title: Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Simpson
authors.forename: Leigh
authors.initials: L
authors.lastname: Blizzard
authors.forename: Petr
authors.initials: P
authors.lastname: Otahal
authors.forename: Ingrid
authors.initials: I
authors.lastname: Van der Mei
authors.forename: Bruce
authors.initials: B
authors.lastname: Taylor
mesh_terms: D000483:Alleles; D044362:Australasia; D003431:Cross-Cultural Comparison; D003430:Cross-Sectional Studies; D005060:Europe; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D015994:Incidence; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D009656:North America; D012307:Risk Factors; D019371:Topography, Medical; D014466:Ultraviolet Rays
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains