# Comprehensive analysis of genetic pleiotropy in eleven neuropsychiatric disorders

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $431,469

## Abstract

ABSTRACT
The long-term goal of this proposal is to understand the shared genetic bases of psychiatric disorders to
improve prevention, diagnosis, and treatment of these serious illnesses. Recent successes of large-scale
genomics studies have verified extensive sharing of common variant risk across major psychiatric disorders at
a genome-wide level. Nevertheless, little is known of which and how certain genetic loci carry risk effects
transcending traditional diagnostic boundaries. To fill in this critical gap, we propose for the first time the
systematic identification and functional characterization of genetic effects shared among eleven
neuropsychiatric disorders using genome-wide SNP data on over 1 million individuals. Our central hypothesis
is that there are pathogenic mechanisms shared amongst broad domains of psychiatric disorders, one of which
centers on the development of the nervous system and chromatin remodeling that governs brain-specific gene
expression. In support of this hypothesis, preliminary data based on eight neuropsychiatric disorders show that
more than a hundred of genetic risk loci carrying significant and robust pleiotropic effects are enriched among
brain-active genes critical to cell identity, cell differentiation, and transcriptional regulation. In this study, we will
use genome-wide genetic data of unparalleled size and scope to achieve the following three aims with
independent benefits: (1) to uncover a comprehensive spectrum of pleiotropic risk effects spanning eleven
neuropsychiatric disorders; (2) to systematically evaluate the characteristics of pleiotropic risk genes; and (3) to
identify biological mechanisms commonly altered by pleiotropic risk genes underlying psychopathology.
Through this unique and powerful study, we expect to gain new insight into how pervasive genetic pleiotropy
shapes the etiology and structure of psychopathology. This study will also produce novel analytic methods and
strategies that are applicable in any cross-disorder genetics studies, providing immediate and significant
impact to the research community.

## Key facts

- **NIH application ID:** 9887499
- **Project number:** 1R01MH119243-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Phil H. Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $431,469
- **Award type:** 1
- **Project period:** 2019-12-18 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9887499

## Citation

> US National Institutes of Health, RePORTER application 9887499, Comprehensive analysis of genetic pleiotropy in eleven neuropsychiatric disorders (1R01MH119243-01A1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9887499. Licensed CC0.

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