Genome-wide survey implicates the influence of copy number variants (CNVs) in the development of early-onset bipolar disorder

被引：0
作者：
L Priebe
F A Degenhardt
S Herms
B Haenisch
M Mattheisen
V Nieratschker
M Weingarten
S Witt
R Breuer
T Paul
M Alblas
S Moebus
M Lathrop
M Leboyer
S Schreiber
M Grigoroiu-Serbanescu
W Maier
P Propping
M Rietschel
M M Nöthen
S Cichon
T W Mühleisen
机构：
[1] Life and Brain Center,Department of Genomics
[2] University of Bonn,Division of Genetic Epidemiology in Psychiatry
[3] Institute of Human Genetics,Department of Psychiatry
[4] University of Bonn,Department of Psychiatry
[5] Institute for Medical Biometry,undefined
[6] Informatics,undefined
[7] and Epidemiology,undefined
[8] University of Bonn,undefined
[9] Central Institute of Mental Health,undefined
[10] Institute for Medical Informatics,undefined
[11] Biometry and Epidemiology,undefined
[12] University Clinic Essen,undefined
[13] Centre National de Génotypage,undefined
[14] Institut Génomique,undefined
[15] INSERM U-513,undefined
[16] Faculté de Médecine,undefined
[17] University of Paris,undefined
[18] Faculty of Medicine,undefined
[19] AP-HP,undefined
[20] Albert Chenevier and Henri Mondor Hospitals,undefined
[21] Institute of Clinical Molecular Biology,undefined
[22] Christian Albrechts University,undefined
[23] Biometric Psychiatric Genetics Research Unit,undefined
[24] Alexandru Obregia Clinical Psychiatric Hospital,undefined
[25] University of Bonn,undefined
[26] Institute of Neuroscience and Medicine (INM-1),undefined
[27] Structural and Functional Organization of the Brain,undefined
[28] Genomic Imaging,undefined
[29] Research Center Juelich,undefined
来源：
Molecular Psychiatry | 2012年 / 17卷
关键词：
bipolar disorder; copy number variant; genome-wide burden; early age-at-onset; association;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
We used genome-wide single nucleotide polymorphism (SNP) data to search for the presence of copy number variants (CNVs) in 882 patients with bipolar disorder (BD) and 872 population-based controls. A total of 291 (33%) patients had an early age-at-onset ⩽21 years (AO⩽21years). We systematically filtered for CNVs that cover at least 30 consecutive SNPs and which directly affect at least one RefSeq gene. We tested whether (a) the genome-wide burden of these filtered CNVs differed between patients and controls and whether (b) the frequency of specific CNVs differed between patients and controls. Genome-wide burden analyses revealed that the frequency and size of CNVs did not differ substantially between the total samples of BD patients and controls. However, separate analysis of patients with AO⩽21years and AO>21years showed that the frequency of microduplications was significantly higher (P=0.0004) and the average size of singleton microdeletions was significantly larger (P=0.0056) in patients with AO⩽21years compared with controls. A search for specific BD-associated CNVs identified two common CNVs: (a) a 160 kb microduplication on 10q11 was overrepresented in AO⩽21years patients (9.62%) compared with controls (3.67%, P=0.0005) and (b) a 248 kb microduplication on 6q27 was overrepresented in the AO⩽21years subgroup (5.84%) compared with controls (2.52%, P=0.0039). These data suggest that CNVs have an influence on the development of early-onset, but not later-onset BD. Our study provides further support for previous hypotheses of an etiological difference between early-onset and later-onset BD.
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页码：421 / 432
页数：11
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