ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population

Hong Wang, Jacqueline B. Hetmanski, Ingo Ruczinski, Kung Yee Liang, M. Daniele Fallin, Richard J. Redett, Gerald V. Raymond, Yah Huei Wu Chou, Philip Kuo Ting Chen, Vincent Yeow, Samuel S. Chong, Felicia S.H. Cheah, Ethylin Wang Jabs, Alan F. Scott, Terri H. Beaty

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: The receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans. The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts. Methods: Here we tested 38 eligible single-nucleotide polymorphisms (SNPs) in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland. Family Based Association Test was used to test for deviation from Mendelian inheritance. Plink software was used to test potential parent of origin effect. Possible maternally mediated in utero effects were assessed using the TRIad Multi-Marker approach under an assumption of mating symmetry in the population. Results: Significant evidence of linkage and association was shown for 3 SNPs (rs7858435, rs10820914 and rs3905385) among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests. P values for these 3 SNPs equaled to 0.000068, 0.000115 and 0.000464 respectively which were all less than the significance level (0.05/38=0.0013) adjusted by strict Bonferroni correction. Relevant odds ratios for the risk allele were 3.42 (1.80-6.50), 3.45 (1.75-6.67) and 2.94 (1.56-5.56), respectively. Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate. Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups. Conclusion: Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.

Original languageEnglish
Pages (from-to)476-480
Number of pages5
JournalChinese Medical Journal
Volume125
Issue number3
DOIs
Publication statusPublished - Feb 5 2012
Externally publishedYes

Fingerprint

Cleft Palate
Population
Genes
Single Nucleotide Polymorphism
Cleft Lip
Receptor Tyrosine Kinase-like Orphan Receptors
Software
Animal Models
Alleles
Odds Ratio

Keywords

  • Association
  • Cleft lip
  • Cleft palate
  • Receptor tyrosine kinase-like orphan receptor 2
  • Transmission disequilibrium test

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wang, H., Hetmanski, J. B., Ruczinski, I., Liang, K. Y., Daniele Fallin, M., Redett, R. J., ... Beaty, T. H. (2012). ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population. Chinese Medical Journal, 125(3), 476-480. https://doi.org/10.3760/cma.j.issn.0366-6999.2012.03.014

ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population. / Wang, Hong; Hetmanski, Jacqueline B.; Ruczinski, Ingo; Liang, Kung Yee; Daniele Fallin, M.; Redett, Richard J.; Raymond, Gerald V.; Wu Chou, Yah Huei; Chen, Philip Kuo Ting; Yeow, Vincent; Chong, Samuel S.; Cheah, Felicia S.H.; Jabs, Ethylin Wang; Scott, Alan F.; Beaty, Terri H.

In: Chinese Medical Journal, Vol. 125, No. 3, 05.02.2012, p. 476-480.

Research output: Contribution to journalArticle

Wang, H, Hetmanski, JB, Ruczinski, I, Liang, KY, Daniele Fallin, M, Redett, RJ, Raymond, GV, Wu Chou, YH, Chen, PKT, Yeow, V, Chong, SS, Cheah, FSH, Jabs, EW, Scott, AF & Beaty, TH 2012, 'ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population', Chinese Medical Journal, vol. 125, no. 3, pp. 476-480. https://doi.org/10.3760/cma.j.issn.0366-6999.2012.03.014
Wang H, Hetmanski JB, Ruczinski I, Liang KY, Daniele Fallin M, Redett RJ et al. ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population. Chinese Medical Journal. 2012 Feb 5;125(3):476-480. https://doi.org/10.3760/cma.j.issn.0366-6999.2012.03.014
Wang, Hong ; Hetmanski, Jacqueline B. ; Ruczinski, Ingo ; Liang, Kung Yee ; Daniele Fallin, M. ; Redett, Richard J. ; Raymond, Gerald V. ; Wu Chou, Yah Huei ; Chen, Philip Kuo Ting ; Yeow, Vincent ; Chong, Samuel S. ; Cheah, Felicia S.H. ; Jabs, Ethylin Wang ; Scott, Alan F. ; Beaty, Terri H. / ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population. In: Chinese Medical Journal. 2012 ; Vol. 125, No. 3. pp. 476-480.
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AU - Wang, Hong

AU - Hetmanski, Jacqueline B.

AU - Ruczinski, Ingo

AU - Liang, Kung Yee

AU - Daniele Fallin, M.

AU - Redett, Richard J.

AU - Raymond, Gerald V.

AU - Wu Chou, Yah Huei

AU - Chen, Philip Kuo Ting

AU - Yeow, Vincent

AU - Chong, Samuel S.

AU - Cheah, Felicia S.H.

AU - Jabs, Ethylin Wang

AU - Scott, Alan F.

AU - Beaty, Terri H.

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N2 - Background: The receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans. The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts. Methods: Here we tested 38 eligible single-nucleotide polymorphisms (SNPs) in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland. Family Based Association Test was used to test for deviation from Mendelian inheritance. Plink software was used to test potential parent of origin effect. Possible maternally mediated in utero effects were assessed using the TRIad Multi-Marker approach under an assumption of mating symmetry in the population. Results: Significant evidence of linkage and association was shown for 3 SNPs (rs7858435, rs10820914 and rs3905385) among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests. P values for these 3 SNPs equaled to 0.000068, 0.000115 and 0.000464 respectively which were all less than the significance level (0.05/38=0.0013) adjusted by strict Bonferroni correction. Relevant odds ratios for the risk allele were 3.42 (1.80-6.50), 3.45 (1.75-6.67) and 2.94 (1.56-5.56), respectively. Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate. Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups. Conclusion: Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.

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