ArticlePloS one2017
A new approach to chromosome-wide analysis of X-linked markers identifies new associations in Asian and European case-parent triads of orofacial clefts.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Epidemiological insights into neural tube and orofacial malformations in Chile using data from the National Registry of Congenital Anomalies (RENACH).BMC pediatrics · 2025Article
- Hemizygous contiguous gene deletion within Xq28 that includes BCAP31, ABCD1, SRPK3 and SSR4: case report and literature review.Global medical genetics · 2025Article
- A ubiquitin-based effector-to-inhibitor switch coordinates early brain, craniofacial, and skin development.Nature communications · 2023Article
- The X-factor in ART: does the use of assisted reproductive technologies influence DNA methylation on the X chromosome?Human genomics · 2023Article
- Genome-wide Gene-by-Sex Interaction Studies Identify Novel Nonsyndromic Orofacial Clefts Risk Locus.Journal of dental research · 2022Article
- Aberrant cell segregation in the craniofacial primordium and the emergence of facial dysmorphology in craniofrontonasal syndrome.PLoS genetics · 2020Article
- Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors.Frontiers in cell and developmental biology · 2020Review
- Haplin power analysis: a software module for power and sample size calculations in genetic association analyses of family triads and unrelated controls.BMC bioinformatics · 2019Article
- Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Review
- Genome-wide interaction studies identify sex-specific risk alleles for nonsyndromic orofacial clefts.Genetic epidemiology · 2018Article
- The eXceptional nature of the X chromosome.Human molecular genetics · 2018Review
- Analysis of Parent-of-Origin Effects on the X Chromosome in Asian and European Orofacial Cleft Triads Identifies Associations withFrontiers in genetics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGWAS discoveries on the X-chromosome are underrepresented in the literature primarily because the analytical tools that have been applied were originally designed for autosomal markers. Our objective here is to employ a new robust and flexible tool for chromosome-wide analysis of X-linked markers in complex traits. Orofacial clefts are good candidates for such analysis because of the consistently observed excess of females with cleft palate only (CPO) and excess of males with cleft lip with or without cleft palate (CL/P).
methodsGenotypes for 14,486 X-chromosome SNPs in 1,291 Asian and 1,118 European isolated cleft triads were available from a previously published GWAS. The R-package HAPLIN enables genome-wide-level analyses as well as statistical power simulations for a range of biologic scenarios. We analyzed isolated CL/P and isolated CPO for each ethnicity in HAPLIN, using a sliding-window approach to haplotype analysis and two different statistical models, with and without X-inactivation in females.
resultsThere was a larger number of associations in the Asian versus the European sample, and similar to previous reports that have analyzed the same GWAS dataset using different methods, we identified associations with EFNB1/PJA1 and DMD. In addition, new associations were detected with several other genes, among which KLHL4, TBX22, CPXCR1 and BCOR were noteworthy because of their roles in clefting syndromes. A few of the associations were only detected by one particular X-inactivation model, whereas a few others were only detected in one sex. DISCUSSION/
conclusionWe found new support for the involvement of X-linked variants in isolated clefts. The associations were specific for ethnicity, sex and model parameterization, highlighting the need for flexible tools that are capable of detecting and estimating such effects. Further efforts are needed to verify and elucidate the potential roles of EFNB1/PJA1, KLHL4, TBX22, CPXCR1 and BCOR in isolated clefts.
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