# Understanding the contribution of genotype-by-lifestyle interactions to cardiometabolic risk in individuals of east African ancestry

> **NIH NIH F32** · PRINCETON UNIVERSITY · 2022 · $67,174

## Abstract

ABSTRACT
Globally, dramatic changes in our environments are leading to increases in non-communicable diseases that are
determined by the complex interplay between our genetics and environment. Knowing why and how some
individuals are more sensitive than others to environmental perturbations remains a major gap in our
understanding of traits for which the genetic effects are environmentally dependent. To address this gap, we
have partnered with a subsistence-level community in northwest Kenya, the Turkana, who very recently initiated
a transition from a traditional lifestyle to an urban one and are in parallel showing increases in cardiometabolic
disorders. I propose to study molecular responses to this drastic lifestyle change in the context of inflammatory
mechanisms that confer increased risk for metabolic diseases. First, I will identify disruptions in coordinated
biological processes following the shift toward a Western lifestyle, through the detection of metabolic gene
network disturbances in PBMCs. Next I will identify genomic regulatory (ATAC-seq) and transcriptional (RNA-
seq) responses to in vitro pro-inflammatory stimulation in monocytes, wherein differential responses across the
lifestyle gradient in the Turkana will inform how chronic obesogenic signaling (in an urban environment) alters
acute inflammatory processes that typically occur in response to nutritional status. I will then identify the genetic
contribution to variation in monocyte pro-inflammatory responses and ask to what degree these genetic effects
are modulated by an individual’s lifestyle (i.e. genotype-by-environment interaction). Finally, I will ask to what
degree these loci explain inter-individual differences in health-related biomarkers. Because of the Turkana’s
unique history and current migration patterns, they are uniquely poised to study the health impact of rapid
environmental shift, as well as the degree to which genotype predisposes individuals toward vulnerability or
resilience in the face of environmental challenges (i.e. a western lifestyle). Addressing these important questions
in a largely understudied population of African ancestry has important implications toward global health and
precision medicine in African-Americans. Taken together, these Aims align with the NIH objectives, as they
involve understanding individual susceptibility to disease and risk across populations; and understanding the
pathobiology of the Western environment on our cardiometabolic health. My fellowship training plan will focus
on improving my quantitative skills, as I aim to build a research program focused on understanding the
contribution of genotype-by-environment interactions to cardiometabolic risk. This development will be enabled
by the mentorship from Dr. Julien Ayroles, who is an expert in systems and quantitative genetics and recently
initiated the Turkana Health and Genomics project at the core of this application. My interactions with the Ayroles
group and collabo...

## Key facts

- **NIH application ID:** 10537570
- **Project number:** 1F32ES034668-01
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Kristina Marie Garske
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537570

## Citation

> US National Institutes of Health, RePORTER application 10537570, Understanding the contribution of genotype-by-lifestyle interactions to cardiometabolic risk in individuals of east African ancestry (1F32ES034668-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10537570. Licensed CC0.

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