# Genetic Determinants of Outcomes in Diverticular Disease

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2022 · $166,861

## Abstract

PROJECT SUMMARY/ABSTRACT
Genetic data have the potential to improve the care of patients with the common colorectal disease
diverticulitis. Every year over 200,000 people are hospitalized with diverticulitis in the United States. Attacks of
diverticulitis are characterized by abdominal pain, fevers, chills, and gastrointestinal distress. For most
patients, attacks are mild and self-limited, but 10-35% go on to suffer severe disease: multiple hospitalizations,
colon perforation, and abdominal sepsis. Tens of thousands of patients undergo major surgery every year to
prevent severe disease. Currently, however, surgeons have no ability to predict which patients will have severe
disease. There is an unmet clinical need for improved understanding of the disease and risk stratification.
Historically, diverticulitis was considered an environmental disease related to diet, but data show clear
evidence of heritability; 40-53% of individual risk of diverticulitis is due to genetics. My preliminary work
described the genomic architecture of diverticulitis and identified 42 genetic loci associated with the disease.
This proposal builds on that preliminary work to further investigate the genetic contribution to diverticular
disease. My central hypothesis is that genetic risk factors can predict severity of diverticulitis, interact with
modifiable risk factors – such as visceral adiposity, and may manifest themselves as diverticulitis or as other
clinically-associated connective tissue traits including hernia, prolapse, and aneurysm.
The overall goal of this application is to support my training and development as an independent investigator in
genomic epidemiology. The career development plan includes completion of a master’s degree in
bioinformatics, structured mentorship, and enhancement of skills through performance of research. My main
research goal is to determine how a patient’s genetic background influences the development and course of
diverticular disease. The major themes of this project are reflect in the Specific Aims: 1) Generate and validate
a polygenic risk score for severe diverticulitis using four large biobanks, 2) Incorporate polygenic and
morphometric data to improve diverticulitis risk stratification by assessing the interaction of visceral adiposity
and genetic risk, 3) Investigate a common genetic causality for diverticular disease as a composite connective
tissue degenerative trait, examining an underlying genetic basis for phenotypes clinically linked to diverticulitis.
Successful completion of these studies will enhance our understanding of the role of genetics in diverticulitis,
lead to further large scale prospective research, and translate into meaningful genomic tools for patients with
diverticulitis.

## Key facts

- **NIH application ID:** 10559001
- **Project number:** 7K08DK124687-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lillias Holmes Maguire
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $166,861
- **Award type:** 7
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10559001

## Citation

> US National Institutes of Health, RePORTER application 10559001, Genetic Determinants of Outcomes in Diverticular Disease (7K08DK124687-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10559001. Licensed CC0.

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