Variation of global DNA methylation levels with age and in autistic children.
BACKGROUND
The change in epigenetic signatures, in particular DNA methylation, has been proposed as risk markers for various age-related diseases. However, the course of variation in methylation levels with age, the difference in methylation between genders, and methylation-disease association at the whole genome level is unclear. In the present study, genome-wide methylation levels in DNA extracted from peripheral blood for 2116 healthy Chinese in the 2-97 age range and 280 autistic trios were examined using the fluorescence polarization-based genome-wide DNA methylation quantification method developed by us.


RESULTS
Genome-wide or global DNA methylation levels proceeded through multiple phases of variation with age, consisting of a steady increase from age 2 to 25 (r = 0.382) and another rise from age 41 to 55 to reach a peak level of ~80 % (r = 0.265), followed by a sharp decrease to ~40 % in the mid-1970s (age 56 to 75; r = -0.395) and leveling off thereafter. Significant gender effect in methylation levels was observed only for the 41-55 age group in which methylation in females was significantly higher than in males (p = 0.010). In addition, global methylation level was significantly higher in autistic children than in age-matched healthy children (p < 0.001).


CONCLUSIONS
The multiphasic nature of changes in global methylation levels with age was delineated, and investigation into the factors underlying this profile will be essential to a proper understanding of the aging process. Furthermore, this first report of global hypermethylation in autistic children also illustrates the importance of age-matched controls in characterization of disease-associated variations in DNA methylation.
Division of Life Science, Applied Genomics Centre and Centre for Statistical Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Shui-Ying
SY
Tsang
Division of Life Science, Applied Genomics Centre and Centre for Statistical Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Tanveer
T
Ahmad
Division of Life Science, Applied Genomics Centre and Centre for Statistical Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Flora W K
FW
Mat
Division of Life Science, Applied Genomics Centre and Centre for Statistical Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.|Department of Medical Genetics, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Cunyou
C
Zhao
Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China. xiaoshifu@msn.com.
Shifu
S
Xiao
The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, 410078, China. xiakuncsu@gmail.com.
Kun
K
Xia
Division of Life Science, Applied Genomics Centre and Centre for Statistical Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. hxue@ust.hk.
Hong
H
Xue
Aging; Autism spectrum disorder; CpG methylation; Developmental epigenetics; Genome-wide methylation quantification
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