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; 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; Andrew 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

doi:10.1038/ng.580

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

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, Andrew 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

Johns Hopkins University
University of Iowa
University of Pittsburgh
Utah State University
Peking University
National Institutes of Health
University of Bergen
Icahn School of Medicine at Mount Sinai
Chang Gung Memorial Hospital
Wuhan University
Chinese Academy of Medical Sciences
KK Women's and Children's Hospital
National University of Singapore
Yonsei University
Sichuan University
University of Southern Denmark
Statens Serum Institut
Fundação Oswaldo Cruz
Foundation for Community Control of Hereditary Diseases
University of British Columbia
Trinity College Dublin
Health Research Board Ireland
University of Miami

Research output: Contribution to journal › Journal Article › peer-review

506 Scopus citations

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 language	English
Pages (from-to)	525-529
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	6
DOIs	https://doi.org/10.1038/ng.580
State	Published - 06 2010
Externally published	Yes

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Beaty, T. H., Murray, J. C., Marazita, M. L., Munger, R. G., Ruczinski, I., Hetmanski, J. B., Liang, K. Y., Wu, T., Murray, T., Fallin, M. D., Redett, R. A., Raymond, G., Schwender, H., Jin, S. C., Cooper, M. E., Dunnwald, M., Mansilla, M. A., Leslie, E., Bullard, S., ... 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

@article{5a424595a0634dd29e768ea5927fd3f9,

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

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 {\texttimes} 10-11; and ABCA4, most significant SNP rs560426, with OR = 1.432, 95\% CI 1.292-1.587, P = 5.01 {\texttimes} 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.",

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

year = "2010",

month = jun,

doi = "10.1038/ng.580",

language = "英语",

volume = "42",

pages = "525--529",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "6",

}

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, AE, 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

TY - JOUR

T1 - A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

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.

AU - Raymond, Gerald

AU - Schwender, Holger

AU - Jin, Sheng Chih

AU - Cooper, Margaret E.

AU - Dunnwald, Martine

AU - Mansilla, Maria A.

AU - Leslie, Elizabeth

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, Andrew 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.

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/77952886672

U2 - 10.1038/ng.580

DO - 10.1038/ng.580

M3 - 文章

C2 - 20436469

AN - SCOPUS:77952886672

SN - 1061-4036

VL - 42

SP - 525

EP - 529

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

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

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