Convergent Genome Wide Association Results for Bipolar Disorder and Substance Dependence

被引:40
作者
Johnson, Catherine [1 ]
Drgon, Tomas [1 ]
McMahon, Francis J. [2 ]
Uhl, George R. [1 ]
机构
[1] NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD USA
[2] Mood & Anxiety Disorders Program, Unit Genet Basis Mood & Anxiety Disorders, Bethesda, MD USA
基金
英国惠康基金;
关键词
complex genetics; addiction; depressive disorder; single nucleotide polymorphism; ADDICTION MOLECULAR-GENETICS; VULNERABILITY LOCI; VALIDATION; GENES; MOOD; RDC;
D O I
10.1002/ajmg.b.30900
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Twin studies document substantial heritability for substance dependence and bipolar disorder [Shih et a]. (2004); Uhl et al. (2008a)]. Individuals with bipolar disorder display substance use disorders at rates that are much higher than those in the general population [Krishnan (2005)]. We Would thus predict: 1) substantial overlap between different genome wide association (GWA) studies of bipolar disorder 2) significant overlap between results from bipolar disorder and substance dependence. Recent GWA studies [Baum et al. (2007); Sklar et al. (2008); Uhl et al. (2008a); Wellcome Trust Consortium (2007)] allow us to test these ideas, although 1) these datasets display difficult features that include use of differing sets of SNPs, likely polyenic,9 genetics, likely differences in linkage disequilibrium between samples, heterogeneity both between and within loci and 2) several, though not all, reports have failed to identify any allele of any single nucleotide polymorphism (SNP) ("same SNP same allele") that is reproducibly associated with bipolar disorder with "genome wide" significance. We now report analyses that identify clustered, P< 0.05 SNPs within genes that overlap between the bipolar samples (Monte Carlo P < 0.00001). Overlapping data from at least three of these studies identify 69 genes. 23 of these genes also contain overlapping clusters of nominally-positive SNPs for substance dependence. Variants in these "addiction/bipolar" genes are candidates to influence the brain in ways that manifest as enhanced vulnerabilites to both substance dependence and bipolar disorder. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:182 / 190
页数:9
相关论文
共 25 条
[1]   Meta-analysis of two genome-wide association studies of bipolar disorder reveals important points of agreement [J].
Baum, A. E. ;
Hamshere, M. ;
Green, E. ;
Cichon, S. ;
Rietschel, M. ;
Noethen, M. M. ;
Craddock, N. ;
McMahon, F. J. .
MOLECULAR PSYCHIATRY, 2008, 13 (05) :466-467
[2]   A genome-wide association study implicates diacylglycerol kinase η (DGKH) and several other genes in the etiology of bipolar disorder [J].
Baum, A. E. ;
Akula, N. ;
Cabanero, M. ;
Cardona, I. ;
Corona, W. ;
Klemens, B. ;
Schulze, T. G. ;
Cichon, S. ;
Rietschel, M. ;
Noethen, M. M. ;
Georgi, A. ;
Schumacher, J. ;
Schwarz, M. ;
Abou Jamra, R. ;
Hoefels, S. ;
Propping, P. ;
Satagopan, J. ;
Detera-Wadleigh, S. D. ;
Hardy, J. ;
McMahon, F. J. .
MOLECULAR PSYCHIATRY, 2008, 13 (02) :197-207
[3]   Parsing the association between bipolar, conduct, and substance use disorders: A familial risk analysis [J].
Biederman, J ;
Faraone, SV ;
Wozniak, J ;
Monuteaux, MC .
BIOLOGICAL PSYCHIATRY, 2000, 48 (11) :1037-1044
[4]   Novel genes identified in a high-density genome wide association study for nicotine dependence [J].
Bierut, Laura Jean ;
Madden, Pamela A. F. ;
Breslau, Naomi ;
Johnson, Eric O. ;
Hatsukami, Dorothy ;
Pomerleau, Ovide F. ;
Swan, Gary E. ;
Rutter, Joni ;
Bertelsen, Sarah ;
Fox, Louis ;
Fugman, Douglas ;
Goate, Alison M. ;
Hinrichs, Anthony L. ;
Konvicka, Karel ;
Martin, Nicholas G. ;
Montgomery, Grant W. ;
Saccone, Nancy L. ;
Saccone, Scott F. ;
Wang, Jen C. ;
Chase, Gary A. ;
Rice, John P. ;
Ballinger, Dennis G. .
HUMAN MOLECULAR GENETICS, 2007, 16 (01) :24-35
[5]   Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].
Burton, Paul R. ;
Clayton, David G. ;
Cardon, Lon R. ;
Craddock, Nick ;
Deloukas, Panos ;
Duncanson, Audrey ;
Kwiatkowski, Dominic P. ;
McCarthy, Mark I. ;
Ouwehand, Willem H. ;
Samani, Nilesh J. ;
Todd, John A. ;
Donnelly, Peter ;
Barrett, Jeffrey C. ;
Davison, Dan ;
Easton, Doug ;
Evans, David ;
Leung, Hin-Tak ;
Marchini, Jonathan L. ;
Morris, Andrew P. ;
Spencer, Chris C. A. ;
Tobin, Martin D. ;
Attwood, Antony P. ;
Boorman, James P. ;
Cant, Barbara ;
Everson, Ursula ;
Hussey, Judith M. ;
Jolley, Jennifer D. ;
Knight, Alexandra S. ;
Koch, Kerstin ;
Meech, Elizabeth ;
Nutland, Sarah ;
Prowse, Christopher V. ;
Stevens, Helen E. ;
Taylor, Niall C. ;
Walters, Graham R. ;
Walker, Neil M. ;
Watkins, Nicholas A. ;
Winzer, Thilo ;
Jones, Richard W. ;
McArdle, Wendy L. ;
Ring, Susan M. ;
Strachan, David P. ;
Pembrey, Marcus ;
Breen, Gerome ;
St Clair, David ;
Caesar, Sian ;
Gordon-Smith, Katherine ;
Jones, Lisa ;
Fraser, Christine ;
Green, Elain K. .
NATURE, 2007, 447 (7145) :661-678
[6]  
Ferreira MA., 2008, NAT GENET
[7]   Genome-wide association in bipolar [J].
Gershon, E. S. ;
Liu, C. ;
Badner, J. A. .
MOLECULAR PSYCHIATRY, 2008, 13 (01) :1-2
[8]   Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism [J].
Johnson, Catherine ;
Drgon, Tomas ;
Liu, Qing-Rong ;
Walther, Donna ;
Edenberg, Howard ;
Rice, John ;
Foroud, Tatiana ;
Uhl, George R. .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2006, 141B (08) :844-853
[9]   Psychiatric and medical comorbidities of bipolar disorder [J].
Krishnan, KRR .
PSYCHOSOMATIC MEDICINE, 2005, 67 (01) :1-8
[10]   GENETIC DISSECTION OF COMPLEX TRAITS [J].
LANDER, ES ;
SCHORK, NJ .
SCIENCE, 1994, 265 (5181) :2037-2048