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Thread: Scoliscore Fails Second, Independent Analysis

  1. #1
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    Scoliscore Fails Second, Independent Analysis

    A few weeks ago Scoliscore failed for the second time when put under independent analysis. First here is some quick background information. Axial Biotech, the company that developed this test was liquidated in 2013. The company website is currently being used to sell E-Cigarettes. Dr. Kenneth Ward, Axial's Chief Scientific Officer no longer works in the field of Scoliosis. ScoliScore was purchased by a penny stock company called Transgenomic during the liquidation.

    A Replication Study for Association of 53 Single Nucleotide Polymorphisms in ScoliScoreTM Test with Adolescent Idiopathic Scoliosis in French-Canadian Population.
    Spine (Phila Pa 1976). 2015 Feb 2.

    STRUCTURED ABSTRACT:
    Study Design. A replication association study that used genomic data generated from French-Canadian case and control cohorts.Objectives. To determine whether the 53 single nucleotide polymorphisms (SNPs) that were previously associated with spinal deformity progression in an American Caucasian cohort, are similarly associated in French-Canadian population.Summary of Background Data. It is widely accepted that genetic factors contribute to AIS. The identification of genetic variants associated with the predisposition or progression of curvature could facilitate diagnostic/prognostic tool development. Although 53 SNPs have been associated with spinal curve progression in Caucasian cohorts in the USA, these associations were not replicated in a large Japanese-population study, arguing that such a discrepancy could be explained by ethnicity, thus raising the importance of a replication study in an independent Caucasian population of European descent.Methods. Genomic data was collected from the French-Canadian population, using the Illumina HumanOmni 2.5M BeadChip. Fifty-two SNPs, tested in ScoliScore or in high linkage disequilibrium (LD) with SNPs in the test, were selected to assess their association with scoliosis generally, and with spinal curve progression. One SNP in ScoliScore, rs16909285, could not be evaluated in our GWAS.Results. None of the SNPs used in ScoliScore were associated with AIS curve progression or curve occurrence in French-Canadian population. We evaluated 52 SNPs in severe patients by comparing risk allele frequencies with those in non-severe patients and with those in control individuals. There was no significant difference between the severe group and the non-severe group or between the severe group and the control group.Conclusions. Although the 52 SNPs studied here were previously associated with curve progression in an American population of European descent, we found no association in French-Canadian AIS patients. This second replication cohort suggests that the lack of association of these SNPs in a Japanese cohort is not due to ethnicity.


    This is the earlier Japanese study that failed to replicate Axial's findings.
    A replication study for association of 53 single nucleotide polymorphisms in a scoliosis prognostic test with progression of adolescent idiopathic scoliosis in Japanese.
    Spine (Phila Pa 1976). 2013 Jul 15

    METHODS: We recruited 2117 patients with AIS with 10 or more (Cobb angle) of scoliosis curves. They were divided into progression and nonprogression groups according to their Cobb angle. We defined the progression of the curve as Cobb angle more than 50 for skeletally mature subjects and more than 40 for immature patients, subjects. We defined the nonprogression of the curve as Cobb angle 50 or less only for skeletally mature subjects. Of the 2117 patients, 1714 patients with AIS were allocated to either the progression or nonprogression group. We evaluated the association of 53 SNPs with curve progression by comparing risk allele frequencies between the 2 groups.

    RESULTS: We evaluated the progression (N = 600) and nonprogression (N = 1114) subjects. Their risk allele frequencies were not different significantly. We found no replication of the association on AIS curve progression in any of the SNPs.
    Last edited by Dingo; 04-05-2015 at 02:18 AM.

  2. #2
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    According to this page on PubMed the list price for a ScoliScore test is $2,950.

    I checked the main ScoliScore website here and it appears that Transgenomic is still selling them.

    For what it's worth this is what their marketing department wrote on the front page.
    The ScoliScore AIS Prognostic Test is the first clinically validated and highly accurate prognostic test for Adolescent Idiopathic Scoliosis (AIS) curve progression

    This was at the bottom of the ScoliScore landing page and I found it a bit interesting.
    Copyright 1997-2012 Transgenomic, Inc., All Rights Reserved.

    The company hasn't updated the copyright info in 3 years. Yikes! However in fairness to the executives at Transgenomic their inverted stock chart suggests they have bigger problems to worry about than expired copyright information.
    Last edited by Dingo; 04-05-2015 at 01:33 PM.

  3. #3
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    Here is a link to the original study published in 2010 that "validated" the Scoliscore test. The first two authors are Axial Biotech employees. I didn't check to see who employed the other people.

    Dr. James Ogilvie: Founder and Chief Medical Officer at Axial Biotech
    Dr. Kenneth Ward: Chief Scientific Officer at Axial Biotech

    Validation of DNA-based prognostic testing to predict spinal curve progression in adolescent idiopathic scoliosis.
    Ward K, Ogilvie JW, Singleton MV, Chettier R, Engler G, Nelson LM.
    Spine (Phila Pa 1976). 2010 Dec 1

    STUDY DESIGN: Validation of a prognostic DNA marker panel.

    OBJECTIVE: The goals of this study were to develop and test the negative predictive value of a prognostic DNA test for adolescent idiopathic scoliosis (AIS) and to establish clinically meaningful endpoints for the test.

    SUMMARY OF BACKGROUND DATA: Clinical features do not adequately predict which children diagnosed with minimal or mild AIS will have the progressive form of the disease; genetic markers associated with curve progression might offer clinically useful prognostic insights.

    METHODS: Logistic regression was used to develop an algorithm to predict spinal curve progression incorporating genotypes for 53 single nucleotide polymorphisms and the patient's presenting spinal curve (Cobb angle). Three cohorts with known AIS outcomes were selected to reflect intended-use populations with various rates of AIS progression: 277 low-risk females representing a screening cohort, 257 females representing higher risk patients followed at referral centers, and 163 high risk males. DNA was extracted from saliva, and genotypes were determined using TaqMan assays. AIS Prognostic Test scores ranging from 1 to 200 were calculated.

    RESULTS: Low-risk scores (<41) had negative predictive values of 100%, 99%, and 97%, respectively, in the tested populations. In the risk model, we used cutoff scores of 50 and 180 to identify 75% of patients as low-risk (<1% risk of progressing to a surgical curve), 24% as intermediate-risk, and 1% as high-risk.

    CONCLUSION: Prognostic testing for AIS has the potential to reduce psychological trauma, serial exposure to diagnostic radiation, unnecessary treatments, and direct and indirect costs-of-care related to scoliosis monitoring in low-risk patients. Further improvements in test performance are expected as the optimal markers for each locus are identified and the underlying biologic pathways are better understood. The validity of the test applies only to white AIS patients; versions of the test optimized for AIS patients of other races have yet to be developed.
    Last edited by Dingo; 04-05-2015 at 05:19 PM.

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    Scoliscore's repeated failure follows a familiar pattern seen in earlier research on Scoliosis and other common diseases. At first common, widespread diseases have a tendency to look genetic because that's the direction that research dollars flow. But as time rolls on research progresses and expands and the importance of genes and heredity tends to fade into the background as environment moves to the front. Keep that in mind the next time you read a headline that scientists "think" they've found the gene for a common problem like depression, heart disease or cancer. If you read the fine print many times what they've found is a weak association and in a majority of cases these genes will be quietly "unfound" in future studies.

    In 1998 a small Japanese study found that the concordance rate for AIS in identical twins approached 100%. This was used by many people to argue that Scoliosis was a genetic disease.

    Idiopathic scoliosis in twins studied by DNA fingerprinting: the incidence and type of scoliosis.
    J Bone Joint Surg Br. 1998 Mar
    Abstract: We investigated 21 pairs of twins for zygosity and idiopathic scoliosis. DNA fingerprinting confirmed that 13 pairs were monozygotic and eight were dizygotic. There was concordance for idiopathic scoliosis in 92.3% of monozygotic and 62.5% of dizygotic twins. Of the 12 pairs of monozygotic twins concordant for idiopathic scoliosis, six showed discordant curve patterns but eight had differences in Cobb angle of less than 10 degrees. Seven of the ten pairs of monozygotic twins had similar back shapes. Our findings suggest that there is a genetic factor in the aetiology of idiopathic scoliosis; they also indicate that there is a genetic factor in both the severity of the curve and the general shape of the back.

    When larger studies were conducted they produced a very different answer.

    Adolescent idiopathic scoliosis in twins: a population-based survey.
    Spine (Phila Pa 1976). 2007 Apr 15
    STUDY DESIGN: A questionnaire-based identification of adolescent idiopathic scoliosis (AIS) patients in a twin cohort.
    OBJECTIVE:The purpose of this study was to establish a scoliosis twin cohort to provide data on the heritability of AIS.
    SUMMARY OF BACKGROUND DATA: The etiology of AIS is still unclear, and the true mode of inheritance has yet to be established. Concordance rates in monozygotic twins have been reported to be between 0.73 and 0.92, and in dizygotic twins between 0.36 and 0.63. Studies on concordance in twin pairs provide a basis for analyzing the influence of genetic versus environmental factors.
    METHODS:All 46,418 twins registered in the Danish Twin Registry born from 1931 to 1982 were sent a questionnaire, which included questions about scoliosis. A total of 34,944 (75.3%) representing 23,204 pairs returned the questionnaire.
    RESULTS: A subgroup of 220 subjects considered to have AIS was identified, thus giving a prevalence of 1.05%. The concordant twin pairs were all monozygotic. Pairwise, the concordance rate was 0.13 for monozygotic and zero for dizygotic twin pairs; proband-wise concordance was 0.25 for monozygotic and zero for dizygotic pairs. The concordance of monozygotic and dizygotic pairs was significantly different (P < 0.05).
    CONCLUSION: We have found evidence for a genetic etiology in AIS, but the risk of developing scoliosis in 1 twin whose other twin has scoliosis is smaller than believed up until now.

    In the most recent large, twin study scientists concluded that the environment was the most important factor for Scoliosis. Heredity continued it's predictable fade into the background.

    Heritability of scoliosis.
    Eur Spine J. 2012 Jun
    PURPOSE: To estimate the heritability of scoliosis in the Swedish Twin Registry.
    METHODS: Self-reported data on scoliosis from 64,578 twins in the Swedish Twin Registry were analysed. Prevalence, pair- and probandwise concordances and tetrachoric correlations in mono- and dizygotic same-sex twins were calculated. The relative importance of genetic variance, i.e. the heritability, and unique and shared environmental variance was estimated using structural equation modelling in Mx software. In addition, all twins in the twin registry were matched against the Swedish Inpatient Register on the primary diagnosis idiopathic scoliosis.
    RESULTS: The prevalence of scoliosis was 4%. Pair- and probandwise concordance was 0.11/0.17 for mono- and 0.04/0.08 for same-sex dizygotic twins. The tetrachoric correlation (95% CI) was 0.41 (0.33-0.49) in mono- and 0.18 (0.09-0.29) in dizygotic twins. The most favourable model in the Mx analyses estimated the additive genetic effects (95% CI) to 0.38 (0.18-0.46) and the unique environmental effects to 0.62 (0.54-0.70). Shared environmental effects were not significant. The pairwise/probandwise concordance for idiopathic scoliosis in the Swedish Inpatient Register was 0.08/0.15 for monozygotic and zero/zero for same-sex dizygotic twins.
    CONCLUSION: Using self-reported data on scoliosis from the Swedish Twin Registry, we estimate that 38% of the variance in the liability to develop scoliosis is due to additive genetic effects and 62% to unique environmental effects. This is the first study of sufficient size to make heritability estimates of scoliosis.
    Last edited by Dingo; 04-05-2015 at 11:28 PM.

  5. #5
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    In a manner not so different from what happened with ScoliScore here is an example of a Scoliosis gene that was quietly, "unfound."

    Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population.

    However in ScoliScore's case it wasn't 1 gene that was "unfound". All 53 genes were unfound. I'm sure that raises some eyebrows in the scientific community.

    Perhaps the two men behind the ScoliScore test will address why all 53 genetic associations in their $2950 test were false positives.
    Dr. James Ogilvie: Founder and Chief Medical Officer at Axial Biotech
    Dr. Kenneth Ward: Chief Scientific Officer at Axial Biotech
    Last edited by Dingo; 04-05-2015 at 11:29 PM.

  6. #6
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    You see Pooka, You can't even trust the scientists either.

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