Attention-Deficit/Hyperactivity Disorder Genomics: Update for Clinicians

被引:22
作者
Elia, Josephine [1 ]
Sackett, Jillan [2 ]
Turner, Terri [2 ]
Schardt, Martin [3 ]
Tang, Shih-Ching
Kurtz, Nicole [2 ]
Dunfey, Maura [2 ]
McFarlane, Nadia A. [2 ]
Susi, Aita [2 ]
Danish, David [2 ]
Li, Alice [2 ]
Nissley-Tsiopinis, Jenelle [2 ]
Borgmann-Winter, Karin [2 ]
机构
[1] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Ctr Sci, Dept Child & Adolescent Psychiat, Philadelphia, PA 19104 USA
[3] Trinity Coll, Hartford, CT 06106 USA
基金
美国国家卫生研究院;
关键词
Attention-deficit/hyperactivity disorder; ADHD; Genetics; Epigenetics; Structural variants; Copy number variation; Pharmacogenetics; ADHD comorbidity; Ethics/laws; DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; LONGITUDINAL GENETIC-ANALYSIS; MATERNAL SMOKING; ADHD-SYMPTOMS; ENVIRONMENTAL CONTRIBUTIONS; WIDE ASSOCIATION; METHYLPHENIDATE TREATMENT; PSYCHIATRIC-DISORDERS; ATOMOXETINE OVERDOSE;
D O I
10.1007/s11920-012-0309-4
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Attention deficit, hyperactivity disorder (ADHD) is familial and highly heritable. Several candidate genes involved in neurotransmission have been identified, however these confer minimal risk, suggesting that for the most part, ADHD is not caused by single common genetic variants. Advances in genotyping enabling investigation at the level of the genome have led to the discovery of rare structural variants suggesting that ADHD is a genomic disorder, with potentially thousands of variants, and common neuronal pathways disrupted by numerous rare variants resulting in similar ADHD phenotypes. Heritability studies in humans also indicate the importance of epigenetic factors, and animal studies are deciphering some of the processes that confer risk during gestation and throughout the post-natal period. These and future discoveries will lead to improved diagnosis, individualized treatment, cures, and prevention. These advances also highlight ethical and legal issues requiring management and interpretation of genetic data and ensuring privacy and protection from misuse.
引用
收藏
页码:579 / 589
页数:11
相关论文
共 132 条
[61]   Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design [J].
Knopik, Valerie S. ;
Heath, Andrew C. ;
Jacob, Theodore ;
Slutske, Wendy S. ;
Bucholz, Kathleen K. ;
Madden, Pamela A. F. ;
Waldron, Mary ;
Martin, Nicholas G. .
PSYCHOLOGICAL MEDICINE, 2006, 36 (10) :1461-1471
[62]   Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study [J].
Knopik, VS ;
Sparrow, EP ;
Madden, PAF ;
Bucholz, KK ;
Hudziak, JJ ;
Reich, W ;
Slutske, WS ;
Grant, JD ;
McLaughlin, TL ;
Todorov, A ;
Todd, RD ;
Heath, AC .
PSYCHOLOGICAL MEDICINE, 2005, 35 (05) :625-635
[63]   Maternal smoking and hyperactivity in 8-year-old children [J].
Kotimaa, AJ ;
Moilanen, I ;
Taanila, A ;
Ebeling, F ;
Smalley, SL ;
McGough, JJ ;
Hartikainen, AL ;
Järvelin, MR .
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 2003, 42 (07) :826-833
[64]   Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice [J].
Kraft, Michael ;
Cirstea, Ion Cristian ;
Voss, Anne Kathrin ;
Thomas, Tim ;
Goehring, Ina ;
Sheikh, Bilal N. ;
Gordon, Lavinia ;
Scott, Hamish ;
Smyth, Gordon K. ;
Ahmadian, Mohammad Reza ;
Trautmann, Udo ;
Zenker, Martin ;
Tartaglia, Marco ;
Ekici, Arif ;
Reis, Andre ;
Doerr, Helmuth-Guenther ;
Rauch, Anita ;
Thiel, Christian Thomas .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (09) :3479-3491
[65]   Brain development and ADHD [J].
Krain, Amy L. ;
Castellanos, F. Xavier .
CLINICAL PSYCHOLOGY REVIEW, 2006, 26 (04) :433-444
[66]   Genetic influences on the stability of attention-deficit/hyperactivity disorder symptoms from early to middle childhood [J].
Kuntsi, J ;
Rijsdijk, F ;
Ronald, A ;
Asherson, P ;
Plomin, R .
BIOLOGICAL PSYCHIATRY, 2005, 57 (06) :647-654
[67]  
Langley K, 2005, Minerva Pediatr, V57, P359
[68]   Childhood attention-deficit hyperactivity disorder as an extreme of a continuous trait: a quantitative genetic study of 8,500 twin pairs [J].
Larsson, Henrik ;
Anckarsater, Henrik ;
Rastam, Maria ;
Chang, Zheng ;
Lichtenstein, Paul .
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY, 2012, 53 (01) :73-80
[69]   Genetic and environmental contributions to stability and change of ADHD symptoms between 8 and 13 years of age: A longitudinal twin study [J].
Larsson, JO ;
Larsson, H ;
Lichtenstein, P .
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 2004, 43 (10) :1267-1275
[70]   Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree [J].
Lesch, K-P ;
Selch, S. ;
Renner, T. J. ;
Jacob, C. ;
Nguyen, T. T. ;
Hahn, T. ;
Romanos, M. ;
Walitza, S. ;
Shoichet, S. ;
Dempfle, A. ;
Heine, M. ;
Boreatti-Huemmer, A. ;
Romanos, J. ;
Gross-Lesch, S. ;
Zerlaut, H. ;
Wultsch, T. ;
Heinzel, S. ;
Fassnacht, M. ;
Fallgatter, A. ;
Allolio, B. ;
Schaefer, H. ;
Warnke, A. ;
Reif, A. ;
Ropers, H-H ;
Ullmann, R. .
MOLECULAR PSYCHIATRY, 2011, 16 (05) :491-503