The investigators and others have previously established that there is a 2-3 fold increase in the risk of idiopathic Parkinson s disease (PD) in first-degree relatives of probands with PD compared to first-degree relatives of controls. The recent identification of a mutation in the alpha-synuclein gene is the first confirmation of a genetic etiology for PD, although this mutation is associated with young age at onset and most likely will account for a very small proportion of familial PD. PD, like Alzheimer's disease may be genetically heterogeneous and different genetic mechanisms may underlie the familial aggregation. Careful inquiry into whether there are clinical phenotypes that are more often associated with a genetic susceptibility to PD and determination of the most likely mode of inheritance of these phenotypes has important implications for the design of genetic linkage studies. The investigators propose to determine whether genetic influences are greater in families of probands with early-onset PD (less than or = 50 years) compared to late-onset PD (greater than 50 years) tremor-dominant PD compared to postural instability gait disorder (PIGD) PD. The investigators will also test (1) whether the increased risk in first- degree relatives is specific for development of these clinically defined subtypes of PD and (2) whether or not the genetic susceptibility to PD also raises risk for essential tremor. The investigators will conduct two separate case-control studies simultaneously. Study I is a family study of 300 PD patients from the multi-ethnic community of Washington Heights-Inwood. The 300 controls for these patients will be drawn from two existing cohorts of community controls. Study 2 is a family study of 200 PD patients with age of onset less than or = 50) and 200 PD patients with age of onset greater than 50 who attend the service-based Center for Parkinson's Disease at Columbia University. 400 controls will be recruited by random digit dialing using the same area codes and exchanges as the patients and frequency matching on age, gender, ethnicity and education. All first-degree relatives will be interviewed by telephone and those who screen positive for PD or ET will be examined, as will a random sample of 200 screen-negative relatives. The investigators will also determine whether or not the cumulative incidence of P to age 90 is higher in relatives of cases from the service-based sample than in relatives of cases from the community-based sample, and if so, whether this is due to sensitivity of reporting or whether the service-based sample contains a higher proportion of familial cases because of a higher proportion of cases with clinical characteristics associated with a high familial risk. The investigators will use segregation analysis to determine the most likely mode of inheritance of these clinical phenotypes in order to determine the optimal strategy for a future genetic linkage study.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Oliver, Eugene J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Schools of Medicine
New York
United States
Zip Code
Alcalay, R N; Wolf, P; Levy, O A et al. (2018) Alpha galactosidase A activity in Parkinson's disease. Neurobiol Dis 112:85-90
Benito-León, Julián; Mato-Abad, Virginia; Louis, Elan D et al. (2017) White matter microstructural changes are related to cognitive dysfunction in essential tremor. Sci Rep 7:2978
Lee, Annie J; Wang, Yuanjia; Alcalay, Roy N et al. (2017) Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry. Mov Disord 32:1432-1438
Serrano, J Ignacio; Romero, Juan P; Castillo, Ma Dolores Del et al. (2017) A data mining approach using cortical thickness for diagnosis and characterization of essential tremor. Sci Rep 7:2190
Lee, Annie J; Marder, Karen; Alcalay, Roy N et al. (2017) Estimation of genetic risk function with covariates in the presence of missing genotypes. Stat Med 36:3533-3546
Alcalay, Roy N; Levy, Oren A; Wolf, Pavlina et al. (2016) SCARB2 variants and glucocerebrosidase activity in Parkinson's disease. NPJ Parkinsons Dis 2:
Swan, Matthew; Doan, Nancy; Ortega, Robert A et al. (2016) Neuropsychiatric characteristics of GBA-associated Parkinson disease. J Neurol Sci 370:63-69
Terrelonge Jr, Mark; Marder, Karen S; Weintraub, Daniel et al. (2016) CSF ?-Amyloid 1-42 Predicts Progression to Cognitive Impairment in Newly Diagnosed Parkinson Disease. J Mol Neurosci 58:88-92
Benito-León, Julián; Louis, Elan D; Mato-Abad, Virginia et al. (2016) In vivo neurometabolic profiling in orthostatic tremor. Medicine (Baltimore) 95:e4848
Shin, Hyeeun; Lee, Dong-Kyun; Lee, Jong-Min et al. (2016) Atrophy of the Cerebellar Vermis in Essential Tremor: Segmental Volumetric MRI Analysis. Cerebellum 15:174-81

Showing the most recent 10 out of 116 publications