Genome‐wide association scan of attention deficit hyperactivity disorder

Neale, Benjamin M.; Lasky‐Su, Jessica; Anney, Richard; Franke, Barbara; Zhou, Kaixin; Maller, Julian; Vásquez, Alejandro Arias; Asherson, Philip; Chen, Wai; Banaschewski, Tobias; Buitelaar, Jan K.; Ebstein, Richard P.; Gill, Michael; Miranda, Ana; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A.; Steinhausen, Hans-Christoph; Sonuga‐Barke, Edmund; Mulas, Fernando; Taylor, Eric; Laird, Nan M.; Lange, Christoph; Daly, Mark J.; Faraone, Stephen V.

doi:10.1002/ajmg.b.30866

Cited by 229 publications

(219 citation statements)

References 37 publications

Supporting

Mentioning

212

Contrasting

Unclassified

Order By: Relevance

“…61 We also investigated evidence for association across the 72 replication SNPs using published GWAS results from the Psychiatric Genomics Consortium (https://pgc.unc.edu) for attention-deficit/hyperactivity disorder (ADHD), schizophrenia, bipolar disorder, and major depressive disorder. [63][64][65][66] …”

Section: Related Traitsmentioning

confidence: 99%

“…Twelve out of 14 variants previously reported to be associated with eating disorder-related symptoms, behaviors, and personality traits 59,60 were found in our discovery meta-analysis and 7 had the same direction of effect (P=0.774) (Table S10), with one SNP (inside RUFY1) having P<0.05 (binomial P=0.459). We did not find evidence for signal enrichment in the 60 independent SNPs found in the Psychiatric Genomics Consortium data for ADHD, schizophrenia, bipolar disorder, or major depressive disorder [63][64][65][66] (Table S11). …”

Section: Related Traitsmentioning

confidence: 99%

See 1 more Smart Citation

A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa

et al. 2010

View full text Add to dashboard Cite

Section: Related Traitsmentioning

confidence: 99%

Section: Related Traitsmentioning

confidence: 99%

A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa

et al. 2010

View full text Add to dashboard Cite

“…A recent genome-wide association study of ADHD performed by the International Multisite ADHD Genetics (IMAGE) group, which was conducted as a part of Genetic Association Information Network (GAIN), included 958 parent -child trios and 600 000 single-nucleotide polymorphisms (SNPs), but failed to provide convincing evidence for a number of common risk variants. 27 Although association analysis is a powerful tool to detect common variants with small effects, linkage analysis has proven successful in the detection of rare variants with large effects. Linkage, for common diseases, has been very successful in isolated populations, 28,29 as drift and founder effects lead to the extinction of most rare variants, while a small number is retained, which, over subsequent generations, become frequent.…”

Section: Introductionmentioning

confidence: 99%

Suggestive linkage of ADHD to chromosome 18q22 in a young genetically isolated Dutch population

et al. 2009

View full text Add to dashboard Cite

Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable, neuropsychiatric disorder among children. Linkage studies in isolated populations have proved powerful to detect variants for complex diseases, such as ADHD. We performed a genome-wide linkage scan for ADHD in nine patients from a genetically isolated population in the Netherlands, who were linked to each other within 10 generations through multiple lines of descent. The genome-wide scan was performed with a set of 400 microsatellite markers with an average spacing of ±10-12 cM. We performed multipoint parametric linkage analyses using both recessive and dominant models. Our genome scan pointed to several chromosomal regions that may harbour ADHD susceptibility genes. None exceeded the empirical genome-wide significance threshold, but the Log of odds (LOD) scores were 41.5 for regions 6p22 (Heterogenetic log of odds (HLOD) ¼ 1.67) and 18q21-22 (HLOD ¼ 2.13) under a recessive model. We followed up these two regions in a larger sample of ADHD patients (n ¼ 21, 9 initial and 12 extra patients). The LOD scores did not increase after increasing the sample size (6p22 (HLOD ¼ 1.51), 18q21-22 (HLOD ¼ 1.83)). However, the LOD score on 6p22 increased to 2 when a separate analysis was performed for the inattentive type ADHD children. The linkage region on chromosome 18q overlaps with the findings of association of rs2311120 (P ¼ 10 À5 ) and rs4149601 (P ¼ 10 À4 ) in the genome-wide association analysis for ADHD performed by the Genetic Association Information Network consortium. Furthermore, there was an excess of regions harbouring serotonin receptors (HTR1B, HTR1E, HTR4, HTR1D, and HTR6) that showed a LOD score 41 in our genome-wide scan.

show abstract

“…13,17 Since recently, genome-wide association studies (GWA) are becoming available for ADHD. [18][19][20] Eventually, they will lead to the identification of novel genes or pathways, as genome-wide studies do not rely on current biological knowledge. To date, eight genome-wide linkage analyses (GWLA) have been performed in ADHD.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide linkage analysis in a Dutch multigenerational family with attention deficit hyperactivity disorder

et al. 2009

View full text Add to dashboard Cite

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder. Genetics has an important role in the aetiology of this disease. In this study, we describe the clinical findings in a Dutch family with eight patients suffering from ADHD, in whom five had at least one other psychiatric disorder. We performed a genome-wide (parametric and nonparametric) affected-only linkage analysis. Two genomic regions on chromosomes 7 and 14 showed an excess of allele sharing among the definitely affected members of the family with suggestive LOD scores (2.1 and 2.08). Nonparametric linkage analyses (NPL) yielded a maxNPL of 2.92 (P¼0.001) for marker D7S502 and a maxNPL score of 2.56 (P¼0.003) for marker D14S275. We confirmed that all patients share the same haplotype in each region of 7p15.1-q31.33 and 14q11.2-q22.3. Interestingly, both loci have been reported before in Dutch (affected sib pairs) and German (extended families) ADHD linkage studies. Hopefully, the genome-wide association studies in ADHD will help to highlight specific polymorphisms and genes within the broad areas detected by our, as well as other, linkage studies. Keywords: attention deficit hyperactivity disorder; genome-wide linkage analysis INTRODUCTION Attention deficit hyperactivity disorder (ADHD) is a pervasive neuropsychiatric disorder affecting 4-5% of children and 0.5-2% of adults. 1 Genetics has an important role in the aetiology of the disorder. Data from clinical studies support the familial nature of ADHD. 2 Twin studies of categorically defined ADHD estimated heritability to be 60-90%. 3 Smalley 4 and Faraone et al 5 reported sibling relative-risk ratios (ls) of 4.0-8.0. Adoption studies report an increased frequency of ADHD in biological relatives of probands. 6-8 Smalley 4 proposed a genetic model for ADHD with an involvement of multiple genes with minor-to-moderate effect sizes interacting in an additive manner. Genome-wide exclusion mapping 9 and molecular studies of candidate genes 10 support this theory. However, the exact aetiology of ADHD is still unknown.The search for susceptibility genes involved in the development of ADHD has focused mostly on the dopaminergic system, largely because of the therapeutic effects of methylphenidate hydrochloride, which increases extracellular dopamine levels by inhibiting re-uptake from the synaptic cleft. Many association studies on genes such as the dopamine D4 receptor gene (DRD4), the dopamine D5 receptor gene (DRD5), dopamine beta hydroxylase (DBH), dopamine transporter (DAT1 or SLC6A3) and the synaptosomal-associated protein of 25 kDa (SNAP25) provide further support for the involvement of the dopaminergic pathway. [11][12][13]

show abstract

Genome‐wide association scan of attention deficit hyperactivity disorder

Cited by 229 publications

References 37 publications

A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa

A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa

Suggestive linkage of ADHD to chromosome 18q22 in a young genetically isolated Dutch population

Genome-wide linkage analysis in a Dutch multigenerational family with attention deficit hyperactivity disorder

Contact Info

Product

Resources

About