All ETDs from UAB

Advisory Committee Chair

Sara J Knight

Advisory Committee Members

Sara J Cooper

David S Batey

Thomas May

Cinnamon S Bloss

Document Type

Dissertation

Date of Award

2021

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

With recent advances in sequencing technologies, large scale genome wide sequencing has advanced our understanding of disease risk and etiology. These tests, however, often provide secondary data beyond the scope of the original sequencing objectives, and our understanding of how and if participants want to receive these secondary results is important as clinical and research-based sequencing becomes commonplace. To address this, we completed a systematic review of quantitative research that measures attitudes and preferences on the return of genomic sequencing results. Based on that review, we studied the return of genetic ancestry since these results, popularized in direct-to-consumer sequencing companies like 23andMe and Ancestry.com, have shown potential in advancing our understanding of disease. We completed semi-structured qualitative interviews with parents of children and newborns with conditions that were likely genetic in origin. These interviews focused on parental attitudes on, interest in, and preferences for receiving genetic ancestry results following clinical genome sequencing in a high stress environment, such as the neonatal intensive care unit (NICU). Finally, we looked at the bioinformatic infrastructure available for providing ancestry results to participants by comparing estimates generated from two publicly available sequencing databases, the Human Genome Diversity Project (HGDP) and the 1000 Genome project (1KG). We compared these estimates by datasets of known and unknown ancestry while also calculating congruence with self-reported race/ethnicity data from participants in the Alabama Genomic Health Initiative (AGHI). Taken together, we found that participants largely want results following genomic sequencing, preferring results that are actionable, preventable, and/or diagnostic. Participants are generally interested in secondary results, including genetic ancestry information, and find it potentially useful in its ability to inform clinical medicine. To return ancestry results to participants, researchers must consider the dataset they use to train their estimation software and the population on which estimates are being calculated. Our data show that the majority of participants want secondary results, including ancestry information, but that considerations for how ancestry results are calculated, interpreted, and returned, particularly in diverse and admixed communities, is of great importance as researchers explore the use of genetic ancestry in research and clinical medicine.

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