A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9

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 Heuzé, Pedro A. Sanchez-Lara, Michael F. Buckley, Charlotte M. Druschel & 13 others James L. Mills, Michele Caggana, Paul A. Romitti, Denise M. Kay, Craig W Senders, Peter J. Taub, Ophir D. Klein, James E Boggan, Marike Zwienenberg-Lee, Cyrill Naydenov, Jinoh Kim, Alexander F. Wilson, Simeon Boyd

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1360-1364
Number of pages5
JournalNature Genetics
Volume44
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Craniosynostoses
Genome-Wide Association Study
Odds Ratio
Population
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9. / Justice, Cristina M.; Yagnik, Garima; Kim, Yoonhee; Peter, Inga; Jabs, Ethylin Wang; Erazo, Monica; Ye, Xiaoqian; Ainehsazan, Edmond; Shi, Lisong; Cunningham, Michael L.; Kimonis, Virginia; Roscioli, Tony; Wall, Steven A.; Wilkie, Andrew O M; Stoler, Joan; Richtsmeier, Joan T.; Heuzé, Yann; Sanchez-Lara, Pedro A.; Buckley, Michael F.; Druschel, Charlotte M.; Mills, James L.; Caggana, Michele; Romitti, Paul A.; Kay, Denise M.; Senders, Craig W; Taub, Peter J.; Klein, Ophir D.; Boggan, James E; Zwienenberg-Lee, Marike; Naydenov, Cyrill; Kim, Jinoh; Wilson, Alexander F.; Boyd, Simeon.

In: Nature Genetics, Vol. 44, No. 12, 12.2012, p. 1360-1364.

Research output: Contribution to journalArticle

Justice, CM, Yagnik, G, Kim, Y, Peter, I, Jabs, EW, Erazo, M, Ye, X, Ainehsazan, E, Shi, L, Cunningham, ML, Kimonis, V, Roscioli, T, Wall, SA, Wilkie, AOM, Stoler, J, Richtsmeier, JT, Heuzé, Y, Sanchez-Lara, PA, Buckley, MF, Druschel, CM, Mills, JL, Caggana, M, Romitti, PA, Kay, DM, Senders, CW, Taub, PJ, Klein, OD, Boggan, JE, Zwienenberg-Lee, M, Naydenov, C, Kim, J, Wilson, AF & Boyd, S 2012, 'A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9', Nature Genetics, vol. 44, no. 12, pp. 1360-1364. https://doi.org/10.1038/ng.2463
Justice, Cristina M. ; Yagnik, Garima ; Kim, Yoonhee ; Peter, Inga ; Jabs, Ethylin Wang ; Erazo, Monica ; Ye, Xiaoqian ; Ainehsazan, Edmond ; Shi, Lisong ; Cunningham, Michael L. ; Kimonis, Virginia ; Roscioli, Tony ; Wall, Steven A. ; Wilkie, Andrew O M ; Stoler, Joan ; Richtsmeier, Joan T. ; Heuzé, Yann ; Sanchez-Lara, Pedro A. ; Buckley, Michael F. ; Druschel, Charlotte M. ; Mills, James L. ; Caggana, Michele ; Romitti, Paul A. ; Kay, Denise M. ; Senders, Craig W ; Taub, Peter J. ; Klein, Ophir D. ; Boggan, James E ; Zwienenberg-Lee, Marike ; Naydenov, Cyrill ; Kim, Jinoh ; Wilson, Alexander F. ; Boyd, Simeon. / A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9. In: Nature Genetics. 2012 ; Vol. 44, No. 12. pp. 1360-1364.
@article{79045bbbaeef46b6bdd8f773398f1a04,
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.",
author = "Justice, {Cristina M.} and Garima Yagnik and Yoonhee Kim and Inga Peter and Jabs, {Ethylin Wang} and Monica Erazo and Xiaoqian Ye and Edmond Ainehsazan and Lisong Shi and Cunningham, {Michael L.} and Virginia Kimonis and Tony Roscioli and Wall, {Steven A.} and Wilkie, {Andrew O M} and Joan Stoler and Richtsmeier, {Joan T.} and Yann Heuz{\'e} and Sanchez-Lara, {Pedro A.} and Buckley, {Michael F.} and Druschel, {Charlotte M.} and Mills, {James L.} and Michele Caggana and Romitti, {Paul A.} and Kay, {Denise M.} and Senders, {Craig W} and Taub, {Peter J.} and Klein, {Ophir D.} and Boggan, {James E} and Marike Zwienenberg-Lee and Cyrill Naydenov and Jinoh Kim and Wilson, {Alexander F.} and Simeon Boyd",
year = "2012",
month = "12",
doi = "10.1038/ng.2463",
language = "English (US)",
volume = "44",
pages = "1360--1364",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9

AU - Justice, Cristina M.

AU - Yagnik, Garima

AU - Kim, Yoonhee

AU - Peter, Inga

AU - Jabs, Ethylin Wang

AU - Erazo, Monica

AU - Ye, Xiaoqian

AU - Ainehsazan, Edmond

AU - Shi, Lisong

AU - Cunningham, Michael L.

AU - Kimonis, Virginia

AU - Roscioli, Tony

AU - Wall, Steven A.

AU - Wilkie, Andrew O M

AU - Stoler, Joan

AU - Richtsmeier, Joan T.

AU - Heuzé, Yann

AU - Sanchez-Lara, Pedro A.

AU - Buckley, Michael F.

AU - Druschel, Charlotte M.

AU - Mills, James L.

AU - Caggana, Michele

AU - Romitti, Paul A.

AU - Kay, Denise M.

AU - Senders, Craig W

AU - Taub, Peter J.

AU - Klein, Ophir D.

AU - Boggan, James E

AU - Zwienenberg-Lee, Marike

AU - Naydenov, Cyrill

AU - Kim, Jinoh

AU - Wilson, Alexander F.

AU - Boyd, Simeon

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84870506995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870506995&partnerID=8YFLogxK

U2 - 10.1038/ng.2463

DO - 10.1038/ng.2463

M3 - Article

VL - 44

SP - 1360

EP - 1364

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 12

ER -