Intronic Haplotypes in the GBA Gene Do Not Predict Age at Diagnosis of Parkinson's Disease

Abstract

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p> <jats:italic>GBA</jats:italic> mutations are a common risk factor for Parkinson's disease (PD). A recent study has suggested that <jats:italic>GBA</jats:italic> haplotypes, identified by intronic variants, can affect age at diagnosis of PD.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>In this study, we assess this hypothesis using long reads across a large cohort and the publicly available Accelerating Medicines Partnership–Parkinson's Disease (AMP‐PD) cohort.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We recruited a PD cohort through the Remote Assessment of Parkinsonism Supporting Ongoing Development of Interventions in Gaucher Disease study (RAPSODI) and sequenced <jats:italic>GBA</jats:italic> using Oxford Nanopore technology. Genetic and clinical data on the full AMP‐PD cohort were obtained from the online portal of the consortium.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 1417 participants were analyzed. There was no significant difference in age at PD diagnosis between the two main haplotypes of the <jats:italic>GBA</jats:italic> gene.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> <jats:italic>GBA</jats:italic> haplotypes do not affect age at diagnosis of PD in the two independent cohorts studied. © 2021 The Authors. <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society</jats:p></jats:sec>