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- Einarsdottir, E., et al.
(author)
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CELSR2 is a candidate susceptibility gene in idiopathic scoliosis
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Journal article (peer-reviewed)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.
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| 4. |
- Kou, I, et al.
(author)
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A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 11575-
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Journal article (peer-reviewed)abstract
- Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10−20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.
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| 5. |
- Ogura, Y, et al.
(author)
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An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4730-
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Journal article (peer-reviewed)abstract
- Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10−18 (odds ratio = 1.19, 95% confidence interval = 1.14–1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.
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| 9. |
- Diarbakerli, E., et al.
(author)
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Adults With Idiopathic Scoliosis Diagnosed at Youth Experience Similar Physical Activity and Fracture Rate as Controls
- 2017
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In: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436 .- 1528-1159. ; 42:7
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Journal article (peer-reviewed)abstract
- Study Design. Cross-sectional. Objective. To describe physical activity level and fracture rates in adults with idiopathic scoliosis, diagnosed before maturity, and to compare with a control group. Summary of Background Data. A previous study found a lower level of sporting activities in adults treated for idiopathic scoliosis compared with controls. Other studies have shown a lower bone mass in adults with idiopathic scoliosis compared with controls. Methods. One thousand two hundred seventy-eight adults (aged 18-71 yr) with idiopathic scoliosis and 214 controls (aged 18-70 yr) were included and answered the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and questions about previous fractures. The three scoliosis treatment groups (untreated n=360, brace n=460, and surgically treated n=458) were compared. Furthermore, a comparison based on onset (juvenile n=169 or adolescent n=976) was performed. Achieved weekly moderate activity level and metabolic equivalent task (MET) minutes/week were assessed for patients and controls. Statistical comparisons were made with analysis of covariance with adjustments for age, body mass index, and sex. Results. The proportion achieving weekly moderate activity level was 962 out of 1278 for individuals with idiopathic scoliosis (75%) and 157 out of 214 (73%) for controls (P=0.40). The scoliosis patients reported 2016MET-minutes/week (median value) and the controls 2456 (P=0.06). Fracture rates did not differ (P=0.72). Fewer surgically treated individuals achieved moderate activity level (P=0.046) compared with the untreated and the previously braced individuals. No difference was seen regarding MET-minutes/week (P=0.86). No differences were seen between individuals with a juvenile onset compared with individuals with an adolescent onset (all P >= 0.05). Conclusion. Adults with idiopathic scoliosis have similar physical activity level and do not sustain more fractures compared with controls. Adults with surgically treated idiopathic scoliosis have slightly lower physical activity level than previously braced and untreated patients. Onset of idiopathic scoliosis does not affect physical activity level.
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| 10. |
- Diarbakerli, E., et al.
(author)
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Health-Related Quality of Life in Adulthood in Untreated and Treated Individuals with Adolescent or Juvenile Idiopathic Scoliosis
- 2018
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In: Journal of Bone and Joint Surgery-American Volume. - : Ovid Technologies (Wolters Kluwer Health). - 0021-9355 .- 1535-1386. ; 100:10, s. 811-817
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Journal article (peer-reviewed)abstract
- Background: Health-related quality of life in adults with idiopathic scoliosis diagnosed before maturity has been reported to be similar between brace-treated and surgically treated individuals. The aim of this study was to compare health-related quality of life in untreated, brace-treated, and surgically treated adults with idiopathic scoliosis diagnosed before skeletal maturity. Subgroup analyses were performed on the basis of age at the time of the study, age of onset, surgical characteristics, and curve magnitude. Methods: We included 1,187 adults with juvenile or adolescent idiopathic scoliosis with a mean age (and standard deviation) of 38.8 +/- 12.7 years. Of these, 347 were untreated, 459 had been brace-treated, and 381 had been surgically treated. The Scoliosis Research Society-22r (SRS-22r) and EuroQol 5-Dimensions (EQ-5D) were used. Statistical analyses were performed using analysis of covariance. Results: The mean SRS-22r subscore was 4.15 +/- 0.59 points for the untreated group, 4.10 +/- 0.57 points for the previously braced group, and 4.01 +/- 0.64 points for the surgically treated group (p = 0.007 adjusted for age and sex). The EQ-5D index was 0.82 +/- 0.20 for the untreated group, 0.82 +/- 0.20 for the previously brace-treated group, and 0.79 +/- 0.24 for the surgically treated group (p = 0.026, adjusted for age and sex). Brace cessation was at the mean age of 16.2 +/- 1.5 years, and the surgical procedure had been performed at the mean age of 15.3 +/- 2.1 years. A more caudal fusion was associated with a lower SRS-22r subscore and EQ-5D index. No differences were observed when comparing individuals with juvenile or adolescent onset scoliosis (all p > 0.05). Conclusions: Untreated adults with idiopathic scoliosis had similar health-related quality of life to previously brace-treated individuals, and they had marginally higher health-related quality of life compared with surgically treated individuals. Therefore, both surgical and brace treatments for idiopathic scoliosis could be considered successful from a health-related quality-of-life point of view in adulthood. The age of onset of idiopathic scoliosis does not seem to influence quality of life in adulthood.
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