# Random Field Modelling of Genetic and Epigenetic Association for Congenital Heart Defects in the Presence of Disease Heterogeneity

> **NIH NIH K01** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $168,437

## Abstract

Project Summary/Abstract
This proposal for a Mentored Research Scientist Development Award is designed to provide the candidate the
necessary time and resources to transit into an independent statistical geneticist and genetic epidemiologist in
cardiovascular diseases, particularly in congenital heart defects (CHDs). This goal will be achieved through
enhanced training and research experience: 1) by taking didactic courses in areas related to birth defects
epidemiology, reproductive genetics and integrative genomics methodologies; 2) by implementing research
projects for genomic and epigenomic studies of CHDs; and 3) by assembling an expert panel of mentors with
extensive and complementary skills. The proposed K01 program will complement the candidate's previous
training in statistics, epidemiology and quantitative biology, optimize his effort to complete the proposed research
projects, and allow him to become an independent investigator. The (co-)mentors, Drs. Nianjun Liu and John S.
Witte, will advise the candidate's training in the domain of integrative genomics methodologies. The (co-)mentors,
Drs. Charlotte A. Hobbs, Benjamin Tycko and Jiali Han will advise the candidate's training in the domain of birth
genetics epidemiology and reproductive genetics. In the proposed projects, innovative biostatistical approaches
will be developed and applied to samples from the National Birth Defect Prevention Study (NBDPS), the largest
multi-site population-based study of birth defects ever conducted. We will utilize the genomic data (i.e. ~ 5 million
genetic variants) of ~ 1,000 case mother-father-infant triads and ~ 1,000 control mother-infant dyads, and the
epigenetic data (i.e. ~ 450K methylation sites) of 71 cardiac tissue samples. The proposed projects will address
three challenges in CHD research: 1) the genetic heterogeneity of CHDs, known as “all happy families are alike,
each unhappy family is unhappy in its own way”; 2) the functional effects of genetic variants within specific tissues,
such as the association between genetic variations and epigenetic modifications; and 3) the complex interactions
underlying CHDs, including the high-order interactions among genetic variants, epigenetic modifications and
maternal life style factors. The candidate has successfully completed a two-year KL2 Mentored Career
Development Award, entitled “detecting gene-by-gene and gene-by-environment interactions associated with
CHDs”, which provides a foundation onto which we will build more detailed studies to address the proposed
topics. The findings will likely provide insights into the underlying pathophysiological and etiological processes
that result in CHDs, and more importantly, can provide a direction for translational research leading to more
precise preconceptional counseling and interventions. The training and research experience gained from the
proposed study will serve as the groundwork for an independent research program, including a new R01 proposal
t...

## Key facts

- **NIH application ID:** 9849324
- **Project number:** 5K01HL140333-03
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Ming Li
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,437
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849324

## Citation

> US National Institutes of Health, RePORTER application 9849324, Random Field Modelling of Genetic and Epigenetic Association for Congenital Heart Defects in the Presence of Disease Heterogeneity (5K01HL140333-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849324. Licensed CC0.

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