Candidate Genes
Candidate Genes
Genes Implicated in the Etiology of ADHD
The aim of scientific research into any disorder is to identify the causative factors. These factors can be genetic, environmental or a mixture of both. Also the genetic and environmental factors may interract with each other in ways which are confusing to investigation. Unfortunately, ADHD is one such disorder in which the etiology appears to be due to a mixture of environment and genetics. Not only that but it would appear to be polygenic in that inheritance is due a combination of many genes. This makes locating the genetic influences on ADHD all the more difficult as each gene involved may have only a small effect and thus be very dificult to detect. Also there may not be a gene which on its own is enough to always bring about ADHD syptomatology.
Many genetic studies have been performed nonetheless and many candidate genes found in various pathways including the dopamine system, the serotonin system, and the adrenalin system. To date the most commonly replicated associations are with the DAT1 and DRD4 genes in the dopamine system (see Brookes et al, 2006 here). Recently, two new loci have been associated with ADHD, namely monoamine oxidase A (MAO-A) and adrenergic alpha2A receptor gene (ADRA2A). While the first two genes have been very well explored over several years, these latter two have only really been implicated in publications since 2006 and more replicative work needs to be done to confirm the findings made so far. In addition to these genes, another four commonly named in the ADHD literature are 5-HTT, DBH, DRD5, and SNAP-25 (See Faraone & Khan 2006 review here). Good evidence exists for all of these but not to the same extent as for DAT1 and DRD4 in that there has been less clear replication.
Below are details of the above genes arranged as follows:
- Gene: The gene name and chromosomal location
- Allele: The allele linked to ADHD
- Ensembl: A diagram showing the position of the gene on its chromosome on the Ensembl site
- Genecard: A table showing information about the gene from the Weizmann Institute's Genecard database
- Recent Reference: Link to the abstract of the most recently published paper investigating the gene
Gene: DAT1 at 5p15.3
Allele: 480bp long
[Ensembl picture] [Genecard]
Recent Reference:
Neuromolecular Med. 2006;8(4):461-84 (Abstract)
Attention deficit hyperactivity disorder.
Kuntsi J, McLoughlin G, Asherson P.
Gene: DRD4 at 11p15.5
Allele: 7-repeat and 120-bp duplication
[Ensembl picture] [Genecard]
Recent References:
Am J Med Genet B Neuropsychiatr Genet. 2007 Apr 5;144(3):379-82 (Abstract)
Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): An update.
Gornick MC, Addington A, Shaw P, Bobb AJ, Sharp W, Greenstein D, Arepalli S, Castellanos FX, Rapoport JL.
Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144(2):231-6 (Abstract)
Association between the 120-bp duplication of the dopamine D4 receptor gene and attention deficit hyperactivity disorder: Genetic and molecular analyses.
Kereszturi E, Kiraly O, Csapo Z, Tarnok Z, Gadoros J, Sasvari-Szekely M, Nemoda Z.
Gene: MAO-A at Xp11.23
Allele: G-allele of 941G/T SNP
[Ensembl picture] [Genecard]
Recent Reference:
BMC Psychiatry. 2007 Feb 28;7:10 (Full)
Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples.
Xu X, Brookes K, Chen CK, Huang YS, Wu YY, Asherson P.
Gene: ADRA2A at 10q25.2
Allele: G-allele of 1291C/G SNP
[Ensembl picture] [Genecard]
Recent Reference:
Arch Gen Psychiatry. 2007 Feb;64(2):218-24 (Abstract)
Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder.
Polanczyk G, Zeni C, Genro JP, Guimaraes AP, Roman T, Hutz MH, Rohde LA.
Gene: 5-HTT at 17q11.2
Allele: 5-HTTLPR, and VNTR in intron 2, a SNP in the 3' untranslated region.
[Ensembl picture] [Genecard]
Recent References:
J Clin Psychiatry. 2006;67 Suppl 8:13-20 (Abstract)
Candidate gene studies of attention-deficit/hyperactivity disorder.
Faraone S, Khan S.
J Neural Transm. 2007 Apr;114(4):513-21 (Abstract)
Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample.
Heiser P, Dempfle A, Friedel S, Konrad K, Hinney A, Kiefl H, Walitza S, Bettecken T, Saar K, Linder M, Warnke A, Herpertz-Dahlmann B, Schafer H, Remschmidt H, Hebebrand J.
Gene: DBH at 9q34.2
Allele: TaqI A2 allele
[Ensembl picture] [Genecard]
Recent References:
Cortex. 2006 Aug;42(6):838-45 (Abstract)
The cognitive genetics of attention deficit hyperactivity disorder (ADHD): sustained attention as a candidate phenotype.
Bellgrove MA, Hawi Z, Gill M, Robertson IH.
Am J Med Genet B Neuropsychiatr Genet. 2006 Jul 5;141(5):487-98 (Abstract)
An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40 bp VNTR) in hyperactive and normal children followed to adulthood.
Barkley RA, Smith KM, Fischer M, Navia B.
Gene: DRD5 at 4p16.1
Allele: 148 bp
[Ensembl picture] [Genecard]
Recent References:
Clin Psychol Rev. 2006 Aug;26(4):396-432 (Abstract)
The genetics of attention deficit hyperactivity disorder.
Waldman I, Gizer I.
Hum Mol Genet. 2006 Jul 15;15(14):2276-84 (Abstract)
Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD).
Li D, Sham P, Owen M, He L.
Gene: SNAP-25 at 20p11.2 or 20p12.3
Allele: Dde1 polymorphisms
[Ensembl picture] [Genecard]
Recent References:
Am J Med Genet B Neuropsychiatr Genet. 2005 Apr 5;134(1):115-8 (Abstract)
DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention deficit hyperactivity disorder: no evidence for association.
Xu X, Knight J, Brookes K, Mill J, Sham P, Craig I, Taylor E, Asherson P.
Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133(1):68-73 (Abstract)
Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP-25, and 5HT1B.
Mill J, Xu X, Ronald A, Curran S, Price T, Knight J, Craig I, Sham P, Plomin R, Asherson P.
