Effect of Early Life Events on Latitude Gradient for Multiple Sclerosis

Post by Lincoln Tracy

What's the science?

The prevalence, incidence, and mortality of multiple sclerosis (MS) has been reported to have distinct geographical and temporal patterns. Specifically, increasing latitude towards the poles is associated with increased prevalence. Scientists have considered latitude as a surrogate for environmental factors, such as UV exposure, given previous studies report a link between lower UV exposure and an increased risk of MS. An important limitation of previous studies has been the neglect of an individual’s long-term migration history, resulting in a failure to acknowledge the exposures accumulated over a lifetime. This week in Brain, Sabel and colleagues examined if and when lifetime population migration impacts the previously reported MS latitudinal gradient in New Zealand. They used data from a national MS prevalence study, conducted in tandem with the national population census.  

How did they do it?

The authors used data from the New Zealand national MS prevalence study, conducted on March 7, 2006. Specifically, they focused on a cohort of 1587 individuals with MS who were born in New Zealand and could provide a complete residential history from their conception to diagnosis. The geography of New Zealand was stratified into six broad latitudinal regions from the north to the south. First, they examined how lifetime population migration affects the latitude gradient for MS prevalence. To do this, they compared prevalence gradients between where people with MS were born, and where they were living in 2006. Second, they examined whether sex and disease course phenotype affected the latitude gradient. Third, they considered the effects of age and looked at what part of an individual’s life the effect of latitude on MS risk begins. Fourth, they then examined how different types of migration (i.e., diagnosed in 2006 at their 2006 location, born in a region other than where they lived in 2006 and then moved there, etc.) affected the MS risk gradients.   

What did they find?

First, the authors found a higher, but not statistically significant, gradient between the location of birth and MS prevalence when compared to a residential location in 2006. The stronger signal from the birthplace location is consistent with the latitudinal gradient becoming established prior to migration occurring. Second, they found the latitude gradient was driven by females with relapsing onset MS, rather than females with progressive MS or men with either kind of MS. Third, they found that the south to north latitude gradient was present at the time of birth. The gradient remained relatively stable until the age of 12 but then declined as individuals began to migrate. Fourth, they found that the gradient was being driven by individuals who either moved away from and then returned to their birth residence by 2006 or had never resided anywhere other than where they lived in 2006. This effect was particularly prominent for individuals in the southernmost region of New Zealand.

What's the impact?

This study demonstrates the gradient (and risk exposure) for MS is established early in life, potentially during gestation. The act of migration itself does not appear to influence the MS gradient in New Zealand. Rather, the effects of migration are more visible in subsequent years, where it dilutes the relationship between birthplace and latitude. These findings suggest that modifiable environmental factors to reduce the risk of MS (e.g., sunlight exposure, vitamin D deficiency), need to be addressed at the earliest possible stages of pregnancy and the neonatal period.  

Sabel et al. The latitude gradient for multiple sclerosis prevalence is established in the early lifecourse. Brain (2021). Access the original scientific publication here.