epilepsy, sleep disorders, wandering/elopement behavior, and familial autoimmune disorders, by 2012. IACC Recommended Budget: $9,000,000 over 5 years.

Project Link

Project Link

AUTISM AND OBESITY: CO-OCCURRING CONDITIONS OR DRUG SIDE EFFECTS? (External web link)

Institution

Institution

Children's Mercy Hospital

State/Country

State/Country

Missouri

Project Number

Project Number

AR130398

Federal or Private?

Federal or Private?

Federal

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

AUTISM AND OBESITY: CO-OCCURRING CONDITIONS OR DRUG SIDE EFFECTS? | 0 | 2014 | AR130398
AUTISM AND OBESITY: CO-OCCURRING CONDITIONS OR DRUG SIDE EFFECTS? | 99820 | 2013 | AR130398

 
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