title: Aberrant DNA methylation of blood in schizophrenia by adjusting for estimated cellular proportions.
abstract: DNA methylation, which is the transference of a methyl group to the 5'-carbon position of the cytosine in a CpG dinucleotide, is one of the major mechanisms of epigenetic modifications. A number of studies have demonstrated altered DNA methylation of peripheral blood cells in schizophrenia (SCZ) in previous studies. However, most of these studies have been limited to the analysis of the CpG sites in CpG islands in gene promoter regions, and cell-type proportions of peripheral leukocytes, which may be one of the potential confounding factors for DNA methylation, have not been adjusted in these studies. In this study, we performed a genome-wide DNA methylation profiling of the peripheral leukocytes from patients with SCZ and from non-psychiatric controls (N = 105; 63 SCZ and 42 control subjects) using a quantitative high-resolution DNA methylation microarray which covered across the whole gene region (485,764 CpG dinucleotides). In the DNA methylation data analysis, we first estimated the cell-type proportions of each sample with a published algorithm. Next, we performed a surrogate variable analysis to identify potential confounding factors in our microarray data. Finally, we conducted a multiple linear regression analysis in consideration of these factors, including estimated cell-type proportions, and identified aberrant DNA methylation in SCZ at 2,552 CpG loci at a 5% false discovery rate correction. Our results suggest that altered DNA methylation may be involved in the pathophysiology of SCZ, and cell heterogeneity adjustments may be necessary for DNA methylation analysis.
authors: Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-8-15, Kuramoto-cho, Tokushima, 770-8503, Japan, knst5511mkt@sunny.ocn.ne.jp.
authors: Makoto
authors: M
authors: Kinoshita
authors: Shusuke
authors: S
authors: Numata
authors: Atsushi
authors: A
authors: Tajima
authors: Kazutaka
authors: K
authors: Ohi
authors: Ryota
authors: R
authors: Hashimoto
authors: Shinji
authors: S
authors: Shimodera
authors: Issei
authors: I
authors: Imoto
authors: Masatoshi
authors: M
authors: Takeda
authors: Tetsuro
authors: T
authors: Ohmori
mesh_terms: D000328:Adult; D015986:Confounding Factors, Epidemiologic; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D015226:Dinucleoside Phosphates; D005260:Female; D055106:Genome-Wide Association Study; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism*; D016014:Linear Models; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics
chemical_list: D015226:Dinucleoside Phosphates; D011944:Receptors, Androgen; C015772:CpG dinucleotide