# Genetic neuroscience: How human genes and alleles shape neuronal phenotypes

> **NIH NIH U01** · BROAD INSTITUTE, INC. · 2020 · $4,125,261

## Abstract

Genetic studies have identified many specific loci with significant associations to psychiatric disorders.
However, unless we can develop useful approaches for systematically turning genetic information into
neurobiological insights about brain disorders, there is a danger that costly and hard-won genetic findings will
not be exploitable to understand pathophysiology and generate important therapeutic hypotheses.
The goal of our collaborative, interdisciplinary effort is to develop powerful, generalizable approaches for
discovering how risk variants for psychiatric disorders shape neurobiological processes at multiple levels of
analysis, and to identify the processes whose dysregulation underlies disease. To do this, we propose to
develop new experimental and inferential systems to bridge a longstanding gap between human genetics and
experimental biology. We aim to identify biological causes and effects that span the genetic, molecular,
and cellular levels of the nervous system.
Our interdisciplinary team will develop new experimental systems that measure genetic influences across
levels of analysis (RNA, proteins, and cellular function including physiology) in precise, scalable, well-
controlled ways. We will make use of emerging cellular systems including three-dimensional cortical spheroids
and organoids, and radically novel “population in a dish” experimental systems that collect data on cells from
hundreds of donors in a shared environment, inferring donor identity at the time of phenotypic readout. The
analysis of such systems in turn requires sophisticated inferential strategies and new ideas from computer
science. We propose to develop and widely share experimental and computational resources, including cell
lines, methods, datasets, and analytic tools.
The successful completion of this work will identify key neurobiological processes for multiple psychiatric
disorders, and fortify many other scientists in making such connections in their own work. We hope in so doing
to create a new kind of interdisciplinary science that – by combining the strengths of data-driven, unbiased
human genetics with the power of emerging experimental systems – transforms the rate at which human-
genetic leads lead to insights about disease mechanisms.

## Key facts

- **NIH application ID:** 9989904
- **Project number:** 5U01MH115727-04
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Paola Arlotta
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $4,125,261
- **Award type:** 5
- **Project period:** 2017-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989904

## Citation

> US National Institutes of Health, RePORTER application 9989904, Genetic neuroscience: How human genes and alleles shape neuronal phenotypes (5U01MH115727-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989904. Licensed CC0.

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