- Genetic changes influence about 30% of the overall MS risk, with lifestyle and environmental factors accounting for the rest.
- The geographical and ethnic distribution of MS prevalence varies greatly, and in Europe, the prevalence is much higher in the north. The origins and reasons for this variation are still poorly understood.
- Researchers have examined ancient DNA spanning various eras to unravel the origins of MS risk genes in Europe.
Genetics and MS
There are currently over 200 genetic changes linked to MS onset, with most of these found in the human leukocyte antigen (HLA) region. HLAs are proteins found on the surface of almost all cells in the body. This region is important in helping our immune system distinguish between our own cells and harmful invaders like viruses or bacteria.
Genetic factors are believed to account for approximately 30% of the total risk associated with MS, with the remaining contribution from environmental and lifestyle factors, such as smoking, obesity, and Epstein-Barr virus (EBV) infection.
The prevalence of MS exhibits geographical and ethnic variability. In Europe, the prevalence of MS is significantly higher in the north. The origins and reasons for this variation are still poorly understood. However, these differences may provide clues as to why MS has continued to rise.
It is suggested that differences in the global prevalence of MS may be partly explained by the genetic background of different populations. For example, among African American individuals with MS, there is a higher proportion of genetic traits associated with European ancestry compared to those without MS.
This European genetic influence appears to increase the risk of MS. On the other hand, Asian American individuals with MS have less of this European genetic influence.
What is the reason for these variations, and where do they come from?
What did the researchers do?
Published in the prestigious journal, Nature, the researchers used a large ancient genome dataset (from the Mesolithic period to the Bronze Age), as well as new medieval and post-medieval genome datasets to determine present-day European ancestry relative to these ancestral populations to identify signs of lifestyle-specific evolution.
They determined whether genetic changes associated with an increased risk in MS have undergone positive selection, when this selection occurred and whether the targets of selection were specific to lifestyle.
Finally, the team examined the environmental conditions that may have caused the selection of MS risk genes, including survival strategies and exposure to pathogens.
Where did MS genetic risk originate from?
The researchers found that many of the genetic changes associated with increased MS risk first appeared in a herding population (who lived a semi-nomadic life and bred livestock), called the Yamnaya people, who emerged from a region spanning north-east Bulgaria, south-east Romania, Moldova, Ukraine, Russia, and north-west Kazakhstan.
The Yamnaya people migrated to Europe about 5,000 years ago, most likely bringing along this genetic risk, which has since spread across the northern regions of the continent.
What genetic changes were most frequent?
Genetic changes in the HLA region were prominent in ancient groups. A genetic change known as HLA-DRB1*15:01, which carries the highest risk for MS, was first detected in an Italian Neolithic individual (approximately 5,800 BC) and increased in frequency around the emergence of the Yamnaya culture.
Using the UK Biobank, a large-scale biomedical database, the researchers found that the frequency of HLA-DRB1*15:01 was highest in modern populations from Finland, Sweden, Iceland and in ancient populations with herding ancestry.
Why are these genetic changes still around if they confer MS risk?
This is a good question. It is likely these genetic changes provided some survival advantage, despite their current association with MS risk.
Indeed, many of the genetic changes that underwent positive selection were linked to providing protection against pathogens or infectious diseases.
What is the significance of this research?
The late Neolithic period and Bronze Age were critical times in human history during which highly genetically and culturally divergent populations evolved and mixed.
Additionally, the emergence of the herding lifestyle, which is often overlooked in comparison to the shift to farming in the Neolithic era, may have had an equal or even greater impact on our immune responses.
This research improves our understanding of how the lifestyle and environment of our ancestors impacted our immune responses and its subsequent effect on the risk of developing MS.