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GWAS Study

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

Justice CM, Yagnik G, Kim Y et al.

23160099 PubMed ID
GWAS Study Type
1110 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

JC
Justice CM
YG
Yagnik G
KY
Kim Y
PI
Peter I
JE
Jabs EW
EM
Erazo M
YX
Ye X
AE
Ainehsazan E
SL
Shi L
CM
Cunningham ML
KV
Kimonis V
RT
Roscioli T
WS
Wall SA
WA
Wilkie AO
SJ
Stoler J
RJ
Richtsmeier JT
HY
Heuzé Y
SP
Sanchez-Lara PA
BM
Buckley MF
DC
Druschel CM
MJ
Mills JL
CM
Caggana M
RP
Romitti PA
KD
Kay DM
SC
Senders C
TP
Taub PJ
KO
Klein OD
BJ
Boggan J
ZM
Zwienenberg-Lee M
NC
Naydenov C
KJ
Kim J
WA
Wilson AF
BS
Boyadjiev SA
Chapter II

Abstract

Summary of the research findings

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.

130 European ancestry trios

Chapter III

Study Statistics

Key metrics and study information

1110
Total Participants
GWAS
Study Type
Yes
Replicated
172 cases, 548 controls
Replication Participants
European
Ancestry
U.S.
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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