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

被引：96

作者：

Justice, Cristina M. ^{[2
]}

Yagnik, Garima ^{[1
]}

Kim, Yoonhee ^{[2
]}

Peter, Inga ^{[3
]}

Jabs, Ethylin Wang ^{[3
]}

Erazo, Monica ^{[3
]}

Ye, Xiaoqian ^{[3
]}

Ainehsazan, Edmond ^{[3
]}

Shi, Lisong ^{[3
]}

Cunningham, Michael L. ^{[4
,5
]}

Kimonis, Virginia ^{[6
]}

Roscioli, Tony ^{[7
]}

Wall, Steven A. ^{[8
]}

Wilkie, Andrew O. M. ^{[8
,9
]}

Stoler, Joan ^{[10
]}

Richtsmeier, Joan T. ^{[11
]}

Heuze, Yann ^{[11
]}

Sanchez-Lara, Pedro A. ^{[12
]}

Buckley, Michael F. ^{[13
]}

Druschel, Charlotte M. ^{[14
]}

Mills, James L. ^{[15
]}

Caggana, Michele ^{[16
]}

Romitti, Paul A. ^{[17
]}

Kay, Denise M. ^{[16
]}

Senders, Craig ^{[18
]}

Taub, Peter J. ^{[19
]}

Klein, Ophir D. ^{[20
,21
,22
]}

Boggan, James ^{[23
]}

Zwienenberg-Lee, Marike ^{[23
]}

Naydenov, Cyrill ^{[24
]}

Kim, Jinoh ^{[1
]}

Wilson, Alexander F. ^{[2
]}

Boyadjiev, Simeon A. ^{[1
]}

机构：

[1] Univ Calif Davis, Dept Pediat, Genet Sect, Sacramento, CA 95817 USA

[2] NHGRI, Genometr Sect, Inherited Dis Res Branch, Div Intramural Res,US Natl Inst Hlth NIH, Baltimore, MD USA

[3] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA

[4] Univ Washington, Dept Pediat, Div Craniofacial Med, Seattle, WA 98195 USA

[5] Seattle Childrens Res Inst, Seattle, WA USA

[6] Univ Calif Irvine, Dept Pediat, Div Genet, Irvine, CA 92717 USA

[7] Univ New S Wales, Sydney Childrens Hosp, Sch Womens & Childrens Hlth, Sydney, NSW, Australia

[8] John Radcliffe Hosp, Craniofacial Unit, Oxford Univ Hosp Natl Hlth Serv Trust, Oxford OX3 9DU, England

[9] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England

[10] Harvard Univ, Div Genet, Childrens Hosp Boston, Boston, MA 02115 USA

[11] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA

[12] Univ So Calif, Childrens Hosp Los Angeles, Dept Pathol & Pediat, Los Angeles, CA USA

[13] SE Area Lab Serv, Dept Haematol & Genet, Sydney, NSW, Australia

[14] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA

[15] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA

[16] New York State Dept Hlth, Div Genet, Wadsworth Ctr, Albany, NY USA

[17] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA

[18] Univ Calif Davis, Dept Otolaryngol, Sacramento, CA 95817 USA

[19] Mt Sinai Med Ctr, Kravis Childrens Hosp, Div Plast & Reconstruct Surg, New York, NY 10029 USA

[20] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA

[21] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA

[22] Univ Calif San Francisco, Program Craniofacial & Mesenchymal Biol, San Francisco, CA 94143 USA

[23] Univ Calif Davis, Dept Neurol Surg, Sacramento, CA 95817 USA

[24] Med Univ Sofia, Dept Chem & Biochem, Sofia, Bulgaria

来源：

NATURE GENETICS | 2012年 / 44卷 / 12期

基金：

英国惠康基金;

关键词：

TRANSCRIPTION FACTOR; PLASMA-MEMBRANE; GENETIC-BASIS; NEURAL CREST; MSX2; GENE; MUTATIONS; CILIA; TWIST; RISK; FAMILY;

D O I：

10.1038/ng.2463

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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 x 10(-14), odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 x 10(-11), OR = 0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 x 10(-10), OR = 0.19) and rs17724206 (P = 1.50 x 10(-8), OR = 0.22). We replicated the associations to both loci (rs1884302, P = 4.39 x 10(-31) and rs10262453, P= 3.50 x 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.

引用

页码：1360 / 1364

页数：5

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