Dive into prehistory to try to better understand multiple sclerosis

Multiple sclerosis is an autoimmune disease that is more common in northern Europeans, and whose prevalence has increased over the past fifty years. This increase in cases suggests that its triggering is due to a poorly understood combination of environmental and genetic factors.

A series of studies published in journals Nature suggests that the migration of pastoralist populations that occurred five thousand years ago may have contributed to the increased genetic risk of multiple sclerosis in northern Europe. This additional risk may have been offset by protection against diseases transmitted by animals (zoonosis).

Aske Willerslev (University of Cambridge and Copenhagen) and colleagues relied on more than 1,600 prehistoric human genomes covering 34,000 years of European populations. These data refine the history of migrating waves: after the arrival from Africa, 45,000 years ago, of the first hunter-gatherers. Homo sapiens, Neolithic farmers from the Near East in turn ventured into Western Europe eleven thousand years ago. Then, about five thousand years ago, the nomadic shepherds of the steppe from the Danube to the Urals made their way into the sunset.

Inflammatory Diseases in the Bronze Age

Later, representatives of the so-called “Yamana” culture, may have mutated their genetic material in favor of the occurrence of multiple sclerosis. The researchers relied on “genome-wide association studies” (GWAS), which compare numerous modern genomes to establish relationships between physical and/or behavioral traits and genetic mutations. No fewer than 233 genetic variants have been identified in association with multiple sclerosis, particularly the HLA-DRB1*15:01 variant, of which carriers are three times more likely to develop the disease.

Today, the highest proportions of carriers of this mutation are found in Finland, Sweden and Iceland. Among ancient populations, the Yamanayas present more of this genetic profile. Plains genetic inheritance, more present in the north, would therefore partially explain the gradient in the prevalence of multiple sclerosis in southern Europe, with more than half affected.

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Luis Quintana-Murci, a population geneticist at the Pasteur Institute, judges these results. “very interesting”. Especially since they agree with his work, recently published cellOn the appearance of genetic profiles associated with inflammatory diseases in the Bronze Age, about 4,500 years ago. “These mutations together protect against more serious diseases, possibly infectious diseases – a phenomenon called ‘antagonistic pleiotropy'”

, he says. Like sickle cell disease, which protects African populations from malaria.

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