# Functional Characterization of the Genetic and Environmental Determinants of Complex Traits

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $298,239

## Abstract

Understanding the molecular and organismal function of genetic variants in non-coding regions is crucial to
dissect the genetic and evolutionary basis of variation in complex traits. Combining complementary functional
genomics datasets has proven a successful strategy to pinpoint the most likely causal variant and molecular
mechanism supporting a genetic association. Current existing annotations only capture regulatory conditions
at the baseline level. However, as we and others have shown, the effect of a genetic variant on a molecular
pathway, and ultimately on the individual's phenotype, may be modulated by the cellular environmental context
(gene-environment interactions, GxE). We define these genetic variants as GxE quantitative trait nucleotides
(GxE-QTNs) and consider the cellular environment as a simplified but better controlled proxy of the organismal
environment. Binding of TFs to specific genomic targets is defined by sequence motifs and chromatin epige-
netic marks, and can be altered by the presence of GxE-QTNs. To discover genes modulated by GxE-QTNs,
we have recently established a high-throughput approach to perturb the cellular environment by a panel of 50
in vitro treatments, including vitamins, metal ions, common drugs and hormones. Here we propose to use this
approach to dissect these GxE-QTNs and the underlying molecular mechanism by: i) performing functional ge-
nomics assays capturing chromatin accessibility; ii) analyzing the effects of naturally occurring genetic variation
in regulatory elements; and iii) combining RNA-seq, ATAC-seq, MPRA and GWAS data to co-localize association
signals and pinpoint complex traits causal variants.

## Key facts

- **NIH application ID:** 9928057
- **Project number:** 5R01GM109215-07
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Francesca Luca
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $298,239
- **Award type:** 5
- **Project period:** 2014-07-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928057

## Citation

> US National Institutes of Health, RePORTER application 9928057, Functional Characterization of the Genetic and Environmental Determinants of Complex Traits (5R01GM109215-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9928057. Licensed CC0.

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