Person:
Berlyand, Yosef

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Berlyand

First Name

Yosef

Name

Berlyand, Yosef

Filters

20161

Settings

Author's Publications: search.filters.isAuthorOfPublication.3fcd4748-5089-40b8-8ff0-e5558f2f685d

Search Results

Now showing 1 - 1 of 1
  • Thumbnail Image
    Publication
    Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype
    (John Wiley and Sons Inc., 2016) Cooper, Christine A.; Jain, Nimansha; Gallagher, Michael D.; Weintraub, Daniel; Xie, Sharon X.; Berlyand, Yosef; Espay, Alberto J.; Quinn, Joseph; Edwards, Karen L.; Montine, Thomas; Van Deerlin, Vivianna M.; Trojanowski, John; Zabetian, Cyrus P.; Chen‐Plotkin, Alice S.
    Abstract Objective: Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. Methods: We screened 10 SNPs, previously associated with PD risk, for association with tremor‐dominant (TD) versus postural‐instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi‐site replication cohort of 559 PD patients. SNPs associated with motor phenotype in both cross‐sectional cohorts were next evaluated for association with (1) rates of motor progression in a longitudinal subgroup of 230 PD patients and (2) brain alpha‐synuclein (SNCA) expression in the GTEx (Genotype‐Tissue Expression project) consortium database. Results: Genotype at rs356182, near SNCA, correlated with the TD/PIGD ratio in both the discovery (Bonferroni‐corrected P = 0.04) and replication cohorts (P = 0.02). The rs356182 GG genotype was associated with a more tremor‐predominant phenotype and predicted a slower rate of motor progression (1‐point difference in annual rate of UPDRS‐III motor score change, P = 0.01). The rs356182 genotype was associated with SNCA expression in the cerebellum (P = 0.005). Interpretation Our study demonstrates that the GG genotype at rs356182 provides molecular definition for a clinically important endophenotype associated with (1) more tremor‐predominant motor phenomenology, (2) slower rates of motor progression, and (3) decreased brain expression of SNCA. Such molecularly defined endophenotyping in PD may benefit both clinical trial design and tailoring of clinical care as we enter the era of precision medicine.