CELSR2 is a candidate susceptibility gene in idiopathic scoliosis

Elisabet Einarsdottir, Anna Grauers, Jingwen Wang, Hong Jiao, Stefan A. Escher, Aina Danielsson, Ane Simony, Mikkel Andersen, Steen Bach Christensen, Kristina Åkesson, Ikuyo Kou, Anas M. Khanshour, Acke Ohlin, Carol Wise, Shiro Ikegawa, Juha Kere, Paul Gerdhem

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4 Citations (Scopus)

Abstract

A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c. G6859A change in exon 21 (NM_001408), leading to a predicted p.V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.

Original languageEnglish (US)
Article numbere0189591
JournalPLoS One
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

scoliosis
Scoliosis
Genes
Association reactions
Pedigree
pedigree
Proteolysis
genes
Chromosomes
Exome
penetrance
Genetic Linkage
Penetrance
Chromosomes, Human, Pair 1
Exons
automobiles
proteolysis
Haplotypes
exons
linkage (genetics)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Einarsdottir, E., Grauers, A., Wang, J., Jiao, H., Escher, S. A., Danielsson, A., ... Gerdhem, P. (2017). CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. PLoS One, 12(12), [e0189591]. https://doi.org/10.1371/journal.pone.0189591

CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. / Einarsdottir, Elisabet; Grauers, Anna; Wang, Jingwen; Jiao, Hong; Escher, Stefan A.; Danielsson, Aina; Simony, Ane; Andersen, Mikkel; Christensen, Steen Bach; Åkesson, Kristina; Kou, Ikuyo; Khanshour, Anas M.; Ohlin, Acke; Wise, Carol; Ikegawa, Shiro; Kere, Juha; Gerdhem, Paul.

In: PLoS One, Vol. 12, No. 12, e0189591, 01.12.2017.

Research output: Contribution to journalArticle

Einarsdottir, E, Grauers, A, Wang, J, Jiao, H, Escher, SA, Danielsson, A, Simony, A, Andersen, M, Christensen, SB, Åkesson, K, Kou, I, Khanshour, AM, Ohlin, A, Wise, C, Ikegawa, S, Kere, J & Gerdhem, P 2017, 'CELSR2 is a candidate susceptibility gene in idiopathic scoliosis', PLoS One, vol. 12, no. 12, e0189591. https://doi.org/10.1371/journal.pone.0189591
Einarsdottir E, Grauers A, Wang J, Jiao H, Escher SA, Danielsson A et al. CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. PLoS One. 2017 Dec 1;12(12). e0189591. https://doi.org/10.1371/journal.pone.0189591
Einarsdottir, Elisabet ; Grauers, Anna ; Wang, Jingwen ; Jiao, Hong ; Escher, Stefan A. ; Danielsson, Aina ; Simony, Ane ; Andersen, Mikkel ; Christensen, Steen Bach ; Åkesson, Kristina ; Kou, Ikuyo ; Khanshour, Anas M. ; Ohlin, Acke ; Wise, Carol ; Ikegawa, Shiro ; Kere, Juha ; Gerdhem, Paul. / CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. In: PLoS One. 2017 ; Vol. 12, No. 12.
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