Ethnic differences in the phenotype and outcome of Amyotrophic Lateral Sclerosis: A meta-analysis of population-based studies (P4.143)

Objective: To review the changing phenotype and outcome of Amyotrophic Lateral Sclerosis in different ethnic groups. Background: Race and ethnicity might modulate disease via genetic background. There are elements from mixed populations to postulate divergent ALS phenotypic features. Knowledge on how ethnicity modifies ALS phenotype may provide important insight into the risk factors and pathogenic mechanisms of the disease. Methods: We performed a systematic review, meta-analysis and meta-regression of the data concerning the differences in phenotype and outcome of ALS as regards ethnicity. We aimed to produce synthesized epidemiological indicators. Sub-continent was used as a proxy for ethnicity. We also relied on data from public genomic databases. Results: We reviewed 3058 records. 78 population-based studies were selected, covering 40 geographical areas in 10 sub-continents. Characteristics of about 12,700 ALS cases from population-based studies were considered. The results highlight the phenotypic heterogeneity of ALS at time of onset (age, sex ratio (SR), bulbar onset), time of diagnosis (age, definite ALS according to El Escorial criteria), in early follow-up (comorbidities), and late follow-up (survival since onset or diagnosis). A major explanatory variable of the variability of ALS phenotype in population-based studies is sub-continent. Some markers of ALS phenotype have homogeneous distribution in western countries (SR, mean age at onset/diagnosis) but their distribution in other subcontinents is remarkably different. Other markers present variations even in European subcontinents and in other continents (familial ALS, bulbar onset, definite ALS). As a consequence, ALS outcome varies significantly, with a median survival time since onset ranging from 24 months (North Europe) to 48 months (South Asia). Discussion: This review sets the background for a collaborative study involving a wide international consortium to perform with a standard methodology an investigation of the link between ancestry, environment, and ALS phenotype.