Wow; what else that we think we know about MS is wrong? #MSBlog #MSResearch
“The great tragedy of science – the slaying of a beautiful hypothesis by an ugly fact.” Thomas Huxley
“The higher transmission rate of MS down the maternal (mother), compared to the paternal (father), line has been used as an argument to support many theories about the cause of MS. For example, the vertical transmission (mother-to-child) of an infectious agent or epigenetics* due to an intrauterine environmental effect. The large Swedish registry study below refutes this finding and suggests there is no increased maternal transmission of the disease. Who do you believe? The Swedish study is a population level study and is less likely to affected by recall bias.”
*Epigenetics are changes to the control of the genome or DNA, independent of the genetic code, that affect how the genome is controlled. Epigenetics is one way how the environment interacts with our genes.
“This study therefore casts doubt on the intrauterine effect, and hence the epigenetic model of MS causation. I am in shock. I will need to step back and reconsider my position on a lot of things. This study also suggests that the familial risk has been overplayed in the past. Again this challenges current dogma that is probably based on flawed ascertainment in other studies, i.e. people with a positive family history of MS are more likely to be diagnosed with MS and volunteer for studies. I can imagine somebody with a family member who has MS being more likely to have symptoms investigated, and hence being diagnosed with MS, and volunteering for research.”
“I think we need to get Professor Jan Hillert and Professor George Ebers to debate this paper and the implications of its findings on their thinking. Believe me the issues this paper raises are not trivial.”
“I must congratulate the Swedes on a wonderful paper. Well done.”
Epub: Westerlind H, Ramanujam R, Uvehag D, Kuja-Halkola R, Boman M, Bottai M, Lichtenstein P, Hillert J. Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden. Brain. 2014 Jan.
Background: Data on familial recurrence rates of complex diseases such as MS give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias.
Methods: Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 MSers were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of MSer.
Results: Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42-7.86). Surprisingly, despite a well-established lower prevalence of MS among males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called ‘Carter effect’ could not be excluded. We estimated the heritability of MS using 74 757 twin pairs with known zygosity, of which 315 were affected with MS, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36-0.76), whereas the shared environmental component was estimated to be 0.01 (0.00-0.18).
Conclusion: In summary, whereas MS is to a great extent an inherited trait, the familial relative risks may be lower than usually reported.