# Research Project 2 - Genomic Approaches to Pollutome Effects on Risk of Major Depression in Hispanic Pedigrees

> **NIH NIH U54** · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2024 · $594,574

## Abstract

SUMMARY
Major depressive disorder (MDD) is characterized by an extended episode of a persistent feeling of sadness or
a lack of interest in outside stimuli. It is among the most common mental illnesses, affecting 16.2% of individuals
in the US during their lifetime. MDD is a heterogeneous disorder with a variable clinical course, an inconsistent
response to treatment, and little established etiology. Arguably, our lack of understanding of the causes of the
disorder hinders improvements in prevention, diagnosis, and treatment.
Multiple risk factors predispose MDD, including demographic characteristics (e.g., sex, age, and ethnicity),
behavior and lifestyle-related modifications (e.g., addiction, socioeconomic status, immigration status, stressful
life events), and both endogenous (e.g., infectious agents) and exogenous environmental factors (e.g., exposure
to pollutants/contaminants/toxins). In addition, MDD risk is substantially heritable. However, our ability to identify
novel environmental risk factors has been limited by a lack of sufficiently broad environmental measures.
Recently, evidence has been accumulating that exposure to pollutants influences the risk of MDD, although most
studies have employed indirect exposure estimates. Here we propose to measure person-specific levels of
organic and inorganic pollutants to search for environmental determinants of recurrent MDD (rMDD) risk in large
multigenerational pedigrees from the Mexican American Family Study (MAFS). A wealth of phenotypic and
genetic information exists on the members of the randomly ascertained families in this cohort. Specifically, we
previously documented high rates of depression in these families, estimated the heritability of rMDD (h2=0.46),
and localized genetic loci using linkage and whole genome sequencing (WGS) approaches. Recently, we
developed a novel family-based approach to control for genetic factors and thereby increase the power to detect
causal environmental signals influencing disease risk. This analytic approach makes it possible to optimally
detect novel environmentally driven determinants of rMDD risk. Given the pedigree-based design and preexisting
phenotypic and WGS data, the MAFS cohort provides a powerful efficient resource for studying environmental
components of rMDD risk and will provide important new insights into the etiology/mechanisms of MDD risk. Our
specific aims are: 1) to obtain individual-level direct measures of the pollutome including a set of 72 persistent
organic pollutants and 28 metals in banked plasma samples from two time points and indirect spatially-imputed
measures of air pollutant exposure; 2) to detect the influence of pollutants on rMDD risk using a novel statistical
approach to control for the effect of genetic factors to maximize environmental pollutant signals; 3) to detect
genotype×pollutome interactions in rMDD risk; and 4) to replicate results in an independent set of 750 Mexican
American individuals from the Rio Grande ...

## Key facts

- **NIH application ID:** 10930973
- **Project number:** 5U54HG013247-02
- **Recipient organization:** UNIVERSITY OF TEXAS RIO GRANDE VALLEY
- **Principal Investigator:** John Blangero
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $594,574
- **Award type:** 5
- **Project period:** 2023-09-18 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930973

## Citation

> US National Institutes of Health, RePORTER application 10930973, Research Project 2 - Genomic Approaches to Pollutome Effects on Risk of Major Depression in Hispanic Pedigrees (5U54HG013247-02). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10930973. Licensed CC0.

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