Exploring <i>DRD4</i> and its interaction with <i>SLC6A3</i> as possible risk factors for adult ADHD: A meta‐analysis in four European populations

Sánchez-Mora, Cristina; Ribasés, Marta; Casas, Miquel; Bayés, Mònica; Bosch, Rosa; Fernàndez‐Castillo, Noèlia; Brunso, Lucas; Jacobsen, Kaya Kvarme; Landaas, Elisabeth Toverud; Lundervold, Astri J.; Groß-Lesch, Silke; Kreiker, Susanne; Jacob, Christian; Lesch, Klaus‐Peter; Buitelaar, Jan K.; Hoogman, Martine; Kiemeney, Lambertus A.; Kooij, J. J. Sandra; Mick, Eric; Asherson, Philip; Faraone, Stephen V.; Franke, Barbara; Reif, Andreas; Johansson, Stefan; Haavik, Jan; Ramos-Quiroga, Josep Antoni; Cormand, Bru

doi:10.1002/ajmg.b.31202

Cited by 22 publications

(20 citation statements)

References 83 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Here below we described candidate gene association studies (Table 1), 33, 34, 45, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65 pharmacogenetic (Table 2) 66, 67, 68 and biochemical (metabolomic) (Table 3) 46, 69, 70, 71, 72, 73, 74 studies for which it was possible to conduct meta-analysis. Moreover we described the studies for which the meta-analyses were not possible.…”

Section: Resultsmentioning

confidence: 99%

“…26, 28, 29, 76, 77 The current meta-analysis included six studies. 33, 53, 54, 57, 58, 60 Tovo-rodrigues et al 59 was excluded because insufficient data were reported. Also for this polymorphism different calculations were performed.…”

Section: Resultsmentioning

confidence: 99%

“…A summary of genetic studies of adult ADHD was reported in Franke et al 32 in a comprehensive review. The literature about adult ADHD now comprises six meta-analyses of candidate genes in International multi-center persistent ADHD collaboration (IMpACT) samples, 33, 34, 35, 36, 37, 38 two SNP-GWAS, 39, 40 two CNV-GWAS 41, 42 studies and three reviews of pharmacogenetics studies. 30, 43, 44 No meta-analyses of biochemical studies of adult ADHD have been reported.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies

2016

View full text Add to dashboard Cite

The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication ...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies

2016

View full text Add to dashboard Cite

show abstract

“…In the Indo-Caucasoid ADHD probands, we have also observed significant association of the higher repeats [5]. Another repeat variant rs4646984, located about 1.2 kb upstream of the initiation codon and affecting transcriptional activity of the promoter [14], showed nominal association of the duplicated allele in Caucasian population from Norway, Spain [55], and USA [14, 56]. On the other hand, haplotypes containing the single repeat allele have shown higher frequency in Caucasian ADHD probands from Hungary [13].…”

Section: Discussionmentioning

confidence: 96%

Catecholaminergic Gene Variants: Contribution in ADHD and Associated Comorbid Attributes in the Eastern Indian Probands

Ghosh

Sarkar²,

Bhaduri

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

Contribution of genes in attention deficit hyperactivity disorder (ADHD) has been explored in various populations, and several genes were speculated to contribute small but additive effects. We have assessed variants in four genes, DDC (rs3837091 and rs3735273), DRD2 (rs1800496, rs1801028, and rs1799732), DRD4 (rs4646984 and rs4646983), and COMT (rs165599 and rs740603) in Indian ADHD subjects with comorbid attributes. Cases were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV-TR after obtaining informed written consent. DNA isolated from peripheral blood leukocytes of ADHD probands (N = 170), their parents (N = 310), and ethnically matched controls (n = 180) was used for genotyping followed by population- and family-based analyses by the UNPHASED program. DRD4 sites showed significant difference in allelic frequencies by case-control analysis, while DDC and COMT exhibited bias in familial transmission (P < 0.05). rs3837091 “AGAG,” rs3735273 “A,” rs1799732 “C,” rs740603 “G,” rs165599 “G” and single repeat alleles of rs4646984/rs4646983 showed positive correlation with co-morbid characteristics (P < 0.05). Multi dimensionality reduction analysis of case-control data revealed significant interactive effects of all four genes (P < 0.001), while family-based data showed interaction between DDC and DRD2 (P = 0.04). This first study on these gene variants in Indo-Caucasoid ADHD probands and associated co-morbid conditions indicates altered dopaminergic neurotransmission in ADHD.

show abstract

“…The long version of the tandem duplication has been associated with attention deficit hyperactivity disorder (ADHD) and schizophrenia, conditions that are sometimes characterized by impulsivity [26], [30]; whereas, other studies have reported associations between the short allele and ADHD and/or high impulsivity [9], [31]. Two recent meta-analyses conclude that there is no association between the 120-bp tandem and ADHD [28], [32]. In the current study, there were no significant differences in self-reported impulsive sensation seeking (nor for impulsivity and sensation seeking measured separately) between the 120-bp duplication alleles.…”

Section: Discussionmentioning

confidence: 99%

Variants in the Dopamine-4-Receptor Gene Promoter Are Not Associated with Sensation Seeking in Skiers

et al. 2014

View full text Add to dashboard Cite

Sensation seeking is a personality trait that has been associated with disinhibited behaviours including substance use and gambling, but also with high-risk sport practices including skydiving, paragliding, and downhill skiing. Twin studies have shown that sensation seeking is moderately heritable, and candidate genes encoding components involved in dopaminergic transmission have been investigated as contributing to this type of behaviour. To determine whether variants in the regulatory regions of the dopamine-4-receptor gene (DRD4) influenced sport-specific sensation seeking, we analyzed five polymorphisms (−1106T/C, −906T/C, −809G/A, −291C/T, 120-bp duplication) in the promoter region of the gene in a cohort of skiers and snowboarders (n = 599) that represented a broad range of sensation seeking behaviours. We grouped subjects by genotype at each of the five loci and compared impulsive sensation seeking and domain-specific (skiing) sensation seeking between groups. There were no significant associations between genotype(s) and general or domain-specific sensation seeking in the skiers and snowboarders, suggesting that while DRD4 has previously been implicated in sensation seeking, the promoter variants investigated in this study do not contribute to sensation seeking in this athlete population.

show abstract

Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta‐analysis in four European populations

Cited by 22 publications

References 83 publications

Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies

Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies

Catecholaminergic Gene Variants: Contribution in ADHD and Associated Comorbid Attributes in the Eastern Indian Probands

Variants in the Dopamine-4-Receptor Gene Promoter Are Not Associated with Sensation Seeking in Skiers

Contact Info

Product

Resources

About