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© Copyright 2018 Sarah C. Nelson © Copyright 2018 Sarah C. Nelson Third‐party interpretation of personal genetic data: the tools, users, and implications for policymaking Sarah C. Nelson A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2018 Reading Committee: Stephanie M. Fullerton, Chair Deborah J. Bowen Anna C. Mastroianni Program Authorized to Offer Degree: Public Health Genetics University of Washington Abstract Third‐party interpretation of personal genetic data: the tools, users, and implications for policymaking Sarah C. Nelson Chair of the Supervisory Committee: Stephanie M. Fullerton, DPhil Department of Bioethics and Humanities Individuals have unprecedented access to their “raw” or uninterpreted genetic data through direct‐to‐consumer (DTC) genetic testing, research participation, or clinical sequencing. Raw data can be transferred to a growing number of independent, third‐party interpretation (TPI) tools online for further analysis and interpretation across the domains of health/wellness, ancestry, and genealogy, yet little is known about who is using these tools, why, and with what outcomes. In this project I examined the tools, users, and implications for policymaking to better understand how the growing access to uninterpreted genetic data and various means to interpret it may unfold. First, I characterized TPI tools and interviewed tool developers, which revealed heterogeneity across tools in terms of the types of information returned and methods for returning it. Several developers portrayed tools as “bridging to the literature” rather than interpreting users’ data, in that tools linked user genotypes to information in publicly available databases of variant annotation and scientific literature. Second, I surveyed over 1,100 DTC genetics testing customers about their use of raw data and TPI tools. I found high rates of data download and use of multiple tools, including across the domains of health/wellness, ancestry, and genealogy. In follow‐up interviews, I found that social networking and general curiosity were common reasons for this cross‐domain use. Finally, to inform policymakers considering regulation in this space, I described DTC raw data provision and TPI as a distributed, supply chain system and identified scientific and technical aspects of each component in the system to inform policy discussions. I mapped some aspects of the regulatory landscape, focusing on U.S. federal health regulations, and concluded that existing regulatory mechanisms may not cleanly fit either DTC raw data or TPI tools and indeed may be constrained by First Amendment free speech protections. I conclude by summarizing my unique scientific contributions; offering recommendations for how to maximize benefits and minimize harms; and identifying avenues for further research, including to characterize an expanding set of DTC services and TPI tools, explore non‐DTC routes to raw data access and TPI tool usage, and examine potential policymaking in a global context. TABLE OF CONTENTS List of Figures ............................................................................................................................................... iv List of Tables ................................................................................................................................................. v List of Abbreviations .................................................................................................................................... vi Preface ......................................................................................................................................................... ix Introduction .................................................................................................................................................. 1 The upward trajectory of consumer genomics ......................................................................................... 1 Third‐party interpretation tools ................................................................................................................ 3 The Genomic Reformation ........................................................................................................................ 6 Additional routes to raw data ................................................................................................................... 8 Guiding research questions .................................................................................................................... 11 Science, Technology, and Society Studies perspective ........................................................................... 12 Chapter overviews: the tools, the users, and the policies ...................................................................... 15 Chapter 1: “Bridge to the literature”? Third‐party genetic interpretation tools and the views of tool developers ................................................................................................................................................... 17 Abstract ................................................................................................................................................... 17 Introduction ............................................................................................................................................ 18 Materials and Methods ........................................................................................................................... 19 Dataset ................................................................................................................................................ 19 Content Analysis ................................................................................................................................. 20 Interviews ............................................................................................................................................ 20 Results ..................................................................................................................................................... 21 Content analysis .................................................................................................................................. 21 User data: input formats, retention and sharing ............................................................................ 21 Type of results: genetic ancestry, genealogy and relatives, health and wellness .......................... 22 Analysis of user data: types and sources ........................................................................................ 24 Interviews with developers ................................................................................................................. 31 Explanations for bridging: scientific ................................................................................................ 33 Explanations for bridging: ethical ................................................................................................... 36 Explanations for bridging: regulatory ............................................................................................. 37 Discussion................................................................................................................................................ 38 Practice Implications ........................................................................................................................... 39 i Study Limitations ................................................................................................................................ 41 Research Recommendations .............................................................................................................. 41 Human Studies and Informed Consent ................................................................................................... 42 Chapter 2: “Well for five dollars, we'll see what it says”: a mixed‐methods study on consumer use of third‐party genetic interpretation tools ..................................................................................................... 43 Abstract ................................................................................................................................................... 43 Introduction ............................................................................................................................................ 44 Materials and Methods ........................................................................................................................... 45 Participant recruitment....................................................................................................................... 45 Survey design and implementation .................................................................................................... 46 Follow‐up interviews ........................................................................................................................... 46 Data analysis ....................................................................................................................................... 47 Results ..................................................................................................................................................... 50 Patterns of DTC testing ......................................................................................................................
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