# Integration of common, rare, and structural variation to define the genetic architecture of neuropsychiatric disorders

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $183,663

## Abstract

Abstract
Neuropsychiatric disorders (NPDs), including autism spectrum disorder (ASD), epilepsy, and schizophrenia, are
collectively common conditions in the human population. Many studies have shown that NPDs have a significant
genetic component, reaching upwards of 80-90% heritability, and include common and rare genetic variation
acting additively. However, much of this heritability remains unexplained by studies to date, which have largely
focused on inspecting isolated slices of the human genetic variation spectrum, focusing on gene discovery within
one specific NPD. This K01 proposes to provide extensive training and conduct in-depth analyses using an
integrative approach to statistical analyses that accounts for the complete spectrum of human genetic variation
across multiple NPDs. Such an approach will not only increase the power to uncover gene associations but will
also fill much-needed gaps in our understanding of the shared and distinct genetic architecture of NPDs.
In Aim 1 of this K01 proposal, I will receive extensive training in cross-NPD genetics, and will apply a rare variant
association framework to ASD, epilepsy, and schizophrenia for joint NPD gene discovery. For Aim 2, I will learn
new skills from leading experts in genetic association methods of common and noncoding variation for NPDs.
Finally, for Aim 3 of my proposal, I will combine my newly acquired expertise from Aim 1 and Aim 2 to develop
frameworks and methods that will account for variants ranging from common to rare, from single-nucleotide to
structural, and from coding to noncoding across NPD phenotypes to better define the complete genetic
architecture of these complex neurological phenotypes.
For this proposal, my mentors and I have developed a comprehensive training plan to continue my transition to
independence that will enable me to develop a research program at the forefront of neuropsychiatric genetics.
My academic background consists of my undergraduate training in statistics at Duke University and a PhD in
biostatistics from Johns Hopkins University. My postdoctoral training at the Center of Genomic Medicine (CGM)
and Department of Neurology at Massachusetts General Hospital (MGH) and at the Broad Institute has greatly
advanced my expertise in the genetics of complex disorders, especially ASD, and have cultivated my interest in
studying NPDs. The overarching goal of this career program is to expand my understanding of NPD biology
beyond ASD and to develop expertise in the modeling of common and noncoding variation. My mentors (Primary:
Dr. Talkowski, Secondary: Dr. Mark Daly) and advisory team (Drs. Kathryn Roeder, Alicia Martin, Elise Robinson,
and Jordan Smoller) will supervise my scientific progress and collaboratively provide mentorship for soft skills
development, including the responsible conduct of research, lab management, result communication, and grant
writing. This tremendous mentorship team and the cutting-edge training environment of this propo...

## Key facts

- **NIH application ID:** 10948257
- **Project number:** 1K01MH137407-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jack Minyang Fu
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $183,663
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10948257

## Citation

> US National Institutes of Health, RePORTER application 10948257, Integration of common, rare, and structural variation to define the genetic architecture of neuropsychiatric disorders (1K01MH137407-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10948257. Licensed CC0.

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