Genes In The Context of The Medical Phenome: The Challenges, Opportunities, and Pitfalls of Psychiatric Genetics Using Biobanks and Registries

Abstract

Overall Abstract The theme of the 2017 WCPG Meeting, “Genes in Context,” highlights the essential insights that become apparent when individual risk genes are considered in the context of polygenic background, epigenetic modifications in the cell, and environmental conditions and development. Similarly, the large-scale collection of genetic material integrated with the increasing availability of expansive phenotype information (“phenome”) from electronic medical records (EMR) allows a broader context in which to study the genetics of neuropsychiatric phenotypes. Identifying correlated phenotypes and assessing the broader role of implicated variants/genes are only a few of the many ways in which these studies could provide a unique lens through which to interpret genetic findings. The potential for these datasets to scale (e.g. 500k individuals for UK biobank) and the comprehensiveness of the captured phenome offers opportunities that are difficult to achieve in disease focused cohort studies. Initial work on these extraordinary datasets is already yielding exciting new findings with promising translational implications. Rigorous analysis of biobank data requires integrating multiple disciplines including genomics, epidemiology, informatics, ethics and the clinical domain of interest. We have assembled a diverse roster of researchers who bring expertise in these areas as speakers in this session. Co-chair Dr. Douglas Ruderfer, will introduce the session by presenting the opportunities, challenges and some initial successes of utilizing these resources. Next, Dr. Lea Davis will describe development of EMR-based algorithms for detection of neurodevelopmental disorders, results of an EMR-enabled biomarker discovery approach using Vanderbilt’s 270,000 patient biobank (BioVU), and community-engaged efforts to develop a more complete understanding of genomic privacy concerns related to participation in biobanks. Dr. Gerome Breen will then discuss general applicability of using the 500k-individual UK Biobank, along with details of a study in anorexia nervosa. Dr. Beate St. Pourcain will describe new results from her work examining genetic factors that contribute to the developmental trajectory of behavioral traits using the Avon Longitudinal Study of Parents and Children (ALSPAC) data set, and highlight implications when assessing trait-disorder overlap. Finally, Dr. Zhengming Chen will describe results of ongoing PheWAS of functional variants to assess causal associations (e.g. alcohol) in the 500K-person Kadoorie Biobank. Following the speakers, Dr. Jordan Smoller will lead a discussion focused on efforts currently underway to combine biobank resources through the psychEMERGE consortium and future resources available from the NIH All of Us project. Topics for discussion include genome-informed machine learning approaches to prediction models, structural equation models using genetic relationship data in cohorts, challenges to algorithmic portability, and opportunities for immediate translation of genomic findings. Symposium attendees will become familiar with (a) potential resources that are available to them, (b) strategies for maximizing the utility of such resources, (c) challenges in utilizing these resources, and (d) ethical issues related to genomic privacy in the context of biobanks. Finally, attendees will learn about novel discoveries emerging from biobank and registry resources in the United States, United Kingdom, and China.