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 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 x 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.
authors.affiliation: Johns Hopkins University, School of Public Health, Baltimore, Maryland, USA. tbeaty@jhsph.edu
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Munger
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Kung Yee
authors.initials: KY
authors.lastname: Liang
authors.forename: Tao
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authors.lastname: Wu
authors.forename: Tanda
authors.initials: T
authors.lastname: Murray
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.forename: Richard A
authors.initials: RA
authors.lastname: Redett
authors.forename: Gerald
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authors.lastname: Raymond
authors.forename: Holger
authors.initials: H
authors.lastname: Schwender
authors.forename: Sheng-Chih
authors.initials: SC
authors.lastname: Jin
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Martine
authors.initials: M
authors.lastname: Dunnwald
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mansilla
authors.forename: Elizabeth
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authors.lastname: Leslie
authors.forename: Stephen
authors.initials: S
authors.lastname: Bullard
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Lidral
authors.forename: Lina M
authors.initials: LM
authors.lastname: Moreno
authors.forename: Renato
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authors.lastname: Menezes
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
authors.forename: Aline
authors.initials: A
authors.lastname: Petrin
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Wilcox
authors.forename: Rolv T
authors.initials: RT
authors.lastname: Lie
authors.forename: Ethylin W
authors.initials: EW
authors.lastname: Jabs
authors.forename: Yah Huei
authors.initials: YH
authors.lastname: Wu-Chou
authors.forename: Philip K
authors.initials: PK
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ye
authors.forename: Shangzhi
authors.initials: S
authors.lastname: Huang
authors.forename: Vincent
authors.initials: V
authors.lastname: Yeow
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Chong
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Pugh
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castilla
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Czeizel
authors.forename: Lian
authors.initials: L
authors.lastname: Ma
authors.forename: L Leigh
authors.initials: LL
authors.lastname: Field
authors.forename: Lawrence
authors.initials: L
authors.lastname: Brody
authors.forename: Faith
authors.initials: F
authors.lastname: Pangilinan
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: James M
authors.initials: JM
authors.lastname: Scott
authors.forename: Mauricio
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authors.lastname: Arcos-Burgos
authors.forename: Alan F
authors.initials: AF
authors.lastname: Scott
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D044466:Asian People / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051258:MafB Transcription Factor / Q000235:genetics*; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C490407:MAFB protein, human; D051258:MafB Transcription Factor