Novel Statistical Approaches For Imaging Genetics

Abstract

Modern medical bioinformatics encompasses a vast number of possible markers potentially useful for diagnosis. These markers may include structured clinical interviews, self-report questionnaires, inflammatory markers, multi-modal brain imaging (both structural and functional), and whole-genome genotyping. The number of possible individual inputs is thus in the hundreds or many thousands, and the factorial combination of such markers is even more vast. Moreover, some markers are easy and cheap to collect, whereas others are time consuming and/or expensive. In many applications, there is little guidance for clinicians on what information they should collect, when they should collect it, whether or not the added expense and effort is worth the extra information, and how to integrate all of these sources of information to provide a diagnosis, recommendation for treatment, or a prediction of outcome (prognostic judgment).We propose to address this situation by developing a theoretically sound algorithm that is robust to measurement differences, provides accurate predictions, and is intuitive to implement for clinician practitioners. Specifically, we will adapt methods of modern test theory (item response theory) to biomedical settings. The main idea is that we can consider different classes of markers as “testlets” to determine an underlying latent state (e.g., diagnostic status, responsiveness to a given treatment). As an extension to existing psychometric theory, we explicitly model dependency structure of the markers after conditioning on latent states (i.e., when local independence does not hold).This talk will also cover how these methods will be applied to the Adolescent Brain and Cognitive Development (ABCD) study, a nationwide 19 site NIH funded study that will recruit over 10,000 children aged 10-11 and followed for 10 years, with genetics, a twin component, and brain imaging every other year. The ABCD repository, which will be released to the public beginning December 1, 2017 and which will be of great value for imaging genetics studies, will be described in detail. The speaker, Dr. Thompson, is the Director of Biostatistics for the ABCD Consortium.