In the following study on the ‘MS endophenotype‘ we set out to study the feasibility of developing a MS risk score in the hope that we can identify a cohort of people from the general population at very high risk of developing MS. In summary, the algorithm, or risk score, we tested works. We were able to create a hierarchy of risk based on genetics (HLA-DRB1*1501), demographics (gender, month of birth) and environmental factors (smoking, history of IM, EBV serology, vD). In our model vD was not predictive simply because too many pwMS were on vD supplements.
Dobson et al. A Risk Score for Predicting Multiple Sclerosis. PLoS One. 2016 Nov 1;11(11):e0164992.
OBJECTIVE: Multiple sclerosis (MS) develops as a result of environmental influences on the genetically susceptible. Siblings of people with MS have an increased risk of both MS and demonstrating asymptomatic changes in keeping with MS. We set out to develop an MS risk score integrating both genetic and environmental risk factors. We used this score to identify siblings at extremes of MS risk and attempted to validate the score using brain MRI.
METHODS: 78 probands with MS, 121 of their unaffected siblings and 103 healthy controls were studied. Personal history was taken, and serological and genetic analysis using the illumina immunochip was performed. Odds ratios for MS associated with each risk factor were derived from existing literature, and the log values of the odds ratios from each of the risk factors were combined in an additive model to provide an overall score. Scores were initially calculated using log odds ratio from the HLA-DRB1*1501 allele only, secondly using data from all MS-associated SNPs identified in the 2011 GWAS. Subjects with extreme risk scores underwent validation studies. MRI was performed on selected individuals.
RESULTS: There was a significant difference in the both risk scores between people with MS, their unaffected siblings and healthy controls (p<0.0005). Unaffected siblings had a risk score intermediate to people with MS and controls (p<0.0005). The best performing risk score generated an AUC of 0.82 (95%CI 0.75-0.88).
INTERPRETATIONS: The risk score demonstrates an AUC on the threshold for clinical utility. Our score enables the identification of a high-risk sibling group to inform pre-symptomatic longitudinal studies.
Feb 18, 2011 … Towards an endophenotype in multiple sclerosis. This study is recruiting people with MS who have brothers and/or sisters without MS, and …