The risk of developing multiple sclerosis (MS) was similar between first- and second-degree family members of people with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS). The findings, which were consistent with previous studies suggesting that genetics and environment are relatively equal contributors to disease risk, also indicate that the likelihood of developing a particular MS type may be independent of genetics. The study, "The familial risk and heritability of multiple sclerosis and its onset phenotypes: A case–control study," was published in the Multiple Sclerosis Journal. RRMS makes up about 85% of all newly diagnosed MS cases. RRMS is the most common form of the neurodegenerative disease, accounting for about 85% of all newly diagnosed cases. It's characterized by periods of inflammatory disease activity, or relapses, interspersed with periods of remission. A PPMS diagnosis is more rare, diagnosed in about 15% of MS patients. It is typically linked to a more aggressive disease course and worse responses to disease-modifying treatments. While these patients exhibit less active brain inflammation, they tend to have more brain lesions and atrophy, or tissue wasting. Given the differences in disease expression between these two MS types, it's possible that different risk factors, including genetic ones, are involved in their development, but such factors are not well-understood. MS is not specifically considered a heritable disease, meaning a person's parent does not directly pass down a genetic mutation that means they will get MS. Still, a person's genetic makeup can profoundly influence MS risk and disease expression. About 20% of MS patients have a family history of MS. However, it is not known whether genetic contributions to MS risk differ between the RRMS and PPMS subtypes. In the recent study, researchers in Sweden aimed to explore this question by looking at data from all people diagnosed with MS in Sweden between 1987 and 2019 with available records in national health databases. This included 25,186 MS cases: 1,593 with PPMS and 16,718 with RRMS at diagnosis, while the remaining 6,875 people had an unknown MS type. For each MS case, 10 sex- and age-matched healthy people were also included, totaling 251,881 healthy control samples. Results showed that the odds of an MS diagnosis were increased by about sevenfold in first-degree relatives of the RRMS patients. Likewise, the odds were increased by eightfold in first-degree relatives of the PPMS patients. The odds were lower, but still increased, in second-degree relatives. Specifically, such family members of RRMS patients were at a 2.16 times higher risk of MS and second-degree family of PPMS patients were at a 2.18 times higher risk. As observed in previous studies, the familial risk of MS was highest among full siblings for both MS types. Overall, the genetic contributions to MS development were not found to be significantly different between the two MS types. About half of MS risk is estimated to be genetic. Based on the findings, the heritability, or the proportion of disease risk explained by genetic factors, was estimated to be about 51% for MS overall, which was similar to the heritability specifically of RRMS (55%). Essentially, that means that about half of MS risk is estimated to be genetic, whereas the rest would be assumed to be environmental. Estimated genetic contributions to PPMS were 23%, but this lower value is likely related to the smaller number of patients and lower statistical power, the researchers noted. Scientists also estimated that the heritability of MS onset age was about 21.9%. The comparable risk of MS between different disease types suggests "shared aetiology between them," the researchers wrote, noting that the demographic and clinical differences between them could be "explained by other factors than genetics." Future research should examine "more complex severity traits" instead of only MS type to better understand how "unexplored genetic or environmental risk factors" contribute to disease expression, according to the scientists. The researchers also noted that more precise genetic sequencing approaches combined with larger family-based studies will enable more accurate estimates of MS heritability in the future.