A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24

Grant, Struan F.A.; Wang, Kai; Zhang, Haitao; Glaberson, Wendy; Annaiah, Kiran; Kim, Chong; Bradfield, Jonathan P.; Glessner, Joseph T.; Thomas, Kelly; Garris, Maria; Frackelton, Edward C.; Otieno, F. George; Chiavacci, Rosetta M.; Nah, Hyun-Duck; Kirschner, Richard E.; Hákonarson, Hákon

doi:10.1016/j.jpeds.2009.06.020

Cited by 249 publications

(253 citation statements)

References 24 publications

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“…Recent studies have reported association of nsCL/P with many loci throughout the genome [11][12][13][14][39][40][41][42] . Replication of those results on various populations and the investigation of mechanisms by which these variants influence cleft susceptibility are crucial for better understanding of genetic architecture of nsCL/P.…”

Section: Resultsmentioning

confidence: 99%

“…The GWAS in Europeans also identified one of the most robust nsCL/P susceptibility loci at chromosome 8q24 (ref. [11][12][13] ), principally tagged by SNP rs987525. Additional significant GWAS signals in the European populations 14 were detected at loci 10q25 and 17q22, SNPs rs7078160 at 10q25 and rs227731 at 17q22 being the strongest susceptibility markers.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Salagovic¹,

Klimčáková²,

Zabavnikova³

et al. 2017

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is the most common orofacial birth defect with an aetiology involving both genetic and environmental factors. Genome-wide association studies (GWAS) have identified several genomic susceptibility regions for nsCL/P. In the present study, the three well established single nucleotide polymorphisms (SNPs) identified by GWAS (rs987525 at 8q24, rs7078160 at 10q25, and rs227731 at 17q22 loci) and one SNP identified by candidate gene study (rs642961 in IRF6 gene at 1q32 locus) were analysed for an association with nsCL/P in Slovak population. Methods. Nucleotide variants were genotyped in 165 nsCL/P patients and 326 unaffected controls. All variants of interest were genotyped using high-resolution melting analysis after real-time PCR. Results. We found significant differences between patient and control groups with respect to the allele and genotype frequencies for the SNPs at the 1q32, 8q24, and 17q22 loci. SNP at the 10q25 locus showed a trend toward association with nsCL/P risk. Conclusions.The results suggest that SNPs at the 1q32, 8q24 and 17q22 loci may contribute to the nsCL/P risk in Slovak population.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Salagovic¹,

Klimčáková²,

Zabavnikova³

et al. 2017

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…There are four published genome-wide association (GWA) studies, three using a casecontrol design (Birnbaum et al, 2009;Grant et al, 2009;Mangold et al, 2010) and one using a case-parent trio design (Beaty et al, 2010), for NSCL/P. These studies confirmed the impact of IRF6, discovered a new region on chromosome 8q24, and identified two new loci (MAFB and ABCA4) associated with NSCL/P.…”

Section: Introductionmentioning

confidence: 95%

Variations in WNT3 gene are associated with incidence of non-syndromic cleft lip with or without cleft palate in a northeast Chinese population

Yp¹,

Wt²,

Q³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect. Several WNT genes are involved in craniofacial embryogenesis, and therefore may play an important role in the etiology of NSCL/P. Two SNPs (rs3809857 and rs9890413) in the WNT3 gene were subjected to case-control and case-parent analysis by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 236 unrelated patients with NSCL/P, including 128 elementary families (185 mothers and 154 fathers), and 400 control individuals from northeast China. The rs3809857 SNP, under the assumption of a dominant model, was found to induce a 2-fold lower risk of NSCL/P OR GG vs GT + TT = 0.605, 95%CI = 0.436-0.839, P = 0.003). Moreover, the family-based association test revealed an under- 12647Variations in WNT3 are associated with orofacial clefts ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 12646-12653 (2015) transmission for the minor allele T. On the other hand, we observed a significant association in the case-control and case-parent analysis of the SNP rs9890413. In addition, the P values for the haplotype of rs3809857-rs9890413 were observed to be statistically significant (P = 0.004). In conclusion, our study confirmed the association between the WNT3 variant and NSCL/P in the population tested.

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“…Several more GWAS studies of these oral health outcomes, plus periodontal disease, dental fear, and saliva flow rate, are currently under way. Notable associations for oral health outcomes include the PVT1/GSDMC locus on chromosome 8q24, which was independently identified in three GWAS studies of non-syndromic cleft lip with or without cleft palate (CL/P; Birnbaum et al, 2009;Grant et al, 2009;Beaty et al, Poor-quality DNA samples may need to be recollected and/or replaced. (F) Substantial data cleaning, quality checking, and pre-processing are necessary, including rigorous investigations of the following items: SNP call rates to identify/exclude poorly genotyped variants, genotype batch effects to detect genotyping artifacts, Hardy-Weinberg equilibrium to identify poorly performing SNPs, relationship testing to verify known kinships and detect cryptic kinships, gender tests to help identify sample swaps, and tests for "connectivity" to identify sample contamination.…”

Section: Understanding Gwasmentioning

confidence: 99%

Genome-wide Association Studies

2012

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The genomic era of biomedical research has given rise to the genome-wide association study (GWAS) approach, which attempts to discover novel genes affecting an outcome by testing a large number (i.e., hundreds of thousands to millions) of genetic variants for association. This article discusses the issues surrounding the GWAS approach with emphasis on the prospects and challenges relevant to the oral health research community.

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A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24

Cited by 249 publications

References 24 publications

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Variations in WNT3 gene are associated with incidence of non-syndromic cleft lip with or without cleft palate in a northeast Chinese population

Genome-wide Association Studies

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