# Investigating the role of genes, maternal exposures, and interactions on orofacial clefts

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $694,566

## Abstract

Project Summary/Abstract
Non-syndromic orofacial clefts are one of the most common birth defects worldwide. Genetic variation is
thought to play a major role in risk of non-syndromic clefts; indeed, several genetic risk loci have been
identified, to date. However, these loci cumulatively explain only part of the heritability, and for most of these
loci, the specific causal variants have not yet been determined. Moreover, recent work has suggested that cleft
subtypes (i.e., cleft lip alone, cleft lip with cleft palate, cleft palate alone, and subtypes defined by laterality and
completeness) may have partially overlapping and partially distinct etiologies, although the shared and
unshared genetic architectures of cleft subtypes are not well understood. Furthermore, maternal environmental
exposures (i.e., smoking, alcohol consumption, and folate) during pregnancy are known to influence cleft risk
and may interact with genetic factors as part of the underlying cleft liability. This proposal will seek to fill the
gap in knowledge regarding the genetic variants and their interactions with maternal exposures leading to overt
forms of clefts. This project will include analyses of existing data on our previously collected cohort comprising
cases with orofacial clefts, their immediate family members, and controls with no history of clefts. We will use
these data to perform genome-wide association studies and targeted gene-by-environmental interaction
analyses for orofacial clefts and subtypes. Understanding the genetic architecture of orofacial clefts may
ultimately lead to improved prediction of risk and recurrence, and may inform new preventive or therapeutic
interventions.

## Key facts

- **NIH application ID:** 10813780
- **Project number:** 5R01DE032122-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** John R Shaffer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $694,566
- **Award type:** 5
- **Project period:** 2022-07-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813780

## Citation

> US National Institutes of Health, RePORTER application 10813780, Investigating the role of genes, maternal exposures, and interactions on orofacial clefts (5R01DE032122-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10813780. Licensed CC0.

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