Evidence map›Paper›PMID 42723286›Full record

ArticleHGG advances2026

Trio-based GWAS reveals loci associated with different forms of isolated cleft lip.

Noah Herrick, Zeynep Erdogan-Yildirim, Myoung Keun Lee, Sarah W Curtis, Seth Berke, Grace C Brewer, Toby McHenry, Ahmed M El Sergani, Joel Anderton, Nandita Mukhopadhyay and 16 more

Abstract read
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In one paragraph

Article in HGG advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Noah HerrickCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: noah.herrick@pitt.edu.
Zeynep Erdogan-YildirimCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Myoung Keun LeeCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Sarah W CurtisDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Seth BerkeLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Grace C BrewerDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Toby McHenryCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Ahmed M El SerganiCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Joel AndertonCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Nandita MukhopadhyayCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Jenna C CarlsonDepartment of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
Terri BeatyDepartment of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
Azeez ButaliDepartment of Oral Pathology, Radiology, & Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.
Carmen J Buxo-MartinezDental and Craniofacial Genomics Core, School of Dental Medicine, University of Puerto Rico, San Juan, Puerto Rico, USA.
Jacqueline T HechtDepartment of Pediatrics and Pediatric Research Center, McGovern Medical School University of Texas Health, Houston, TX, USA.
Eric C LiaoDivision of Plastic, Reconstructive, and Oral Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Craniofacial Innovation, Children's Hospital of Philadelphia Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Lina M Moreno UribeDepartment of Orthodontics, College of Dentistry, University of Iowa, Iowa City, IA, USA.
Carmencita D PadillaDepartment of Pediatrics, College of Medicine, University of the Philippines, Manila, Philippines.
George WehbyDepartment of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, IA, USA.
Eleanor FeingoldDepartment of Statistics, College of Science, Oregon State University, Corvallis, OR, USA.
Jeffrey C MurrayDepartment of Pediatrics, School of Medicine, University of Iowa, Iowa City, IA, USA.
Ingo RuczinskiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Elizabeth J Leslie-ClarksonDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Seth M WeinbergDepartment of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
John R ShafferCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
Mary L MarazitaCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: marazita@pitt.edu.

Funding

Genetics Predoctoral Training ProgramT32GM149422 · NIGMS · EMORY UNIVERSITY · PI TAMARA J. CASPARY · 2023 to 2026
$2.2M
NIGMS NIH HHS T32 GM149422
6 · The paper itself

Abstract

Orofacial clefts (OFCs) are the most common craniofacial birth defect and comprise a diverse group of traits with complex and heterogeneous etiologies. Genetic studies of OFCs typically approach this diversity by stratifying cases into broad diagnostic classes, including cleft lip (CL), cleft palate (CP), and cleft lip with palate (CLP). Although this strategy has yielded important insights into OFC risk, it ignores the phenotypic heterogeneity within each subtype. CL exhibits marked phenotypic variability, involving differences in alveolar involvement, laterality, and sidedness that may reflect distinct etiologies. Given this phenotypic diversity within CL, we assembled a multi-ancestry cohort of 837 nonsyndromic CL case-parent trios with whole-genome sequencing and detailed phenotyping. We performed genome-wide association scans (GWASs) via transmission disequilibrium tests for CL overall and for 14 CL subtypes defined by involvement of the alveolus (with and without), laterality (uni- and bilateral), and sidedness (left and right). We identified four genome-wide significant loci. Two loci, IRF6 and 8q24.21, were both detected in the overall CL GWAS. PLCB1/PLCB4 and MAFB were detected in GWASs of alveolar cleft involvement and CL left-sidedness, respectively. These subtype-specific associations were followed by case-only comparisons that reflect the presence or absence of alveolus cleft or left-sided bias of CL to confirm the specificity of the association signal to the particular subtype. Our results provide evidence of within-class CL-subtype-specific genetic links for loci previously discussed in the context of primary OFC classes and demonstrate the value of granular OFC subtype characterization to capture trait-specific associations.

Indexed as

Cleft LipGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyCleft PalateHumansInterferon Regulatory FactorsMafB Transcription FactorPhenotypePolymorphism, Single NucleotideInterferon Regulatory FactorsIRF6 protein, humanMAFB protein, humanMafB Transcription Factoralveolus cleftcleft lipGabriella Miller Kids Firstgenetic modifierleft unilateral clefttrio-based GWAS

Identifiers

PMID42723286

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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.