The Autgo Initiative: Building a Bridge between Genetics and Outcomes Research

Background: While the field of autism genetics has rapidly expanded our understanding of the genetic factors contributing to autism, the ability to translate these discoveries into clinically meaningful information remains a significant barrier. Concerns over the need to improve translational aspects of autism research and engage community members have been noted in the literature and raised by patient advocates. In addition to the work done by patient advocacy groups, organizations such as the Patient-Centered Outcomes Research Institute (PCORI) support a change in the culture of research from being solely researcher-driven to becoming more patient-driven. One of the main reasons why this gap has been overlooked is the lack of communication between genetics and outcomes researchers.

Objectives: We used the PCORI engagement approach to address this barrier and develop a platform that would enable synergistic relationships between the two disciplines to facilitate utilization of genetic information in patient-centered studies.

Methods: Our project, Autism Genetics and Outcomes (AutGO), consists of two phases. In Phase I, we formed a community advisory board (n=33 members), and convened six sessions over a twelve month period. Sessions were structured as a combination of webinars, surveys, and in-person group discussions. Feedback was analyzed using content analysis strategies to identify themes. In Phase II, we formed an autism focus group (n=30 members), including outcomes and genetics researchers, clinicians, and parent representatives. An engagement/educational model was developed for the autism research community, including a research example that utilizes genetic information to address a patient-centered question.

Results: In phase I, we identified key barriers, facilitators, and needs, and distilled actions that may facilitate utilization of patient/parent perspectives in designing genetic research studies (Figure 1). In Phase II, we organized an educational workshop for the autism research community and developed an educational example to show the workflow, including study design and expected impacts for a patient-centered research approach. In this example, we showed how known genetic risk factors (SNPs) for a burdensome drug side-effect [antipsychotic-induced weight gain (AIWG)] could be evaluated to answer a health-related question in autism. We analyzed genotyping data for n=115 AIWG SNPs from >2000 probands from Simons Simplex Collection. BMI data was used to identify obese and non-obese subjects. Our results suggest that factors beyond drug side effects may contribute to the observed higher rate of obesity in autism. Furthermore, an association with rs7702361 (located in the RXFP3 gene) in autistic individuals with obesity was found, which appears to be independent of anti-psychotic medication use. The RXFP3 gene is implicated in eating disorders and our finding suggests that at least a subset of individuals with autism and obesity may have underlying metabolic problems. This information may help with treatment management for this population of patients.

Conclusions: The AutGO initiative has created a unique collaborative forum to facilitate the much needed dialogue between genetics and outcomes researchers, the applicability of which we are exploring on autism. This novel approach has the strong potential to contribute to improving the translational aspects of autism genetics research.