# Discoveries in ADHD genomics: Help or hype in clinical settings?

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $741,614

## Abstract

In child psychiatry, the lack of biomarkers has been a hurdle to effective patient care. While efficient and
accurate characterization of help-seeking youth is a priority for the field, the current strategy of enumerating
signs and symptoms is limited by the subjectivity of assessment tools, the comorbidity and shared features
of different conditions, and the insidious pace at which severe, adult-onset neuropsychiatric illness unfolds.
Moreover, growing evidence suggests that traditional diagnostic boundaries do not reflect the biological
underpinnings of psychopathology. Thus, in the absence of objective indicators, it is difficult to resolve the
tension between proactive efforts to diagnose and treat youth who present for evaluation and concerns
around over-medication and over-labeling. In the past decade, genomewide association studies (GWAS)
have begun to reveal a polygenic component of risk for a range of psychopathology, reflecting the
aggregate influence of thousands of small-effect alleles. In other branches of medicine, such scores have
contributed to improved diagnostics and identification of at-risk individuals. Recently, members of our team
led the first significant GWAS for attention-deficit/ hyperactivity disorder (ADHD). In the current R01, we aim
to determine the potential for polygenic risk scores (PRS) from this study and from GWAS of severe adult
mental illness (SMI) to serve as objective risk indicators and tools for risk stratification in the child clinical
setting. To do so, we will augment our cohort of youth consecutively referred for neuropsychiatric evaluation
to achieve a sample of N=2500 child psychiatry outpatients. We will study this youth cohort in relation to
developmental period (childhood/ adolescence) and sex and also study ~15,000 adults from a biobank from
the same catchment area. Within a lifespan perspective, our aims will address gaps in the literature in order
to facilitate real world clinical translation of genomic risk scores. First, to determine the utility of ADHD PRS
as objective risk indicators, we will confirm their convergent and discriminant validity in relation to core
ADHD phenotypes across individuals with a range of psychopathology. Second, we will examine the utility
of ADHD PRS for risk stratification by relating scores to individual phenotypes with functional implications,
to multivariate symptom profiles across patients, and to patient groups derived from phenotype-based latent
class analysis. Third, we will determine the extent to which PRS for SMI and relevant biological pathways
associate with these criteria alone and in combination with ADHD PRS. Our pilot data in 1,294 youth and
5,140 adults support our aims and highlight the potential for PRS for different conditions to show
developmental differences that have implications for their use as risk indicators and risk stratification tools.
These findings and the expertise of our team (in psychiatric genetics, developmental psychopatholog...

## Key facts

- **NIH application ID:** 9986906
- **Project number:** 5R01MH116037-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** ALYSA E DOYLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $741,614
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986906

## Citation

> US National Institutes of Health, RePORTER application 9986906, Discoveries in ADHD genomics: Help or hype in clinical settings? (5R01MH116037-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9986906. Licensed CC0.

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