People with a certain type of genetic makeup who’ve have head trauma may have a risk of developing multiple sclerosis (MS) up to nearly 18 times over those without genetic factors or a history of head trauma, a study shows.

“Our study could prompt further research to uncover the underlying mechanisms linking head trauma, genetic factors and MS development,” wrote the researchers, who said for policymakers and doctors, it “may also contribute to policy discussions regarding preventive measures and risk assessment strategies.”

The study, “Head trauma results in manyfold increased risk of multiple sclerosis in genetically susceptible individuals,” was published in the Journal of Neurology, Neurosurgery, and Psychiatry.

In MS, the immune system mistakenly attacks the brain and spinal cord, triggering inflammation. What exactly causes MS isn’t known, but a number of genetic and environmental factors are thought to play a role.

Mounting evidence shows that head trauma — any damage to the scalp, skull, or brain resulting from injury, for example, a violent blow or jolt to the head or body — may put people at increased risk of developing the disease later in life.

“Recent large register-based studies have reported an increased risk of MS following traumatic brain injury, particularly if repeated and requiring longer hospital care,” the researchers wrote, noting that head trauma may cause the brain to become inflamed.

They suggest a person’s genetic makeup may further increase the risk of MS following head trauma. There’s “a complex interplay between environmental and genetic risk factors,” wrote the researchers, who focused on the human leukocyte antigen (HLA) family of genes, which help the immune system discern foreign material from healthy tissues. The DRB1*15:01 allele is linked to a higher risk of developing MS, whereas the HLA-A*02:01 allele appears to protect against MS. An allele is a variant form of a gene that arises through mutation or genetic recombination.

To collect data about demographic factors, environmental exposures, and lifestyle habits from April 2005 to April 2015, the researchers sent out a questionnaire to people in Sweden, ages 16-70, with or without a diagnosis of MS.

Increased risk with genetic factors, head trauma

The questionnaire asked people if they’d ever hit their head badly, if it made them lose consciousness or memory, and how many times it had happened in the previous five years. A total of 2,807 people with MS and 5,950 people without MS (controls) responded. The mean age at disease onset was 34.6 and the median duration from disease onset to diagnosis was a year.

Head trauma was reported by 888 (31.6%) people with MS and 1,559 (26.2%) controls. Having head trauma increased the risk of developing MS by 30%. For those who reported head trauma in the previous five years, the risk was 60% higher compared with not having head trauma.

Having loss of consciousness or memory loss with head trauma didn’t significantly raise the risk of MS. However, there was a significant trend “showing increased risk of MS with increasing number of head impacts,” the researchers wrote. “We observed an increased risk of developing MS following head trauma, particularly if the head trauma occurred within a [five]-year time frame before disease onset.”

Blood samples were available from 2,057 people with MS and 2,887 controls. Genetic testing revealed 1,122 (54.5%) people with MS and 801 (27.7%) controls carried the DRB1*15:01 allele. The proportion of those without the protective HLA-A*02:01 allele was 58.6% and 45.9%, respectively.

Compared with people without these two genetic factors who’d never had head trauma, the risk of developing MS was increased by 18 times among those with both genetic factors who had experienced head trauma within five years before the onset of disease. A weaker connection between genetic risk factors and a history of head trauma that occurred more than five years before disease onset was also observed.

Carrying either of the two genetic factors also increased the risk of MS in people with a history of head trauma. “Our findings indicate that individuals carrying the main MS-associated HLA risk allele DRB1*15:01 or lacking the protective allele HLA-A*02:01 are more susceptible to the effects of head trauma,” the researchers wrote.

Those younger than 20 at disease onset who’d had head trauma had a 1.39 times higher odds of developing MS. This number was similar (1.31 times) among those who were older. The interaction between head trauma and HLA-DRB1*15:01 was significant in both age groups.

“We also observed synergistic effects [a joint effect beyond the sum of the independent effects] between head trauma and MS-associated HLA risk alleles in relation to MS risk,” said the researchers, who noted more research “to elucidate the underlying mechanisms and explore preventive strategies” is needed.