Multiple sclerosis (MS) prevalence is geographically heterogeneous, with higher rates among populations of European ancestry and higher latitudes1. The geographical distribution of MS risk raises the hypothesis that local adaptation, potentially driven by solar radiation, has contributed to shaping the genetic susceptibility landscape of MS. Therefore, we aim to investigate whether genetic variants associated with MS show local adaptation signals in response to solar radiation and daytime temperature levels in the UK population. This allows us to determine how solar radiation exposure may have influenced the evolution of MS genetic risk.
We applied a landscape genomics approach using genotype and geographical data of 20,000 individuals in the UK Biobank2, coupled with solar radiation data from the WorldClim dataset. We conducted genome-wide logistic regression models to identify genetic regions associated with MS and exhibiting selection signals influenced by solar radiation levels, to detect MS associated genomic regions that show signals of selection influenced by solar radiation exposure.
A genome-wide significant signals of local adaptation in response to solar radiation levels was detected at rs5743618 on chromosome 4, a missense single nucleotide polymorphism in TLR1 that has previously been shown to be under selection in European populations3. The gene TLR1 is in a biological pathway with genes NFkB and CYP27B1, both identified to increase MS risk by the International Multiple Sclerosis Genetics Consortium4.
These findings suggest that solar radiation may have shaped the genetic architecture underlying MS susceptibility in the UK. Ongoing analysis focuses on refining these findings, by examining haplotype structure and genetic covariance to further understand environmental influences on multiple sclerosis risk variants.