# Phenotypic profiling of ASD risk

> **NIH NIH R01** · BROAD INSTITUTE, INC. · 2020 · $505,426

## Abstract

PROJECT SUMMARY
Autism spectrum disorders (ASDs) are a group of neuropsychiatric conditions with a great deal of phenotypic
variability. Emerging genetic analyses have unequivocally demonstrated that a variety of genetic factors create
ASD risk, including common polygenic variation, de novo variation, rare inherited variation, and copy number
variation. To understand how these diverse genetic factors influence risk for ASDs, we will evaluate the full
spectrum of phenotypes with which they are associated, both in ASD cases and in the general population. In
so doing, we will identify types of ASD-associated genetic variation that appear similar in terms of phenotypic
impact and, critically, highlight types that diverge. To characterize the relationship between ASD genetic risk
and phenotypic heterogeneity in ASD cases, we will leverage a new resource of over 13,000 ASD cases from
the Danish national psychiatric registry. We will examine how common polygenic variation and rare protein
truncating variation (point mutations and CNVs) relate to phenotypic differences in ASD cases. These analyses
will identify subgroups of cases that share similar genetic etiology and phenotypic presentation, allowing us to
stratify ASD populations for research and eventual treatment development. Using data from two cohort studies,
we will also characterize the association between genetic risk for ASDs and behavioral and cognitive variation
in the general population. We will conduct a phenome-wide association study of the relationship between
common polygenic risk for ASDs and behavioral, cognitive, and medical variation in the Philadelphia
Neurodevelopmental Cohort (PNC; n=7500). In the Twins Early Development Study, we will examine the
general population relationship between rate of rare, protein truncating variation and each of: intelligence,
autism-like traits, psychosis-like traits, and traits of attention deficit disorder. Significant genetic associations
with general population phenotypes will facilitate interpretation of ASD risk variants, and inform our
understanding of clinical thresholds. The projects described in this proposal will significantly improve
understanding of ASDs heterogeneity and genetic influences.

## Key facts

- **NIH application ID:** 9935128
- **Project number:** 5R01MH111813-04
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Elise B Robinson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,426
- **Award type:** 5
- **Project period:** 2017-09-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935128

## Citation

> US National Institutes of Health, RePORTER application 9935128, Phenotypic profiling of ASD risk (5R01MH111813-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935128. Licensed CC0.

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