Comprehensive assessment of PINK1 variants in Parkinson's disease

• Published in: Neurobiology of aging Vol. 91; pp. 168.e1 - 168.e5
• Main Authors: Krohn, Lynne, Grenn, Francis P., Makarious, Mary B., Kim, Jonggeol Jeffrey, Bandres-Ciga, Sara, Roosen, Dorien A., Gan-Or, Ziv, Nalls, Mike A., Singleton, Andrew B., Blauwendraat, Cornelis
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2020
• Subjects: Adult; Aged; Aged, 80 and over; Datasets as Topic; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Heterozygote; Heterozygous carriers; Humans; Male; Membrane Proteins; Middle Aged; Mutation; Negative Results; p.G411S; Parkinson Disease - genetics; Parkinson's disease; Parkinsonian Disorders - genetics; PINK1; Protein Kinases - genetics; Risk factor; Risk Factors; Tumor Suppressor Proteins; p.G411S; Heterozygous carriers; PINK1; Parkinson's disease; Risk factor
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2020.03.003

Multiple genes have been associated with monogenic Parkinson's disease and Parkinsonism syndromes. Mutations in PINK1 (PARK6) have been shown to result in autosomal recessive early-onset Parkinson's disease. In the past decade, several studies have suggested that carrying a single heterozygous PINK1 mutation is associated with increased risk for Parkinson's disease. Here, we comprehensively assess the role of PINK1 variants in Parkinson's disease susceptibility using several large data sets totalling 376,558 individuals including 13,708 cases with Parkinson's disease and 362,850 control subjects. After combining these data, we did not find evidence to support a role for heterozygous PINK1 mutations as a robust risk factor for Parkinson's disease. •Large-scale case-control analysis of pathogenic heterozygous PINK1 carriers does not support increased Parkinson's risk.•Heterozygous p.G411S is not a robust risk factor for Parkinson's disease.•Parkinson's p.G411S carriers did not tend to have a second deleterious PINK1 mutation.