title: A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9.
abstract: Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations in a 120-kb region downstream of BMP2 flanked by rs1884302 (P = 1.13 × 10(-14), odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 × 10(-11), OR = 0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 × 10(-10), OR = 0.19) and rs17724206 (P = 1.50 × 10(-8), OR = 0.22). We replicated the associations to both loci (rs1884302, P = 4.39 × 10(-31) and rs10262453, P = 3.50 × 10(-14)) in an independent NHW population of 172 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC.
authors.affiliation: Genometrics Section, Inherited Disease Research Branch, Division of Intramural Research, National Human Genome Research Institute, US National Institutes of Health (NIH), Baltimore, MD, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Justice
authors.forename: Garima
authors.initials: G
authors.lastname: Yagnik
authors.forename: Yoonhee
authors.initials: Y
authors.lastname: Kim
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.forename: Monica
authors.initials: M
authors.lastname: Erazo
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ye
authors.forename: Edmond
authors.initials: E
authors.lastname: Ainehsazan
authors.forename: Lisong
authors.initials: L
authors.lastname: Shi
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cunningham
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
authors.forename: Tony
authors.initials: T
authors.lastname: Roscioli
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wall
authors.forename: Andrew O M
authors.initials: AO
authors.lastname: Wilkie
authors.forename: Joan
authors.initials: J
authors.lastname: Stoler
authors.forename: Joan T
authors.initials: JT
authors.lastname: Richtsmeier
authors.forename: Yann
authors.initials: Y
authors.lastname: Heuzé
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Sanchez-Lara
authors.forename: Michael F
authors.initials: MF
authors.lastname: Buckley
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Druschel
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
authors.forename: Paul A
authors.initials: PA
authors.lastname: Romitti
authors.forename: Denise M
authors.initials: DM
authors.lastname: Kay
authors.forename: Craig
authors.initials: C
authors.lastname: Senders
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Taub
authors.forename: Ophir D
authors.initials: OD
authors.lastname: Klein
authors.forename: James
authors.initials: J
authors.lastname: Boggan
authors.forename: Marike
authors.initials: M
authors.lastname: Zwienenberg-Lee
authors.forename: Cyrill
authors.initials: C
authors.lastname: Naydenov
authors.forename: Jinoh
authors.initials: J
authors.lastname: Kim
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Wilson
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D015331:Cohort Studies; D003398:Craniosynostoses / Q000235:genetics*; D003598:Cytoskeletal Proteins; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D044465:White People / Q000235:genetics
chemical_list: C472639:BBS9 protein, human; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins