Utilising population-based collections from the UK to identify genetic risk factors for idiopathic scoliosis

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Dr Emma Clark, Dr Nic Timpson, Dr Frances Williams, Twins-UK

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Adolescent Idiopathic Scoliosis (AIS) accounts for the majority of cases of idiopathic scoliosis, and has a prevalence of approximately 3%. Current knowledge on the causes of initiation or progression of scoliotic curves is scarce. There is considerable interest in exploring the genetic basis of scoliosis, as a means of improving understanding of its pathogenesis and natural history. Twin studies consistently show monozygotic twins have a higher concordance rate for scoliosis than dizygotic twins (73% versus 36%), suggesting an underlying genetic component is important, although the architecture of this effect is unknown. Genome wide studies (GWAS) have been used in a Japanese case-control study and it identified the SNP rs11190870 to be associated with scoliosis risk. This variant has now been replicated in an independent southern Chinese population, but a systematic search for genetic variation associated with scoliosis in European populations has not been performed.

Aims & objectives

We wish to build our current scoliosis research using ALSPAC by utilising genetic data already collected. In addition, we also wish to extend into another collection, Twins-UK, that has contact with over 12,000 twins, and has collected a wide range of clinical, biological and genetics data similar to ALSPAC. This similarity will allow us to combine data from Twins-UK and ALSPAC, and will increase power to identify rarer genetic determinants, or those with smaller effect sizes.


1. Obtain measures of scoliosis from participants in Twins-UK aged ≤45. The PhD student will apply the DXA Scoliosis Method (DSM) to eligible DXA scans in Twins-UK.
2. Investigate if the SNP rs11190870 is associated with the presence of scoliosis in ALSPAC and Twins-UK. Pilot data shows the allele frequency is similar in ALSPAC to the Asian populations
3. Perform GWAS followed by meta-analysis in ALSPAC and Twins-UK. If SNPs are identified as associated with scoliosis risk with sufficient evidence in ALSPAC alone (P<5x10-8 in tests of association) these data will be replicated using data from Twins-UK. However, in the absence of association identified using ALSPAC alone, a meta-analysis will be performed of the ALSPAC and Twins-UK GWAS data.
4. Evaluate if identified novel SNPs are likely to have biological relevance bioinformatically and by utilising gene expression, DNA methylation and metabolomic data collected across ALSPAC and Twins-UK


Taylor HJ et al Identifying scoliosis in population-based cohorts: Development and validation of a novel method based on total body DXA scans. Calc Tis Int 2013;92:539
Takahashi Y et al A genome-wide association study identifies common variants near LBX1 associated with AIS. Nat Gen 2011;43:1237

Created on Oct. 1, 2015, 9 a.m.

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