Evidence map›Paper›PMID 42465919›Full record

ArticlemedRxiv : the preprint server for health sciences2026

A study of sex-specific genetic effects underlying risk of orofacial clefts also highlights the potential impact of sequencing errors due to short read mis-mapping.

Kanika Kanchan, Zeynep Erdogan-Yildirim, Seth Berke, Nandita Mukhopadhyay, Debashree Ray, Claire L Simpson, Jacqueline A Bidinger, Sarah W Curtis, Azeez Butali, Holger Schwender and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Kanika KanchanGenomics and Precision Health Section, Laboratory of Allergic Diseases, The National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
Zeynep Erdogan-YildirimCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Seth BerkeLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Nandita MukhopadhyayCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Debashree RayDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Claire L SimpsonDepartment of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.
Jacqueline A BidingerDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Sarah W CurtisDepartment of Human Genetics, Emory University, Atlanta, GA, USA.
Azeez ButaliDepartment of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Holger SchwenderMathematisches Institut, Heinrich-Heine-Universität, Düsseldorf, Germany.
Alan F ScottDepartment of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Joan E Bailey-WilsonNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Terri H BeatyDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Elizabeth Leslie-ClarksonDepartment of Human Genetics, Emory University, Atlanta, GA, USA.
Mary L MarazitaCenter for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Ingo RuczinskiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0003-3278-6274

Funding

Extending the Phenotype of Nonsyndromic Orofacial CleftsR01DE016148 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARAZITA, MARY L., WEINBERG, SETH M · 2004 to 2018
$19.7M
Whole Genome Sequencing for Orofacial Clefts, Incidental Findings and Role of Community GatekeepersR01DE028300 · NIDCR · UNIVERSITY OF IOWA · PI BUTALI, AZEEZ · 2020 to 2024
$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
Pittsburgh Craniofacial Sciences Training ProgramT90DE030853 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHARLES SFEIR · 2022 to 2026
$1.8M
International Consortium to Identify Genes and Interactions Controlling Oral ClefU01DE018993 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI BEATY, TERRI H · 2007 to 2008
$1.6M
MOLECULAR GENETIC EPIDEMIOLOGY OF CLEFT LIP AND PALATER01DE008559 · NIDCR · UNIVERSITY OF IOWA · PI MURRAY, JEFFREY C · 1988 to 2003
$1.5M
Differences between the sexes among genetic variants affecting orofacial cleft birth defect riskR01DE031855 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI MARAZITA, MARY L., RUCZINSKI, INGO · 2022 to 2025
$1.2M
NIDCR NIH HHS R01 DE008559NIDCR NIH HHS R01 DE016148NIDCR NIH HHS R01 DE028300NIDCR NIH HHS R01 DE031855NIDCR NIH HHS R01 DE032319NIDCR NIH HHS T90 DE030853NIDCR NIH HHS U01 DE018993
6 · The paper itself

Abstract

Orofacial clefts (OFCs), including cleft lip (CL), cleft palate (CP), and cleft lip with cleft palate (CLP), are among the most common craniofacial malformations in humans, with a birth prevalence of approximately 1 in 1,000 live births globally. Non-syndromic forms of OFC are predominantly genetic, with significant variability in prevalence across populations. Understanding the genetic underpinnings of OFCs remains a key public health priority, given the substantial medical and societal burden of these conditions. Recent genome-wide association studies (GWAS) have implicated numerous genetic loci, but challenges remain due to genetic heterogeneity and complex gene-environment interactions. This study aimed to identify sex-specific genetic risk factors for cleft lip with or without cleft palate (CL/P) through a meta-analysis of whole genome sequencing (WGS) data from 1,922 case-parent trios across eight diverse cohorts. Our approach revealed four SNPs in three distinct regions that showed genome-wide significant sex-specific effects. However, despite each of these SNPs passing standard quality control filters, follow-up analyses showed that these signals most likely were technical artifacts caused by sequencing errors, in particular mis-mapped reads due to sequence similarities with the sex chromo-somes. These findings highlight the necessity for careful scrutiny when studying differences between the sexes in genetic association studies.

Indexed as

Case-parent triosgenome-wide association studiesmeta-analysisorofacial cleftsread mappingrelative risk ratiosequencing errorssex-specific genetic effectssingle nucleotide polymorphismswhole genome sequencing

Identifiers

PMID42465919
PMCPMC13370597

What OpenQuestion holds

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Registered trials

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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.