Association Analysis of Candidate Genes for ADHD on Chromosomes 5p13, 6q12, 16p and 17p

Attention-deficit/hyperactivity disorder (ADHD) is a common, heterogeneous psychiatric disorder of childhood displaying inattentive, hyperactive, and impulsive symptoms. Although the biological basis of ADHD remains unknown, it has been shown that genetic factors substantially contribute to the aetiology of the disorder. Our group has previously reported significant linkage to four chromosomal regions on 5p13, 6q12, 16p13 and 17p11 in genome-wide scans and subsequent fine-mapping. We selected nine positional candidate genes within the linkage intervals for study based on bio- logical plausibility. We analyzed at least 189 ADHD trios to determine if common variants in these genes have a major af- fect on ADHD risk. None yielded significant association. This does however not completely exclude these genes as poten- tial susceptibility genes for ADHD since it is plausible for common causal variants with low effect size to go undetected due to insufficient power of the study sample. We conclude that none of the tested alleles confer a major risk for develop- ing ADHD and that investigation of other genes within the linked regions is warranted.

[1]  A. Philalithis,et al.  Variations in prevalence of attention deficit hyperactivity disorder worldwide , 2006, European Journal of Pediatrics.

[2]  K Konrad,et al.  A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairs , 2006, Molecular Psychiatry.

[3]  C. Francks,et al.  Pooled genome-wide linkage data on 424 ADHD ASPs suggests genetic heterogeneity and a common risk locus at 5p13 , 2006, Molecular Psychiatry.

[4]  C. Sabatti,et al.  Guidelines for association studies in Human Molecular Genetics. , 2005, Human molecular genetics.

[5]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[6]  J. Rapoport,et al.  Attention-Deficit/Hyperactivity Disorder in a Population Isolate: Linkage to Loci at 4q13.2, 5q33.3, 11q22, and 17p11 , 2022 .

[7]  C. Walsh,et al.  Mitotic Spindle Regulation by Nde1 Controls Cerebral Cortical Size , 2004, Neuron.

[8]  C. Francks,et al.  Attention Deficit Hyperactivity Disorder: Fine Mapping Supports Linkage to 5p13, 6q12, 16p13, and 17p11 , 2022 .

[9]  Jan K Buitelaar,et al.  Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes. , 2004, American journal of human genetics.

[10]  J. Fogel,et al.  Metabolite Changes Resulting From Treatment in Children With ADHD: A 1H-MRS Study , 2003, Clinical neuropharmacology.

[11]  P L Pearson,et al.  A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: suggestive evidence for linkage on chromosomes 7p and 15q. , 2003, American journal of human genetics.

[12]  C. Francks,et al.  A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11. , 2003, American journal of human genetics.

[13]  C. Francks,et al.  Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism. , 2002, American journal of human genetics.

[14]  C. Francks,et al.  A genomewide scan for loci involved in attention-deficit/hyperactivity disorder. , 2002, American journal of human genetics.

[15]  J. Biederman,et al.  Attention deficit/hyperactivity disorder across the lifespan. , 2002, Annual review of medicine.

[16]  V. Kusumakar,et al.  Glutamatergic changes with treatment in attention deficit hyperactivity disorder: a preliminary case series. , 2002, Journal of child and adolescent psychopharmacology.

[17]  J. McGough,et al.  Familial clustering of symptoms and disruptive behaviors in multiplex families with attention-deficit/hyperactivity disorder. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[18]  P. Asherson,et al.  Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children , 2000, Molecular Psychiatry.

[19]  K. Kendler,et al.  Replication of linkage studies of complex traits: an examination of variation in location estimates. , 1999, American journal of human genetics.

[20]  L. Rohde,et al.  ADHD in a school sample of Brazilian adolescents: a study of prevalence, comorbid conditions, and impairments. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[21]  Y. Chochi,et al.  Modulation of the Channel Activity of the ε2/ζ1-Subtype N-Methyl d-Aspartate Receptor by PSD-95* , 1999, The Journal of Biological Chemistry.

[22]  R. Gomez,et al.  DSM-IV AD/HD: confirmatory factor models, prevalence, and gender and age differences based on parent and teacher ratings of Australian primary school children. , 1999, Journal of child psychology and psychiatry, and allied disciplines.

[23]  R. Morris,et al.  Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein , 1998, Nature.

[24]  G. DuPaul,et al.  Peer tutoring for children with attention deficit hyperactivity disorder: effects on classroom behavior and academic performance. , 1998, Journal of applied behavior analysis.

[25]  C. Garner,et al.  SAP90 Binds and Clusters Kainate Receptors Causing Incomplete Desensitization , 1998, Neuron.

[26]  J D Terwilliger,et al.  Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set , 1998, Molecular Psychiatry.

[27]  B. Moghaddam,et al.  Regulation of striatal dopamine release by metabotropic glutamate receptors , 1998, Synapse.

[28]  E. Taylor,et al.  Attention-deficit hyperactivity disorder and hyperkinetic disorder , 1998, The Lancet.

[29]  D E Weeks,et al.  True and false positive peaks in genomewide scans: applications of length-biased sampling to linkage mapping. , 1997, American journal of human genetics.

[30]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[31]  N Risch,et al.  The Future of Genetic Studies of Complex Human Diseases , 1996, Science.

[32]  M. Wolraich,et al.  Comparison of diagnostic criteria for attention-deficit hyperactivity disorder in a county-wide sample. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[33]  R. Mark Wightman,et al.  Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter , 1996, Nature.

[34]  E. Lander,et al.  Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results , 1995, Nature Genetics.

[35]  D. Klein,et al.  Specificity in familial aggregation of phobic disorders. , 1995, Archives of general psychiatry.

[36]  M. Wolraich,et al.  Comparison of diagnostic criteria for attention deficit disorders in a German elementary school sample. , 1995, Journal of the American Academy of Child and Adolescent Psychiatry.

[37]  James C. Houk,et al.  Elements of the Intrinsic Organization and Information Processing in the Neostriatum , 1994 .

[38]  P. Wender,et al.  The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. , 1993, The American journal of psychiatry.

[39]  C. Kozak,et al.  Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on chromosome 2 , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  Phil A. Silva,et al.  DSM-III disorders in preadolescent children. Prevalence in a large sample from the general population. , 1987, Archives of general psychiatry.