# Methods for leveraging family-based designs and summary data to elucidate complex trait genetics

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $409,375

## Abstract

ABSTRACT
 To better understand genetic basis of complex human traits, two fundamentally different and complementary
designs employed in genome-wide association studies (GWAS) are population-based and family-based designs.
With the advent of biobanks and large-scale biomedical databases, recent years have seen an explosion in
genetic studies of adult traits/diseases, and consequently, a rapid advancement in methodology for population-
based designs that these biobanks depend on. In contrast, methods for family-based designs have received little
to no attention although they play an important role in the investigation of genetic basis of low-prevalence/rare
disorders and of child health outcomes. Analysis methods based on family-based designs can protect against
population stratification and admixture (thus allowing for racial/ethnic diversity among participants), and can be
more powerful than a population-based study of similar sample size. Another consequence of large-scale
biobanks is the public availability of aggregate-level genotype-trait association results (or GWAS summary
statistics) for a wide spectrum of complex human traits, including molecular traits that are intermediate between
genotype and a disease-related trait. Methods that can leverage GWAS summary statistics to understand biology
underlying diseases are in high demand since they are nearly as efficient and avoid logistical/ethical concerns
related to sharing individual-level data. In this application, I propose a research program of developing
novel statistical methods and open-access tools for genetic epidemiology studies, with a particular
focus on family-based designs. Some of these methods/tools will leverage only association summary
statistics to innovatively integrate omics with disease data, thereby helping improve understanding of
regulatory mechanisms underlying human health. We seek to address some of the open problems of human
trait genetics, including methodological challenges in identifying non-additive genetic effects (e.g. gene-gene
interaction, gene-environment interaction, parent-of-origin effect), effects of rare variants, and in prioritizing
causal variants through integrative omics. We will bring obscure mathematical functions from statistical literature
to real public health applications while illustrating them on existing databases. This research program will
support diversity in three distinct ways: methodological advancement of family-based designs that overcome
challenges related to racial/ethnic diversity in participants; efficient methods/tools that allow genomic researchers
to conduct genetic epidemiology studies using publicly available summary data even in resource-poor
environments; and help train diverse graduate students recruited annually by the Johns Hopkins School of Public
Health. In the last 5 years, I have built a research profile in family-based genetic studies alongside population-
based ones, have developed cutting-edge methods based on...

## Key facts

- **NIH application ID:** 10906837
- **Project number:** 5R35GM150836-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Debashree Ray
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906837

## Citation

> US National Institutes of Health, RePORTER application 10906837, Methods for leveraging family-based designs and summary data to elucidate complex trait genetics (5R35GM150836-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10906837. Licensed CC0.

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