Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies

被引：288

作者：

Lesch, Klaus-Peter ^{[1
]}

Timmesfeld, Nina ^{[5
]}

Renner, Tobias J. ^{[2
]}

Halperin, Rebecca ^{[6
]}

Roeser, Christoph ^{[1
]}

Nguyen, T. Trang ^{[5
]}

Craig, David W. ^{[6
]}

Romanos, Jasmin ^{[1
,2
]}

Heine, Monika ^{[1
]}

Meyer, Jobst ^{[3
]}

Freitag, Christine ^{[4
]}

Warnke, Andreas ^{[2
]}

Romanos, Marcel ^{[2
]}

Schaefer, Helmut ^{[5
]}

Walitza, Susanne ^{[2
]}

Reif, Andreas ^{[1
]}

Stephan, Dietrich A. ^{[6
]}

Jacob, Christian ^{[1
]}

机构：

[1] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, ADHD Clin Res Program Mol & Clin Psychobiol, D-97080 Wurzburg, Germany

[2] Univ Wurzburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, ADHD Clin Res Program, D-97080 Wurzburg, Germany

[3] Univ Trier, Dept Neurobehav Genet, Trier, Germany

[4] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Homburg, Germany

[5] Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany

[6] Translat Genom Res Inst, TGen, Neurogenom Div, Phoenix, AZ USA

来源：

JOURNAL OF NEURAL TRANSMISSION | 2008年 / 115卷 / 11期

关键词：

Attention-deficit/hyperactivity disorder; Adult ADHD; Drug abuse; Substance use disorder; Genome-wide association; GWA; Pooled DNA; 500K SNP array; 50K SNP array; Linkage; Candidate genes; Cell adhesion; Signal transduction; Synaptic plasticity;

D O I：

10.1007/s00702-008-0119-3

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

A genome-wide association (GWA) study with pooled DNA in adult attention-deficit/hyperactivity disorder (ADHD) employing similar to 500K SNP markers identifies novel risk genes and reveals remarkable overlap with findings from recent GWA scans in substance use disorders. Comparison with results from our previously reported high-resolution linkage scan in extended pedigrees confirms several chromosomal loci, including 16q23.1-24.3 which also reached genome-wide significance in a recent meta-analysis of seven linkage studies (Zhou et al. in Am J Med Genet Part B, 2008). The findings provide additional support for a common effect of genes coding for cell adhesion molecules (e.g., CDH13, ASTN2) and regulators of synaptic plasticity (e.g., CTNNA2, KALRN) despite the complex multifactorial etiologies of adult ADHD and addiction vulnerability.

引用

页码：1573 / 1585

页数：13

共 57 条

[1]

Adams NC, 2002, DEVELOPMENT, V129, P965

[2] Attention-deficit/hyperactivity disorder in a population isolate: Linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11 [J].

Arcos-Burgos, M ;

Castellanos, FX ;

Pineda, D ;

Lopera, F ;

Palacio, JD ;

Palacio, LG ;

Rapoport, JL ;

Berg, K ;

Bailey-Wilson, JE ;

Muenke, M .

AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (06) :998-1014

[3] A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: Suggestive evidence for linkage on chromosomes 7p and 15q [J].

Bakker, SC ;

van der Meulen, EM ;

Buitelaar, JK ;

Sandkuijl, LA ;

Pauls, DL ;

Monsuur, AJ ;

van't Slot, R ;

Minderaa, RB ;

Gunning, WB ;

Pearson, PL ;

Sinke, RJ .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (05) :1251-1260

[4] 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

[5] 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

[6]

Butcher LM, 2008, GENES BRAIN BEHAV, V7, P435, DOI 10.1111/j.1601-183X.2007.00368.x

[7] Cell adhesion molecules: signalling functions at the synapse [J].

Dalva, Matthew B. ;

McClelland, Andrew C. ;

Kayser, Matthew S. .

NATURE REVIEWS NEUROSCIENCE, 2007, 8 (03) :206-220

[8] Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action [J].

Deng, YP ;

Bhattacharya, S ;

Swamy, OR ;

Tandon, RC ;

Wang, Y ;

Janda, R ;

Riedel, H .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (41) :39311-39322

[9] Applicability of DNA pools on 500 KSNP microarrays for cost-effective initial screens in genomewide association studies [J].

Docherty, Sophia J. ;

Butcher, Lee M. ;

Schalkwyk, Leonard C. ;

Plomin, Robert .

BMC GENOMICS, 2007, 8 (1)

[10] Whole-genome analysis of sporadic amyotrophic lateral sclerosis [J].

Dunckley, Travis ;

Huentelman, Matthew J. ;

Craig, David W. ;

Pearson, John V. ;

Szelinger, Szabolcs ;

Joshipura, Keta ;

Halperin, Rebecca F. ;

Stamper, Chelsea ;

Jensen, Kendall R. ;

Letizia, David ;

Hesterlee, Sharon E. ;

Pestronk, Alan ;

Levine, Todd ;

Bertorini, Tulio ;

Graves, Michael C. ;

Mozaffar, Tahseen ;

Jackson, Carlayne E. ;

Bosch, Peter ;

McVey, April ;

Dick, Arthur ;

Barohn, Richard ;

Lomen-Hoerth, Catherine ;

Rosenfeld, Jeffrey ;

O'Connor, Daniel T. ;

Zhang, Kuixing ;

Crook, Richard ;

Ryberg, Henrik ;

Hutton, Michael ;

Katz, Jonathan ;

Simpson, Ericka P. ;

Mitsumoto, Hiroshi ;

Bowser, Robert ;

Miller, Robert G. ;

Appel, Stanley H. ;

Stephan, Dietrich A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (08) :775-788

← 1 2 3 4 5 6 →