A multi-tissue analysis identifies HLA complex group 9 gene methylation differences in bipolar disorder

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Title:	A multi-tissue analysis identifies HLA complex group 9 gene methylation differences in bipolar disorder
Authors:	王孫崇;Kaminsky, Z;Tochigi, M;Jia, P;Pal, M;Mill, J;Kwan, A;Ioshikhes, I;Vincent, J B;Kennedy, J L;Strauss, J;Pai, S;Wang, S-C;Petronis, A
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	Addictions;Adult;Adult and adolescent clinical studies;Age;Age Factors;Behavioral Sciences;Biological and medical sciences;Biological Psychology;Bipolar Disorder;Bipolar Disorder - blood;Bipolar Disorder - genetics;Bipolar Disorder - metabolism;Bipolar disorders;Bisulfite;Brain;Brain - metabolism;Case-Control Studies;CpG islands;Development and progression;Disease;DNA Methylation;DNA Methylation - genetics;Epigenetics;Female;Gene mapping;Genes;Genetic aspects;Genetic testing;Genotype;Genotypes;Histocompatibility antigen HLA;Histocompatibility antigens;Histones;HLA histocompatibility antigens;Humans;Leukocytes;Male;Medical sciences;Medicine;Medicine & Public Health;Mental health;Methylation;Middle Aged;Mood disorders;Neurosciences;Nucleotide sequence;original-article;Peripheral blood;Pharmacotherapy;Physiological aspects;Polymorphism, Single Nucleotide;Psychiatry;Psychology. Psychoanalysis. Psychiatry;Psychopathology. Psychiatry;Psychosis;Risk factors;RNA, Long Noncoding;RNA, Untranslated;RNA, Untranslated - genetics;RNA, Untranslated - metabolism;Sodium;Sperm;Spermatozoa;Spermatozoa - metabolism;Statistical analysis
Date:	2012-07-01
Issue Date:	2026-04-23 11:14:45 (UTC+8)
Publisher:	Nature Publishing Group;London: Springer Science and Business Media LLC
Abstract:	摘要： Epigenetic studies of DNA and histone modifications represent a new and important activity in molecular investigations of human disease. Our previous epigenome-wide scan identified numerous DNA methylation differences in post-mortem brain samples from individuals affected with major psychosis. In this article, we present the results of fine mapping DNA methylation differences at the human leukocyte antigen (HLA) complex group 9 gene (HCG9) in bipolar disorder (BPD). Sodium bisulfite conversion coupled with pyrosequencing was used to interrogate 28 CpGs spanning ∼700 bp region of HCG9 in 1402 DNA samples from post-mortem brains, peripheral blood cells and germline (sperm) of bipolar disease patients and controls. The analysis of nearly 40 000 CpGs revealed complex relationships between DNA methylation and age, medication as well as DNA sequence variation (rs1128306). Two brain tissue cohorts exhibited lower DNA methylation in bipolar disease patients compared with controls at an extended HCG9 region (P=0.026). Logistic regression modeling of BPD as a function of rs1128306 genotype, age and DNA methylation uncovered an independent effect of DNA methylation in white blood cells (odds ratio (OR)=1.08, P=0.0077) and the overall sample (OR=1.24, P=0.0011). Receiver operating characteristic curve A prime statistics estimated a 69-72% probability of correct BPD prediction from a case vs control pool. Finally, sperm DNA demonstrated a significant association (P=0.018) with BPD at one of the regions demonstrating epigenetic changes in the post-mortem brain and peripheral blood samples. The consistent multi-tissue epigenetic differences at HCG9 argue for a causal association with BPD. 其他題名： Mol Psychiatry 出版者： London: Springer Science and Business Media LLC 出版日期： 2012-07-01 出處： Molecular Psychiatry, 2012-07, Vol.17 (7), p.728-740 資源來源： EBSCOhost Academic Search Premier 版權： Macmillan Publishers Limited 2012 版權： 2015 INIST-CNRS 版權： COPYRIGHT 2012 Nature Publishing Group 版權： Copyright Nature Publishing Group Jul 2012 版權： Macmillan Publishers Limited 2012. 識別號： ISSN: 1359-4184 識別號： ISSN: 1476-5578 識別號： EISSN: 1476-5578 識別號： DOI: 10.1038/mp.2011.64 識別號： PMID: 21647149
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] journal & Dissertation

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