Association of long ATXN2 CAG repeat sizes with increased risk of amyotrophic lateral sclerosis.

OBJECTIVE To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS. DESIGN Case-control study. SETTING France and Quebec, Canada. PARTICIPANTS A total of 556 case patients with ALS and 471 healthy controls; both groups of participants are of French or French-Canadian origin. RESULTS We observed a significant association between ATXN2 high-length alleles (≥29 CAG repeats) and ALS in French and French-Canadian ALS populations. Furthermore, we identified spinocerebellar ataxia type 2-pathogenic polyglutamine expansions (≥32 CAG repeats) in both familial and sporadic ALS cases. CONCLUSIONS Altogether, our findings support ATXN2 high-length repeats as a risk factor for ALS and further indicate a genetic link between spinocerebellar ataxia type 2 and ALS.