# Cognitive Genomics as a Window on Neurodevelopment and Psychopathology

> **NIH NIH R01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2021 · $544,297

## Abstract

PROJECT SUMMARY
Neurocognitive deficits represent a core component of several major neuropsychiatric disorders, including
schizophrenia, affective disorders, autism spectrum disorders, and attention-deficit/hyperactivity disorder
(ADHD), and the centrality of cognition to mental health is reflected in the RDoC matrix, in which “Cognitive
Systems” is one of the five fundamental domains of investigation. However, the genetic column of the RDoC
matrix is currently empty, as it has been recognized that the earlier generation of candidate gene approaches
lacked sufficient power and replicability.
The Cognitive Genomics Consortium (COGENT), led by the PI of this application, was formed earlier this
decade to perform large scale genome-wide association studies (GWAS) of cognitive phenotypes. Most
recently, we have meta-analyzed our results with other large-scale cohorts, resulting in two studies with
>100,000 subjects in each, which have finally identified dozens of genome-wide significant loci for general
cognitive ability (GCA). We have also demonstrated the significant genetic overlap, at the level of genome-
wide polygene scores, between general cognitive ability and most forms of psychiatric illness.
Deconstructing the genetic overlap between cognition and risk for neuropsychiatric illness can provide useful
etiological insights and help identify novel druggable targets. In the proposed study, we aim to extend our
cognitive GWAS to specific cognitive domains (e.g., verbal memory, working memory, attention, and
processing speed) with sample sizes in the tens of thousands for each. We will then utilize our general and
specific cognitive GWAS results to identify key molecular mechanisms and pathways that can identify
nootropic drug targets (Aim 1). We will then examine the molecular genetic overlap between our cognitive
GWAS results and psychiatric illness, utilizing novel analytic approaches to tease apart dissociable
mechanisms (Aim 2). Finally, we will utilize publicly available neuroimaging datasets with concomitant GWAS
data to examine the circuit-based, neurodevelopmental manifestations of cognition-relevant alleles and
polygene scores (Aim 3).

## Key facts

- **NIH application ID:** 10109016
- **Project number:** 5R01MH117646-04
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** TODD LENCZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $544,297
- **Award type:** 5
- **Project period:** 2018-06-08 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109016

## Citation

> US National Institutes of Health, RePORTER application 10109016, Cognitive Genomics as a Window on Neurodevelopment and Psychopathology (5R01MH117646-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10109016. Licensed CC0.

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