# Expanding the accessible genetic architecture of autism by single molecule sequencing

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $203,069

## Abstract

Previous studies have shown that maternal smoking during pregnancy increases risk for
neurobehavioral problems including autism spectrum disorder (ASD) and Attention Deficit
Hyperactivity Disorder (ADHD. It is thought that risk for neurobehavioral disorders in offspring is
attributable to in utero exposure of the fetus to nicotine. We propose an alternative genetic
mechanism to explain the increased risk of ASD to the offspring of chronic smokers. We
hypothesize that cumulative tobacco consumption by men and women prior to pregnancy could
result in increased rates of germline mutation in parental germ cells and lead to increased risk
for genetic diseases such as ASD in offspring. Preliminary results in our NIMH-funded study of
ASD show that maternal tobacco consumption is associated with higher rates of de novo
mutations in offspring. Our results suggest that some environmental risk factors for ASD could
be mediated in part by a genetic mechanism. To replicate and further characterize our findings,
we propose to (1) confirm the effect of smoking on germline mutation in an Illumina WGS
dataset of >350 families from cohorts that have been previously characterized by the Simons
Foundation and (2) to determine the differing effects of maternal and paternal smoking by direct
quantification of maternal and paternal mutation by nanopore sequencing. This study would be
the first to document and quantify an effect of parental tobacco consumption on the rates of
germline mutation. Such a finding would have significant implications for understanding the
interplay between genes and environment in determining risk for developmental disorders in
children.

## Key facts

- **NIH application ID:** 9986158
- **Project number:** 3R01MH113715-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jonathan Sebat
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,069
- **Award type:** 3
- **Project period:** 2019-10-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986158

## Citation

> US National Institutes of Health, RePORTER application 9986158, Expanding the accessible genetic architecture of autism by single molecule sequencing (3R01MH113715-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9986158. Licensed CC0.

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