A Genome-wide Association Study Identifies Susceptibility Loci for Nonsyndromic Sagittal Craniosynostosis Near BMP2 and Within BBS9

Overview

Journal Nat Genet

Specialty Genetics

Date 2012 Nov 20

PMID 23160099

Citations 67

Authors

Cristina M Justice

Garima Yagnik

Yoonhee Kim

Inga Peter

Ethylin Wang Jabs

Monica Erazo

Xiaoqian Ye

Edmond Ainehsazan

Lisong Shi

Michael L Cunningham

Virginia Kimonis

Tony Roscioli

Steven A Wall

Andrew O M Wilkie

Joan Stoler

Joan T Richtsmeier

Yann Heuze

Pedro A Sanchez-Lara

Michael F Buckley

Charlotte M Druschel

James L Mills

Michele Caggana

Paul A Romitti

Denise M Kay

Craig Senders

Peter J Taub

Ophir D Klein

James Boggan

Marike Zwienenberg-Lee

Cyrill Naydenov

Jinoh Kim

Alexander F Wilson

Simeon A Boyadjiev

Affiliations

Soon will be listed here.

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.

Citing Articles

Regulatory elements in (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits.

Nicoletti P, Zafer S, Matok L, Irron I, Patrick M, Haklai R Genet Med Open. 2024; 2.

PMID: 39345948 PMC: 11434253. DOI: 10.1016/j.gimo.2024.101851.

Reassessing the association: Evaluation of a polyalanine deletion variant of RUNX2 in non-syndromic sagittal and metopic craniosynostosis.

Walton I, McCann E, Weber A, Morton J, Noons P, Wilson L J Anat. 2024; 245(6):874-878.

PMID: 38760592 PMC: 11547237. DOI: 10.1111/joa.14052.

Whole genome sequencing identifies associations for nonsyndromic sagittal craniosynostosis with the intergenic region of BMP2 and noncoding RNA gene LINC01428.

Musolf A, Justice C, Erdogan-Yildirim Z, Goovaerts S, Cuellar A, Shaffer J Sci Rep. 2024; 14(1):8533.

PMID: 38609424 PMC: 11014861. DOI: 10.1038/s41598-024-58343-w.

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Transforming growth factor beta signaling and craniofacial development: modeling human diseases in zebrafish.

Fox S, Waskiewicz A Front Cell Dev Biol. 2024; 12:1338070.

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