Authors: Heckman MG; Soto-Ortolaza AI; Diehl NN; Carrasquillo MM; Uitti RJ; Wszolek ZK; Graff-Radford NR; Ross OA

Abstract: BACKGROUND: A variety of definitions of successful aging have been proposed, many of which relate to longevity, freedom from disease and disability, or preservation of high physical and cognitive function. Many behavioral, biomedical, and psychological factors have been linked with these various measures of successful aging, however genetic predictors are less understood. Parkinson's disease (PD) is an age-related neurodegenerative disorder, and variants in the alpha-synuclein gene (SNCA) affect susceptibility to PD. This exploratory study examined whether SNCA variants may also promote successful aging as defined by survival without neurological disease. METHODS: We utilized 769 controls without neurological disease (Mean age: 79 years, Range: 33-99 years) and examined the frequency of 20 different SNCA variants across age groups using logistic regression models. We also included 426 PD cases to assess the effect of these variants on PD risk. RESULTS: There was a significant decline in the proportion of carriers of the minor allele of rs10014396 as age increased (P = 0.021), from 30% in controls younger than 60 to 14% in controls 90 years of age or older. Findings were similar for rs3775439, where the proportion of carriers of the minor allele declined from 32% in controls less than 60 years old to 19% in those 90 or older (P = 0.025). A number of SNCA variants, not including rs10014396 or rs3775439, were significantly associated with susceptibility to PD. CONCLUSIONS: In addition to its documented roles in PD and alpha-synucleinopathies, our results suggest that SNCA has a role in survival free of neurological disease. Acknowledging that our findings would not have withstood correction for multiple testing, validation in an independent series of aged neurologically normal controls is needed.

Keywords: Adult; Aged; Aged, 80 and over; Aging/*genetics; Female; *Health; Humans; Linkage Disequilibrium/genetics; Male; Middle Aged; Parkinson Disease/genetics; *Polymorphism, Single Nucleotide; alpha-Synuclein/*genetics
Journal: PloS one
Volume: 7
Issue: 8
Pages: e42877
Date: Aug. 23, 2012
PMID: 22912757
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Heckman MG, Soto-Ortolaza AI, Diehl NN, Carrasquillo MM, Uitti RJ, Wszolek ZK, Graff-Radford NR, Ross OA (2012) Evaluation of the role of SNCA variants in survival without neurological disease. PloS one 7: e42877.

Longevity Variant Associations (p-value):
  • rs10014396 (0.021)
  • rs3775439 (0.025)
  • rs356218 (0.53)
  • rs17180453 (0.63)
  • rs3775423 (0.9)
  • rs2736990 (0.31)
  • rs2572324 (0.41)
  • rs3796661 (0.59)
  • rs2737033 (0.27)
  • rs9995651 (0.98)
  • rs2583959 (0.21)
  • rs2737012 (0.21)
  • rs1372519 (0.19)
  • rs3756063 (0.54)
  • rs1372520 (0.22)
  • rs2619361 (0.26)
  • rs2619362 (0.27)
  • rs2301135 (0.79)
  • rs2619363 (0.24)
  • rs2583988 (0.26)

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