Evidence map›Paper›PMID 41674607›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Leveraging the genetics of human face shape boosts the discovery of orofacial cleft risk loci.

Noah Herrick, Seppe Goovaerts, Alexandra Manchel, Myoung Keun Lee, Xinyi Zhang, Amy Davies, Jenna C Carlson, Elizabeth J Leslie-Clarkson, Sarah J Lewis, Mary L Marazita and 4 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Noah HerrickCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0009-0004-3251-8311
Seppe GoovaertsDepartment of Human Genetics, KU Leuven, Leuven, BE.ORCID 0000-0001-5176-8552
Alexandra ManchelDepartment of Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-6946-3829
Myoung Keun LeeCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Xinyi ZhangDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
Amy DaviesBristol Dental School, University of Bristol, Bristol, UK.ORCID 0000-0001-7234-0539
Jenna C CarlsonDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-5483-0833
Elizabeth J Leslie-ClarksonDepartment of Human Genetics, Emory University, Atlanta, GA, USA.ORCID 0000-0002-5735-1712
Sarah J LewisPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0003-4311-6890
Mary L MarazitaCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Justin CotneyDepartment of Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-8230-2157
Peter ClaesDepartment of Human Genetics, KU Leuven, Leuven, BE.ORCID 0000-0001-9489-9819
John R ShafferCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0003-1897-1131
Seth M WeinbergDepartment of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-9467-4556

Funding

The Genetic Architecture of Human Facial MorphologyR01DE027023 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CLAES, PETER, SHAFFER, JOHN R · 2017 to 2024
$5.2M
Unraveling mechanisms of genome regulation to understand and improvehuman healthR35GM119465 · NIGMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI COTNEY, JUSTIN LEE · 2016 to 2025
$3.9M
Genomic Risk Variants in Orofacial Clefting: Discovery and Functional ValidationR01DE032319 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mary L. Marazita, Stephen A Murray · 2023 to 2026
$2.8M
Investigating the role of genes, maternal exposures, and interactions on orofacial cleftsR01DE032122 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHAFFER, JOHN R · 2022 to 2024
$2.1M
Functional characterization of craniofacial enhancers at single cell and single base pair resolutionR01DE028945 · NIDCR · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI COTNEY, JUSTIN LEE · 2019 to 2023
$1.9M
Pittsburgh Craniofacial Sciences Training ProgramT90DE030853 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHARLES SFEIR · 2022 to 2026
$1.8M
Integrated multi-omics analyses of early mammalian craniofacial developmentR03DE028588 · NIDCR · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI COTNEY, JUSTIN LEE · 2020 to 2021
$328k
NIDCR NIH HHS R01 DE027023NIDCR NIH HHS R01 DE028945NIDCR NIH HHS R01 DE032122NIDCR NIH HHS R01 DE032319NIDCR NIH HHS R03 DE028588NIDCR NIH HHS T90 DE030853NIGMS NIH HHS R35 GM119465Wellcome Trust
6 · The paper itself

Abstract

Several lines of evidence suggest that normal-range facial features and nonsyndromic orofacial clefts (OFCs) exhibit a shared genetic basis. Approaches designed to leverage this relationship hold the possibility of revealing new OFC risk loci by boosting discovery power. To test this idea, we applied a pleiotropy-informed GWAS method (cFDR-GWAS) with summary statistics from large, independent European GWASs of normal facial shape (n=4,680; n=3,566) and nonsyndromic cleft lip with or without cleft palate (nsCL/P, n=3,969). The cFDR approach identified 21 independent genomic loci significantly associated with nsCL/P, providing further evidence of the interconnected genetic architecture between these traits. The five original nsCL/P GWAS signals were detected and joined by nine additional loci previously implicated in other OFC association studies. The remaining seven loci represent new nsCL/P genomic regions, and three of these replicated (P < 0.05) in an independent nsCL/P cohort:

Indexed as

cFDR-GWASCleft CollectiveFacial morphologyOFCOrofacial cleft geneticspleiotropy-informed GWAS

Identifiers

PMID41674607
PMCPMC12889762

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.