Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Integration of polygenic risk and facial morphometrics to decipher the genetic susceptibility of orofacial clefting

Award Number: R01DE031261
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Integration of polygenic risk and facial morphometrics to decipher the genetic susceptibility of orofacial clefting - Abstract Orofacial clefts (OFCs) of the lip and/or palate are a prevalent congenital malformation with a complex genetic etiology driven by both common and rare genetic variants. OFCs are comprised of three major subtypes: cleft lip alone (CL), cleft lip with cleft palate (CLP) and cleft palate alone (CP) with genetic studies indicating both shared and unique factors contributing to each subtype. There has been remarkable success in discovering genetic loci associated with OFCs using genome wide association studies (GWAS); however, the relatively weak contribution of each individual locus toward overall disease liability has limited efforts to quantify an individual’s genetic risk for OFC. Over the past decade, novel methods have been developed to provide better measures of genetic liability for complex disorders by aggregating many subtle common genetic effects into a single, polygenic risk score (PRS). Application of a PRS to OFC cases would greatly aid in defining the heritable basis of many more cases, but two fundamental challenges have limited its current use: 1) the majority of OFC data has come from diverse populations, which confounds traditional PRS approaches; 2) assessments of PRS are typically performed on case/control study designs and aren’t optimized for the familial data found in most OFC studies. In this study we will perform innovative statistical techniques to overcome these previous limitations in PRS generation and explore OFC genetic susceptibility in a large OFC cohort (n = 24,195; 7,896 cases) comprised of 5 distinct ethnic groups (African, Admixed American, European, East Asian, Central /South Asian) (Aim 1). Moreover, to provide an even more robust measure of genetic liability for OFCs, we will examine the influence of 59 OFC-related 3D facial features in our OFC cohort with the goal of understanding how these traits may interact to increase OFC risk. Each of these analyses will both consider OFCs as a singular group as well as consider each of the individual subtypes independently. In Aim 2, we will apply sophisticated variant detection techniques to explore the contribution of rare structural and short variation on OFCs. This will allow us to leverage our large, aggregated OFC dataset to perform novel gene discovery by integrating rare and common genetic signals. Finally, we will stratify the PRSs generated in Aim 1 against the rare mutations discovered in Aim 2 to better understand how they may interact to confer OFC risk. This analysis will be further expanded by the development of an OFC composite genetic risk score, created by integrating the OFC PRSs directly with a rare variation risk score, to provide a more comprehensive measure of OFC genetic liability. Taken together, these aims are poised to greatly expand our understanding of the genetic risk factors for OFC across diverse populations and discover new genes associated with OFCs. Overall, this study will have a transformative impact on the OFC research community with potential applications in prenatal screening, genetic counseling, and treatments for the disorder.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $755,044 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	5	1/13/2026	NON-COMPETING CONTINUATION	$679,541
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	001	5	4/15/2026	NON-COMPETING CONTINUATION	$75,503
														Subtotal = $755,044

Issue Date FY: 2025 ( Subtotal = $762,829 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	001	4	5/5/2025	NON-COMPETING CONTINUATION	$76,282
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	4	12/12/2024	NON-COMPETING CONTINUATION	$686,547
														Subtotal = $762,829

Issue Date FY: 2024 ( Subtotal = $739,644 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	001	3	6/19/2024	NON-COMPETING CONTINUATION	$60,378
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	3	12/27/2023	NON-COMPETING CONTINUATION	$679,266
														Subtotal = $739,644

Issue Date FY: 2023 ( Subtotal = $771,384 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	001	2	2/22/2023	NON-COMPETING CONTINUATION	$77,137
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	2	1/25/2023	NON-COMPETING CONTINUATION	$694,247
														Subtotal = $771,384

Issue Date FY: 2022 ( Subtotal = $796,210 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	12/10/2021	NEW	$796,210
														Subtotal = $796,210

Grand Total All Awards = $3,825,111

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Integration of polygenic risk and facial morphometrics to decipher the genetic susceptibility of orofacial clefting

Award Number: R01DE031261

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer