# Rare and common variants in complex disease

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $243,449

## Abstract

Analyses of common and rare genetic variation have produced key biological insights for many
complex diseases. However, for most diseases, including psychiatric disease, the bulk of
heritability remains unexplained. The genetics community is increasingly focusing on rare
variants, motivated by improvements in technology that are enabling the generation of large
whole-genome and whole exome sequencing (WGS and WES) data sets. A growing number of
high-profile studies on rare and common variant analysis have been published, including studies
published by the PIs of this renewal application and funded by R01MH101244. Nonetheless,
there are many unanswered questions about the genetic architecture of complex diseases.
Here, we propose a research program that will investigate complex disease architectures and
develop methods to optimally leverage rare and common variant contributions to produce new
biological discoveries.
We will assess contributions to disease heritability across the allele frequency spectrum; identify
gene sets and functional annotations that are enriched for disease heritability; and leverage
these findings to increase statistical power in studies of rare and common variants while
controlling for confounding. Our collaboration has multiple strengths: our statistical and
computational expertise; our extensive publication record in the previous funding cycle; our
track record of producing practical software that is widely used by the community; and our data-
driven approach, which ensures that the methods we develop will be broadly applied to
psychiatric and other disease data sets. We will guide our research using hundreds of
thousands of samples from large psychiatric GWAS, WES and WGS disease data sets.

## Key facts

- **NIH application ID:** 10204987
- **Project number:** 5R01MH101244-09
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** SHAMIL SUNYAEV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $243,449
- **Award type:** 5
- **Project period:** 2013-08-15 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10204987

## Citation

> US National Institutes of Health, RePORTER application 10204987, Rare and common variants in complex disease (5R01MH101244-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10204987. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*