Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis
- Correspondence to Associate Professor Bruce Taylor, Menzies Research Institute Tasmania, University of Tasmania, Private Bag 23, Hobart TAS 7001, Australia;
Contributors The project was conceived and planned by SSJ. The data collection/literature review was done by SSJ. SSJ, LB, PO and BT were involved in the conception of analyses used. SSJ implemented statistical analyses, supervised by LB, and PO undertook segmented analyses. SSJ, BT, LB and IVdM were involved in the initial drafting of manuscript. SSJ had full access to all of the aggregate-level data included in this study and takes responsibility for the integrity and accuracy of the data analyses therein.
- Received 6 January 2011
- Revised 21 February 2011
- Accepted 23 February 2011
- Published Online First 8 April 2011
Background There is a striking latitudinal gradient in multiple sclerosis (MS) prevalence, but exceptions in Mediterranean Europe and northern Scandinavia, and some systematic reviews, have suggested that the gradient may be an artefact. The authors sought to evaluate the association between MS prevalence and latitude by meta-regression.
Methods and findings Studies were sourced from online databases, reference mining and author referral. Prevalence estimates were age-standardised to the 2009 European population. Analyses were carried out by means of random-effects meta-regression, weighted with the inverse of within-study variance. The authors included 650 prevalence estimates from 321 peer-reviewed studies; 239 were age-standardised, and 159 provided sex-specific data. The authors found a significant positive association (change in prevalence per degree-latitude) between age-standardised prevalence (1.04, p<0.001) and latitude that diminished at high latitudes. Adjustment for prevalence year strengthened the association with latitude (2.60, p<0.001). An inverse gradient in the Italian region reversed on adjustment for MS-associated HLA-DRB1 allele distributions. Adjustment for HLA-DRB1 allele frequencies did not appreciably alter the gradient in Europe. Adjustment for some potential sources of bias did not affect the observed associations.
Conclusion This, the most comprehensive review of MS prevalence to date, has confirmed a statistically significant positive association between MS prevalence and latitude globally. Exceptions to the gradient in the Italian region and northern Scandinavia are likely a result of genetic and behavioural–cultural variations. The persistence of a positive gradient in Europe after adjustment for HLA-DRB1 allele frequencies strongly supports a role for environmental factors which vary with latitude, the most prominent candidates being ultraviolet radiation (UVR)/vitamin D.
Funding SSJ is supported by a Menzies Postgraduate Research Scholarship. IVdM is supported by an NHMRC Training Fellowship.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.