Evidence that TGFA influences risk to cleft lip with/without cleft palate through unconventional genetic mechanisms

Jae Woong Sull, Kung Yee Liang, Jacqueline B. Hetmanski, Tao Wu, Margaret Daniele Fallin, Roxann G. Ingersoll, Ji Wan Park, Yah Huei Wu-Chou, Philip K. Chen, Samuel S. Chong, Felicia Cheah, Vincent Yeow, Beyoung Yun Park, Sun Ha Jee, Ethylin Wang Jabs, Richard Redett, Alan F. Scott, Terri H. Beaty

Research output: Contribution to journalArticle

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Abstract

This study examined the association between markers in transforming growth factor alpha (TGFA) and isolated, non-syndromic cleft lip with/ without palate (CL/P) using a case-parent trio design, considering parent-of-origin effects. We also tested for gene-environmental interaction with common maternal exposures, and for gene-gene interaction using markers in TGFA and another recognized causal gene, IRF6. CL/P case-parent trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 17 single nucleotide polymorphisms (SNPs) in TGFA. The transmission disequilibrium test was used to test individual SNPs, and the parent-of-origin likelihood ratio test (PO-LRT) was used to assess parent-of-origin effects. We also screened for possible gene-environment interaction using PBAT, and tested for gene-gene interaction using conditional logistic regression models. When all trios were combined, four SNPs showed significant excess maternal transmission, two of which gave significant PO-LRT values [rs3821261: P = 0.004 and OR(imprinting) = 4.17; and rs3771475: P = 0.027 and OR(imprinting) = 2.44]. Haplotype analysis of these two SNPS also supported excess maternal transmission. We saw intriguing but suggestive evidence of G × E interaction for several SNPs in TGFA when either individual SNPs or haplotypes of adjacent SNPs were considered. Thus, TGFA appears to influence risk of CL/P through unconventional means with an apparent parent-of-origin effect (excess maternal transmission) and possible interaction with maternal exposures.

Original languageEnglish
Pages (from-to)385-394
Number of pages10
JournalHuman Genetics
Volume126
Issue number3
DOIs
Publication statusPublished - May 15 2009
Externally publishedYes

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Transforming Growth Factor alpha
Cleft Lip
Cleft Palate
Single Nucleotide Polymorphism
Palate
Genes
Maternal Exposure
Mothers
Haplotypes
Logistic Models
Gene-Environment Interaction
Singapore
Korea
Taiwan
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Sull, J. W., Liang, K. Y., Hetmanski, J. B., Wu, T., Fallin, M. D., Ingersoll, R. G., ... Beaty, T. H. (2009). Evidence that TGFA influences risk to cleft lip with/without cleft palate through unconventional genetic mechanisms. Human Genetics, 126(3), 385-394. https://doi.org/10.1007/s00439-009-0680-3

Evidence that TGFA influences risk to cleft lip with/without cleft palate through unconventional genetic mechanisms. / Sull, Jae Woong; Liang, Kung Yee; Hetmanski, Jacqueline B.; Wu, Tao; Fallin, Margaret Daniele; Ingersoll, Roxann G.; Park, Ji Wan; Wu-Chou, Yah Huei; Chen, Philip K.; Chong, Samuel S.; Cheah, Felicia; Yeow, Vincent; Park, Beyoung Yun; Jee, Sun Ha; Jabs, Ethylin Wang; Redett, Richard; Scott, Alan F.; Beaty, Terri H.

In: Human Genetics, Vol. 126, No. 3, 15.05.2009, p. 385-394.

Research output: Contribution to journalArticle

Sull, JW, Liang, KY, Hetmanski, JB, Wu, T, Fallin, MD, Ingersoll, RG, Park, JW, Wu-Chou, YH, Chen, PK, Chong, SS, Cheah, F, Yeow, V, Park, BY, Jee, SH, Jabs, EW, Redett, R, Scott, AF & Beaty, TH 2009, 'Evidence that TGFA influences risk to cleft lip with/without cleft palate through unconventional genetic mechanisms', Human Genetics, vol. 126, no. 3, pp. 385-394. https://doi.org/10.1007/s00439-009-0680-3
Sull, Jae Woong ; Liang, Kung Yee ; Hetmanski, Jacqueline B. ; Wu, Tao ; Fallin, Margaret Daniele ; Ingersoll, Roxann G. ; Park, Ji Wan ; Wu-Chou, Yah Huei ; Chen, Philip K. ; Chong, Samuel S. ; Cheah, Felicia ; Yeow, Vincent ; Park, Beyoung Yun ; Jee, Sun Ha ; Jabs, Ethylin Wang ; Redett, Richard ; Scott, Alan F. ; Beaty, Terri H. / Evidence that TGFA influences risk to cleft lip with/without cleft palate through unconventional genetic mechanisms. In: Human Genetics. 2009 ; Vol. 126, No. 3. pp. 385-394.
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AU - Fallin, Margaret Daniele

AU - Ingersoll, Roxann G.

AU - Park, Ji Wan

AU - Wu-Chou, Yah Huei

AU - Chen, Philip K.

AU - Chong, Samuel S.

AU - Cheah, Felicia

AU - Yeow, Vincent

AU - Park, Beyoung Yun

AU - Jee, Sun Ha

AU - Jabs, Ethylin Wang

AU - Redett, Richard

AU - Scott, Alan F.

AU - Beaty, Terri H.

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