DNA methylation age is not accelerated in brain or blood of subjects with schizophrenia

SCHIZOPHRENIA RESEARCH

卷:196

Article

McKinney, Brandon C.¹  Lin, Huang²  Ding, Ying²  Lewis, David A.¹  Sweet, Robert A.^1,3,4 

[1] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA

[2] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA

[4] VA Pittsburgh Healthcare Syst, VISN4 Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA

关键词: Schizophrenia;    Accelerated aging;    DNA methylation;    Epigenetic clock;    Aging;    Biomarkers;   

DOI  :  10.1016/j.schres.2017.09.025

来源: Elsevier

【 摘 要 】

Individuals with schizophrenia (SZ) exhibit multiple premature age-related phenotypes and die similar to 20 years prematurely. The accelerated aging hypothesis of SZ has been advanced to explain these observations, it posits that SZ-associated factors accelerate the progressive biological changes associated with normal aging. Testing the hypothesis has been limited by the absence of robust, meaningful, and multi-tissue measures of biological age. Recently, a method was described in which DNA methylation (DNAm) levels at 353 genomic sites are used to produce DNAm age, an estimate of biological age with advantages over existing measures. We used this method and 3 publicly-available DNAm datasets, 1 from brain and 2 from blood, to test the hypothesis. The brain dataset was composed of data from the dorsolateral prefrontal cortex of 232 non-psychiatric control (NPC) and 195 SZ subjects. Blood dataset #1 was composed of data from whole blood of 304 NPC and 332 SZ subjects, and blood dataset #2 was composed of data from whole blood of 405 NPC and 260 SZ subjects. DNAm age and chronological age correlated strongly (r = 0.92-0.95, p < 0.0001) in both NPC and SZ subjects in all 3 datasets. DNAm age acceleration did not differ between NPC and SZ subjects in the brain dataset (t - 0.52, p - 0.60), blood dataset #1 (t = 1.51, p = 0.13), or blood dataset #2 (t = 0.93, p = 0.35). Consistent with our previous findings from a smaller study of postmortem brains, our findings suggest there is no acceleration of brain or blood aging in SZ and, thus, do not support the accelerated aging hypothesis of SZ. (C) 2017 Elsevier B.V. All rights reserved.

【 授权许可】

Free