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global meta-analysis paper_forJNNP_for open access_all.doc (5.67 MB)

Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis

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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 behaviouralecultural 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.

History

Publication title

Journal of Neurology, Neurosurgery and Psychiatry

Volume

82

Issue

10

Pagination

1132-1141

ISSN

0022-3050

Department/School

Menzies Institute for Medical Research

Publisher

B M J Publishing Group

Place of publication

British Med Assoc House, Tavistock Square, London, England, Wc1H 9Jr

Rights statement

Copyright 2011 British Medical Journal Publishing Group.

Repository Status

  • Open

Socio-economic Objectives

Preventive medicine

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