Part 1 · The disease
Genes & risk factors
What raises the risk of MS, and by how much: HLA genes, Epstein-Barr virus, vitamin D, smoking and teenage obesity on one odds-ratio scale, with family risk shown as real percentages.
Log scale: equal steps mean equal multiples of risk. Whiskers are 95% confidence intervals; a paler bar with a dashed outline marks early evidence. Measures differ (odds ratio, relative risk, hazard ratio) and come from different populations, so compare each bar with 1, not bars with each other.
Family risk: relative versus absolute
"Seven times the risk" sounds alarming. Switch to absolute risk to see what it means for a sibling or a child, using the age-adjusted Swedish registry figures.
Relative risks and age-adjusted absolute risks from the Swedish population registry; general-population lifetime risk and twin concordance from Danish and Canadian studies. Different studies, so the numbers are not exactly comparable.
There is no genetic test for MS. No genetic test is used to diagnose MS or to predict who will develop it; genetic testing for MS is used only in research, and a person can carry many risk variants and never develop MS. 331 Polygenic scores separate groups (AUC 0.73–0.80) 429, but a prediction review judged them "unlikely to ever" be clinically helpful for an individual, though useful for choosing people for prevention trials. 211
Genes and environment multiply
Risk factors do not simply add. Pick a combination, or play the chart to see what happens when smoking meets the two HLA risk factors (carrying DRB1*15 and lacking A*02).
Each odds ratio compares the group with people who have neither factor, in Swedish case-control studies.
EBV comes first: the military cohort
Bjornevik and colleagues followed more than 10 million young adults on US military duty, using blood samples stored over years. Step through one person's timeline.
The neurofilament curves are schematic; only their order is from the study (level before and at seroconversion, rising after it in future cases). Onset is drawn at the reported median of 7.5 years.
Vitamin D: a live controversy
Low vitamin D is linked to MS risk in several kinds of study. Trials of high-dose vitamin D in people who already have MS or a first episode give a more mixed picture. Compare the two bodies of evidence.
Dots are estimates, lines 95% confidence intervals. A line crossing 1 is compatible with no effect. Units differ between rows.
Can MS be prevented?
No intervention has been proven to prevent MS in the general population. The only randomised evidence of delaying a first clinical event comes from people with radiologically isolated syndrome (RIS): MS-like lesions found by chance on MRI, with no symptoms. 277,367