# Air-pollution risk for Autism and ADHD - cross-disorder insights and genetic liability

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN MILWAUKEE · 2020 · $28,452

## Abstract

ABSTRACT
Neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity
Disorder (ADHD) are a major source of disability and loss of potential, as well as emotional and financial
hardship. Primary prevention of these disorders is of great public health importance, calling for the
identification of modifiable risk factors, such as environmental chemical exposures. ASD and ADHD are both
heritable but there is growing evidence that environment plays a role, and that environmental impact may be
influenced by genetics. Traffic-related air pollutants, including fine particulate matter (PM2.5) and nitrogen
dioxide (NO2) have biological evidence of neurotoxicity and human evidence that they may be risk factors for
ASD and ADHD. Only two prior studies have considered the influence of genetics on air pollutant risk in
neurodevelopmental disorders – each addressing a single gene – despite the fact that gene*environment
investigation can improve ability to detect the impact of environmental chemicals and add pathophysiological
insights. Prior studies are also limited in failing to consider co-diagnosis of ASD and ADHD, which is common,
and other sub-phenotypes that may better reflect etiologically homogenous groups impacted by air pollutant
exposure. The objective of this application is to conduct the largest single study of air pollutants with ASD
and ADHD to date, in the context of genetic variation. The central hypotheses are that higher exposure
during critical developmental windows to PM2.5 and NO2 will be associated with ASD and ADHD, the
associations will be influenced by genetic factors, and will vary according to neurodevelopmental sub-
phenotype. Our aims are: SA1: Deepen the mechanistic understanding of air pollutant risk on ASD, SA2:
Clarify a potential role of air pollutant risk in ADHD, and SA3: Investigate the specificity of
neurodevelopmental phenotypic subgroup associations with air pollutants, leading to cross-disorder
insights. For each aim, we will (A) estimate air pollutant main effects, (B) account for child and family genetic
modification of air pollution effects using a multi-faceted targeted approach among hundreds of loci, including
genes related to exposure biology and neurodevelopment, and (C) estimate these associations in an
exploratory genome-wide agnostic analysis using all available genetic markers. We will use a large,
population-based study in Denmark with existing genome-wide genotyping data – iPSYCH, including 16,146
children with ASD, 18,726 with ADHD (3033 with both), and 28,768 controls. We will add innovative well-
validated weekly estimates of PM2.5 and NO2 air pollution exposures during critical developmental periods at
both residential and employment locations. This work introduces key innovations including incorporation of
novel genetic markers in exposure risk assessment and considering neurodevelopmental sub-phenotypes. It
is significant in addressing modifiable causes of...

## Key facts

- **NIH application ID:** 10090141
- **Project number:** 3R01ES026993-04S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN MILWAUKEE
- **Principal Investigator:** Amy E Kalkbrenner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,452
- **Award type:** 3
- **Project period:** 2020-08-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090141

## Citation

> US National Institutes of Health, RePORTER application 10090141, Air-pollution risk for Autism and ADHD - cross-disorder insights and genetic liability (3R01ES026993-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10090141. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
