| Title: | 026 Gene-environment interactions in multiple sclerosis: a UK Biobank study |
| Journal: | Journal of Neurology Neurosurgery & Psychiatry |
| Published: | 27 May 2022 |
| DOI: | https://doi.org/10.1136/jnnp-2022-abn.65 |
| URL: | https://doi.org/10.1101/2020.03.01.971739 |
Publication 8403
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Abstract
Question: Does genetic risk modify the effect of environmental MS risk factors? Methods Case-control study of 2151 people with MS and 486,125 controls using data from a longitudinal cohort (UK Biobank). MS was defined using ICD-coding or self-report. Associations with MS risk were quan- tified using multivariate logistic regression. Interaction between environmental and genetic risk factors was quantified using the Attributable Proportion due to interaction (AP). Model fits were quantified using Nagelkerke's pseudo-R2 metric. Results Exposures associated with MS were childhood obesity (OR=1.39, 95%CI 1.22-1.58), smoking (OR=1.19, 95%CI 1.07-1.33), and earlier menarche 0.95, 95%CI 0.92-0.98). The autosomal polygenic risk score (PRS) was associated with MS disease status (ORTop-vs-bottom-decile=3.93, 95%CI 3.11-4.97). There was evidence of synergistic interaction between the PRS and both childhood obesity (AP=0.111, 95%CI 0.007-0.202), and smoking (AP=0.106, 95%CI 2.24e-4 to 0.196). Conclusions We provide novel evidence for interaction between environmental risk factors for MS and a high burden of autosomal genetic risk. These findings have significant implications for our understanding of MS biology, and may inform targeted prevention strategies. ben.meir.jacobs@gmail.com </p>
6 Authors
- Benjamin Jacobs
- Alastair Noyce
- Jonathan Bestwick
- Daniel Belete
- Gavin Giovannoni
- Ruth Dobson
Enabling scientific discoveries that improve human health