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Title page for ETD etd-03242017-124753

Type of Document Dissertation
Author Simonti, Corinne Nicole
URN etd-03242017-124753
Title Leveraging Biobanks and PheWAS to Uncover the Health Consequences of Recent Human Evolution
Degree PhD
Department Human Genetics
Advisory Committee
Advisor Name Title
Doug Mortlock Committee Chair
David Samuels Committee Member
John A. Capra Committee Member
Josh Denny Committee Member
Will Bush Committee Member
  • PheWAS
  • Biobank
  • Neanderthal
  • Evolution
Date of Defense 2017-02-27
Availability unrestricted
The genomics era has seen a staggering increase in the number of whole genome sequences. This has bolstered studies of human populations, and revealed regions of the genome bearing signatures of selection and other demographic events. However, tying these regions to phenotypic effects in humans is difficult. I addressed this challenge by leveraging densely phenotyped biobank populations from the eMERGE network, a collection of 10 clinical biobanks across the US that connect electronic health records (EHRs) to genotyping data. The eMERGE data enabled me to interrogate the function of human genetic variation on a broad array of phenotypes using the phenome-wide association study (PheWAS) framework. Each chapter describes a project in which I tested hypotheses about the impact of evolutionarily important variants on human health. In the first, I examine the clinical impact of interbreeding between humans and Neanderthals; in the next, I evaluate variants whose allele frequencies have increased drastically since human divergence from chimpanzee; and finally I consider variants affected by GC-biased gene conversion, a recombination-associated mutational process that favors the fixation of G and C alleles. In conclusion, I used large clinical biobanks to uncover novel genotype-phenotype associations that reveal the effects of recent demographic events and evolutionary processes that have shaped the human genome.
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