# Decoding the Genetics of Sexual Dimorphism in Autism Spectrum Disorders

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $396,250

## Abstract

Our long-term goal is to use genetic tools to improve understanding, prevention, and treatment of autism
spectrum disorder (ASD). The objective of this proposal is to utilize knowledge about sexual dimorphism in
complex traits to extend our understanding of the genetic basis of a major risk factor for ASD, male sex. The
current hypothesis is that genetic sources of sexual dimorphism can occur at three levels: genomewide burden
or liability threshold, specific genetic loci representing gene-sex interaction, and relevant pathways or sets of
loci reflecting environmental sex contribution. In support of this hypothesis, previous work has shown that
genomewide genetic burden can differ by sex in cases ascertained for disease status and even in controls, risk
loci can be sex-specific, and polymorphisms differing in contribution to secondary sex characteristics by sex
impact disease risk. Our preliminary data also shows that genetic architecture differs between common
polymorphism and rare variant risk. In order to understand the action of sex-heterogeneous SNPs, we will
expand and refine their definition, establish their pathways of action, and test their mechanism of sex-
specificity. In order to establish a population baseline for sexual dimorphism of SNVs, we will assess both
genome-wide mutational burden and specific loci for sex differences and apply any new knowledge to ASD
data. Finally, we will utilize our knowledge about gene-sex interaction to identify functional noncoding genetic
variation relevant for disease risk. We expect to establish expectations about sex differences in genetic
architecture and show its utility to understanding disease biology. We will gain novel insight into complex
genetic mechanisms contributing to idiopathic ASD with implications for treatment and pioneer a generally
applicable approach for utilizing sex as a precision tool for complex genetic disease.

## Key facts

- **NIH application ID:** 9975223
- **Project number:** 5R01MH114924-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Lauren Anne Weiss
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2017-09-13 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975223

## Citation

> US National Institutes of Health, RePORTER application 9975223, Decoding the Genetics of Sexual Dimorphism in Autism Spectrum Disorders (5R01MH114924-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9975223. Licensed CC0.

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