A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

Terri H. Beaty, Jeffrey C. Murray, Mary L. Marazita, Ronald G. Munger, Ingo Ruczinski, Jacqueline B. Hetmanski, Kung Yee Liang, Tao Wu, Tanda Murray, M. Daniele Fallin, Richard A. Redett, Gerald Raymond, Holger Schwender, Sheng Chih Jin, Margaret E. Cooper, Martine Dunnwald, Maria A. Mansilla, Elizabeth Leslie, Stephen Bullard, Andrew C. Lidral & 33 others Lina M. Moreno, Renato Menezes, Alexandre R. Vieira, Aline Petrin, Allen J. Wilcox, Rolv T. Lie, Ethylin W. Jabs, Yah Huei Wu-Chou, Philip K. Chen, Hong Wang, Xiaoqian Ye, Shangzhi Huang, Vincent Yeow, Samuel S. Chong, Sun Ha Jee, Bing Shi, Kaare Christensen, Mads Melbye, Kimberly F. Doheny, Elizabeth W. Pugh, Hua Ling, Eduardo E. Castilla, E. Czeizel, Lian Ma, L. Leigh Field, Lawrence Brody, Faith Pangilinan, James L. Mills, Anne M. Molloy, Peadar N. Kirke, James M. Scott, Mauricio Arcos-Burgos, Alan F. Scott

Research output: Contribution to journalArticle

322 Citations (Scopus)

Abstract

Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 × 10-11; and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 × 10-12) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development.

Original languageEnglish
Pages (from-to)525-529
Number of pages5
JournalNature Genetics
Volume42
Issue number6
DOIs
Publication statusPublished - Jun 2010

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Cleft Lip
Genome-Wide Association Study
Cleft Palate
Single Nucleotide Polymorphism
Odds Ratio
Chromosomes
Alleles
Genome
Population
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Beaty, T. H., Murray, J. C., Marazita, M. L., Munger, R. G., Ruczinski, I., Hetmanski, J. B., ... Scott, A. F. (2010). A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nature Genetics, 42(6), 525-529. https://doi.org/10.1038/ng.580

A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. / Beaty, Terri H.; Murray, Jeffrey C.; Marazita, Mary L.; Munger, Ronald G.; Ruczinski, Ingo; Hetmanski, Jacqueline B.; Liang, Kung Yee; Wu, Tao; Murray, Tanda; Fallin, M. Daniele; Redett, Richard A.; Raymond, Gerald; Schwender, Holger; Jin, Sheng Chih; Cooper, Margaret E.; Dunnwald, Martine; Mansilla, Maria A.; Leslie, Elizabeth; Bullard, Stephen; Lidral, Andrew C.; Moreno, Lina M.; Menezes, Renato; Vieira, Alexandre R.; Petrin, Aline; Wilcox, Allen J.; Lie, Rolv T.; Jabs, Ethylin W.; Wu-Chou, Yah Huei; Chen, Philip K.; Wang, Hong; Ye, Xiaoqian; Huang, Shangzhi; Yeow, Vincent; Chong, Samuel S.; Jee, Sun Ha; Shi, Bing; Christensen, Kaare; Melbye, Mads; Doheny, Kimberly F.; Pugh, Elizabeth W.; Ling, Hua; Castilla, Eduardo E.; Czeizel, E.; Ma, Lian; Field, L. Leigh; Brody, Lawrence; Pangilinan, Faith; Mills, James L.; Molloy, Anne M.; Kirke, Peadar N.; Scott, James M.; Arcos-Burgos, Mauricio; Scott, Alan F.

In: Nature Genetics, Vol. 42, No. 6, 06.2010, p. 525-529.

Research output: Contribution to journalArticle

Beaty, TH, Murray, JC, Marazita, ML, Munger, RG, Ruczinski, I, Hetmanski, JB, Liang, KY, Wu, T, Murray, T, Fallin, MD, Redett, RA, Raymond, G, Schwender, H, Jin, SC, Cooper, ME, Dunnwald, M, Mansilla, MA, Leslie, E, Bullard, S, Lidral, AC, Moreno, LM, Menezes, R, Vieira, AR, Petrin, A, Wilcox, AJ, Lie, RT, Jabs, EW, Wu-Chou, YH, Chen, PK, Wang, H, Ye, X, Huang, S, Yeow, V, Chong, SS, Jee, SH, Shi, B, Christensen, K, Melbye, M, Doheny, KF, Pugh, EW, Ling, H, Castilla, EE, Czeizel, E, Ma, L, Field, LL, Brody, L, Pangilinan, F, Mills, JL, Molloy, AM, Kirke, PN, Scott, JM, Arcos-Burgos, M & Scott, AF 2010, 'A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4', Nature Genetics, vol. 42, no. 6, pp. 525-529. https://doi.org/10.1038/ng.580
Beaty, Terri H. ; Murray, Jeffrey C. ; Marazita, Mary L. ; Munger, Ronald G. ; Ruczinski, Ingo ; Hetmanski, Jacqueline B. ; Liang, Kung Yee ; Wu, Tao ; Murray, Tanda ; Fallin, M. Daniele ; Redett, Richard A. ; Raymond, Gerald ; Schwender, Holger ; Jin, Sheng Chih ; Cooper, Margaret E. ; Dunnwald, Martine ; Mansilla, Maria A. ; Leslie, Elizabeth ; Bullard, Stephen ; Lidral, Andrew C. ; Moreno, Lina M. ; Menezes, Renato ; Vieira, Alexandre R. ; Petrin, Aline ; Wilcox, Allen J. ; Lie, Rolv T. ; Jabs, Ethylin W. ; Wu-Chou, Yah Huei ; Chen, Philip K. ; Wang, Hong ; Ye, Xiaoqian ; Huang, Shangzhi ; Yeow, Vincent ; Chong, Samuel S. ; Jee, Sun Ha ; Shi, Bing ; Christensen, Kaare ; Melbye, Mads ; Doheny, Kimberly F. ; Pugh, Elizabeth W. ; Ling, Hua ; Castilla, Eduardo E. ; Czeizel, E. ; Ma, Lian ; Field, L. Leigh ; Brody, Lawrence ; Pangilinan, Faith ; Mills, James L. ; Molloy, Anne M. ; Kirke, Peadar N. ; Scott, James M. ; Arcos-Burgos, Mauricio ; Scott, Alan F. / A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. In: Nature Genetics. 2010 ; Vol. 42, No. 6. pp. 525-529.
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abstract = "Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95{\%} CI 0.635-0.778, P = 1.44 × 10-11; and ABCA4, most significant SNP rs560426, with OR = 1.432, 95{\%} CI 1.292-1.587, P = 5.01 × 10-12) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development.",
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AU - Beaty, Terri H.

AU - Murray, Jeffrey C.

AU - Marazita, Mary L.

AU - Munger, Ronald G.

AU - Ruczinski, Ingo

AU - Hetmanski, Jacqueline B.

AU - Liang, Kung Yee

AU - Wu, Tao

AU - Murray, Tanda

AU - Fallin, M. Daniele

AU - Redett, Richard A.

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AU - Dunnwald, Martine

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AU - Bullard, Stephen

AU - Lidral, Andrew C.

AU - Moreno, Lina M.

AU - Menezes, Renato

AU - Vieira, Alexandre R.

AU - Petrin, Aline

AU - Wilcox, Allen J.

AU - Lie, Rolv T.

AU - Jabs, Ethylin W.

AU - Wu-Chou, Yah Huei

AU - Chen, Philip K.

AU - Wang, Hong

AU - Ye, Xiaoqian

AU - Huang, Shangzhi

AU - Yeow, Vincent

AU - Chong, Samuel S.

AU - Jee, Sun Ha

AU - Shi, Bing

AU - Christensen, Kaare

AU - Melbye, Mads

AU - Doheny, Kimberly F.

AU - Pugh, Elizabeth W.

AU - Ling, Hua

AU - Castilla, Eduardo E.

AU - Czeizel, E.

AU - Ma, Lian

AU - Field, L. Leigh

AU - Brody, Lawrence

AU - Pangilinan, Faith

AU - Mills, James L.

AU - Molloy, Anne M.

AU - Kirke, Peadar N.

AU - Scott, James M.

AU - Arcos-Burgos, Mauricio

AU - Scott, Alan F.

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