American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics最新文献

{"title":"A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD.","authors":"Nanda N J Rommelse,&nbsp;Marieke E Altink,&nbsp;Alejandro Arias-Vásquez,&nbsp;Cathelijne J M Buschgens,&nbsp;Ellen Fliers,&nbsp;Stephen V Faraone,&nbsp;Jan K Buitelaar,&nbsp;Joseph A Sergeant,&nbsp;Barbara Franke,&nbsp;Jaap Oosterlaan","doi":"10.1002/ajmg.b.30848","DOIUrl":"https://doi.org/10.1002/ajmg.b.30848","url":null,"abstract":"<p><p>Meta-analyses indicate that the gene coding for the dopamine transporter (DAT1 or SLC6A3) is associated with an increased risk for ADHD. The mechanisms of this gene for ADHD are unclear. We systematically reviewed studies linking the VNTR in the 3' UTR of the DAT1 to neurophysiological and neuropsychological measures. In addition, a broad set of executive/cognitive and motor tests was administered to 350 children (5-11 years) and adolescents (11-19 years) with ADHD and 195 non-affected siblings. Two VNTRs (in intron 8 and the 3' UTR) and four SNPs (two 5' and two 3') in DAT1 were genotyped. The effect of the polymorphisms on neuropsychological functioning was studied. The review indicated that the majority of studies did not find a relation between DAT1 and neurophysiological or neuropsychological measures. In our sample, several of the polymorphisms of DAT1 were associated with ADHD and ADHD was associated with impaired neuropsychological functioning. However, none of the DAT1 polymorphisms was convincingly associated with neuropsychological dysfunctioning. This suggests that the effect of DAT1 on ADHD was not mediated by neuropsychological performance. However, since DAT1 is mainly expressed in the striatum and not the prefrontal cortex, it may influence striatum-related functions (such as delay aversion) more heavily than prefrontal related functions (such as executive functions). Associations of DAT1 with ADHD were only found in adolescents, which may suggest that DAT1 mainly exerts its effect in adolescence, and/or that having a more persistent form of ADHD may mark a more severe or homogeneous genetic form of the disorder.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1536-46"},"PeriodicalIF":2.8,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.b.30848","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27618484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attention deficit hyperactivity disorder in obese melanocortin-4-receptor (MC4R) deficient subjects: a newly described expression of MC4R deficiency.","authors":"Anat Agranat-Meged,&nbsp;Yoad Ghanadri,&nbsp;Iris Eisenberg,&nbsp;Ziva Ben Neriah,&nbsp;Eva Kieselstein-Gross,&nbsp;Stella Mitrani-Rosenbaum","doi":"10.1002/ajmg.b.30842","DOIUrl":"https://doi.org/10.1002/ajmg.b.30842","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is a heterogeneous highly heritable disorder which has recently been described to be comorbid in obese subjects. This study investigated phenotype/genotype associations in a consanguineous family with genetic obesity due to the melanocortin-4-receptor (MC4R) (C271R) mutation. MC4R deficiency disrupts hunger/satiety regulation resulting in abnormal eating behaviors. To date, the behavioral/psychiatric characteristics of MC4R deficiency have not been described except for a possible association with Binge Eating Disorder. Twenty-nine subjects of a family known to carry the MC4R (C271R) mutation, were genotyped for the mutation and underwent extensive evaluations in search for physical/psychiatric phenotype characteristics. Subjects originated from proband nuclear families with morbid obese children (BMI percentile > 97%). All probands were homozygous for the MC4R (C271R) mutation. ADHD prevalence was higher than expected only in the groups carrying the homozygous or heterozygous mutation (P = 0.00057, 0.0028, respectively). An obvious difference was observed between the homozygous group and the rest of the family in terms of obesity: homozygous subjects had childhood morbid obesity whereas heterozygous subjects included lean, normal weight and later onset obese subjects. A significant difference was found in ADHD prevalence between the homozygous MC4R (C271R) group (80%) and the rest of the family (22%) (P = 0.033) and a significant trend was found between ADHD prevalence and the number of MC4R (C271R) alleles (P = 0.0267). We conclude that in our sample, the MC4R (C271R) mutation causing obesity, is in association with ADHD. Identifying specific subgroups in which the comorbidity of obesity and ADHD occur may contribute to the understanding of the underlying molecular mechanisms.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1547-53"},"PeriodicalIF":2.8,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.b.30842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27662186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preliminary study of dopamine D4 receptor genotype and structural brain alterations in adults with ADHD.","authors":"Michael C Monuteaux,&nbsp;Larry J Seidman,&nbsp;Stephen V Faraone,&nbsp;Nikos Makris,&nbsp;Thomas Spencer,&nbsp;Eve Valera,&nbsp;Ariel Brown,&nbsp;George Bush,&nbsp;Alysa E Doyle,&nbsp;Samantha Hughes,&nbsp;Meghan Helliesen,&nbsp;Eric Mick,&nbsp;Joseph Biederman","doi":"10.1002/ajmg.b.30870","DOIUrl":"https://doi.org/10.1002/ajmg.b.30870","url":null,"abstract":"<p><p>An emerging literature has demonstrated an association between the dopamine D4 receptor (DRD4) gene and volumetric brain abnormalities in children with ADHD. However, these results have not been extended to adults and have not addressed the impact of comorbidity. Our objective was to examine the DRD4 7R gene and volumetric brain abnormalities in adults with ADHD while accounting for comorbidity with bipolar disorder (BPD). Subjects were male and female adult outpatient referrals stratified into two diagnostic groups: 24 with ADHD, 19 with ADHD and BPD, as well as 20 male and female adult community controls without ADHD or BPD. We measured volumes (cm(3)) of a priori selected brain regions (superior frontal, middle frontal, anterior cingulate, and cerebellum cortices) by structural magnetic resonance imaging. Among adults with ADHD, subjects with the 7-repeat allele of the DRD4 gene had a significantly smaller mean volume in the superior frontal cortex and cerebellum cortex compared to subjects without this allele. In contrast, no such effects were detected in the adults with ADHD + BPD or controls. Our findings suggest that volumetric abnormalities in the dorsolateral prefrontal cortex and cerebellum may represent an intermediate neuroanatomical phenotype between DRD4 genotype and the clinical expression of ADHD in adults, but only in ADHD subjects without comorbid BPD. These result support the heterogeneity of ADHD and provides insights as to its underlying pathophysiology.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1436-41"},"PeriodicalIF":2.8,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.b.30870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27818757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs.","authors":"S Johansson,&nbsp;H Halleland,&nbsp;A Halmøy,&nbsp;K K Jacobsen,&nbsp;E T Landaas,&nbsp;M Dramsdahl,&nbsp;O B Fasmer,&nbsp;P Bergsholm,&nbsp;A J Lundervold,&nbsp;C Gillberg,&nbsp;K Hugdahl,&nbsp;P M Knappskog,&nbsp;J Haavik","doi":"10.1002/ajmg.b.30662","DOIUrl":"https://doi.org/10.1002/ajmg.b.30662","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable psychiatric disorder in children and adults. Recent meta-analyses have indicated an association between genes involved in dopaminergic signaling and childhood ADHD, but little is known about their possible role in adult ADHD. In this study of adults with ADHD, we evaluated the three most commonly studied ADHD candidate genetic polymorphisms; the dopamine receptor D4 (DRD4) exon 3 VNTR repeat, a microsatellite repeat 18.5 kb upstream of the DRD5 locus and the 3'UTR dopamine transporter SLC6A3 (DAT 1) VNTR. We examined 358 clinically diagnosed adult Norwegian ADHD patients (51% males) and 340 ethnically matched controls. We found a nominally significant overall association with adult ADHD for the DRD5 microsatellite marker (P = 0.04), and a trend toward increased risk associated with the 148-bp allele consistent with recent meta-analyses. The strongest overall association (P = 0.02) and increased risk for the 148-bp allele [odds ratio (OR) = 1.27 (95% CI: 1.00-1.61)] were seen in the inattentive and combined inattentive/hyperactive group as previously reported for childhood ADHD. No association was found for the DRD4 or SLC6A3 polymorphisms in this patient sample. In conclusion, our results among adults with a clinical diagnosis of ADHD support an association between ADHD and the DRD5 locus, but not the DRD4 or SLC6A3 loci. It is possible that the latter polymorphisms are associated with a transient form of ADHD with better long-term clinical outcome.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1470-5"},"PeriodicalIF":2.8,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.b.30662","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27119268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential association between MAOA, ADHD and neuropsychological functioning in boys and girls.","authors":"Nanda N J Rommelse,&nbsp;Marieke E Altink,&nbsp;Alejandro Arias-Vásquez,&nbsp;Cathelijne J M Buschgens,&nbsp;Ellen Fliers,&nbsp;Stephen V Faraone,&nbsp;Jan K Buitelaar,&nbsp;Joseph A Sergeant,&nbsp;Jaap Oosterlaan,&nbsp;Barbara Franke","doi":"10.1002/ajmg.b.30845","DOIUrl":"https://doi.org/10.1002/ajmg.b.30845","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) is more common in boys than in girls. It has been hypothesized that this sex difference might be related to genes on the X-chromosome, like Monoamine Oxidase A (MAOA). Almost all studies on the role of MAOA in ADHD have focused predominantly on boys, making it unknown whether MAOA also has an effect on ADHD in girls, and few studies have investigated the relationship between MAOA and neuropsychological functioning, yet this may provide insight into the pathways leading from genotype to phenotype. The current study set out to examine the relationship between MAOA, ADHD, and neuropsychological functioning in both boys (265 boys with ADHD and 89 male non-affected siblings) and girls (85 girls with ADHD and 106 female non-affected siblings). A haplotype was used based on three single nucleotide polymorphisms (SNPs) (rs12843268, rs3027400, and rs1137070). Two haplotypes (GGC and ATT) captured 97% of the genetic variance in the investigated MAOA SNPs. The ATT haplotype was more common in non-affected siblings (P = 0.025), conferring a protective effect for ADHD in both boys and girls. The target and direction of the MAOA effect on neuropsychological functioning was different in boys and girls: The ATT haplotype was associated with poorer motor control in boys (P = 0.002), but with better visuo-spatial working memory in girls (P = 0.01). These findings suggest that the genetic and neuropsychological mechanisms underlying ADHD may be different in boys and girls and underline the importance of taking into account sex effects when studying ADHD.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1524-30"},"PeriodicalIF":2.8,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.b.30845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27616867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replication of a rare protective allele in the noradrenaline transporter gene and ADHD.","authors":"X Xu, Z Hawi, K J Brookes, R Anney, M Bellgrove, B Franke, E Barry, W Chen, J Kuntsi, T Banaschewski, J Buitelaar, R Ebstein, M Fitzgerald, A Miranda, R D Oades, H Roeyers, A Rothenberger, J Sergeant, E Sonuga-Barke, H-C Steinhausen, S V Faraone, M Gill, P Asherson","doi":"10.1002/ajmg.b.30872","DOIUrl":"10.1002/ajmg.b.30872","url":null,"abstract":"<p><p>Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polymorphisms (SNPs) within the norepinephrine transporter (SLC6A2) gene were found to be associated with attention deficit hyperactivity disorder (ADHD). The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the US. Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 and rs3785143 in SLC6A2. Significant association of the two markers was not observed in the two independent replication samples. However, across all four datasets the overall evidence of association with ADHD was significant (for SNP rs11568324 P = 0.0001; average odds ratio = 0.33; for SNP rs3785143 P = 0.008; average odds ratio = 1.3). The data were consistent for rs11568324, suggesting the existence of a rare allele conferring protection for ADHD within the SLC6A2 gene. Further investigations should focus on identifying the mechanisms underlying the protective effect.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1564-7"},"PeriodicalIF":0.0,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587507/pdf/nihms76284.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27806421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.","authors":"Tania DasBanerjee, Frank A Middleton, David F Berger, John P Lombardo, Terje Sagvolden, Stephen V Faraone","doi":"10.1002/ajmg.b.30877","DOIUrl":"10.1002/ajmg.b.30877","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the spontaneously hypertensive rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar/Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal days (PNDs) 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real-time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11, and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc, and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1, and Hes6. The epigenetic genes Crebbp, Mecp2, and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1554-63"},"PeriodicalIF":0.0,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587509/pdf/nihms76111.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27805843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study.","authors":"Joseph Biederman, Jang Woo Kim, Alysa E Doyle, Eric Mick, Jesen Fagerness, Jordan W Smoller, Stephen V Faraone","doi":"10.1002/ajmg.b.30874","DOIUrl":"10.1002/ajmg.b.30874","url":null,"abstract":"<p><p>A growing body of literature finds gender differences in ADHD. However, little is known about the causes of these differences. One possibility is that ADHD risk genes have sexually dimorphic effects. We have investigated four ADHD candidate genes (COMT, SLC6A2, MAOA, SLC6A4) for which there is evidence of sexually dimorphic effects. Past neurobiological and genetic studies suggest that COMT, and SLC6A4 variants may have a greater influence on males and that SLC6A2, and MAOA variants may have a greater influence on females. Our results indicate that genetic associations are stronger when stratified by sex and in the same direction as the previous neurobiological studies indicate: associations were stronger in males for COMT, SLC6A4 and stronger in females for SLC6A2, MAOA. Moreover, we found a statistically significant gender effect in the case of COMT (P = 0.007) when we pooled our work with a prior study. In conclusion, we have found some evidence suggesting that the genetic association for these genes with ADHD may be influenced by the sex of the affected individual. Although our results are not fully validated yet, they should motivate further investigation of gender effects in ADHD genetic association studies.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1511-8"},"PeriodicalIF":0.0,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587524/pdf/nihms76081.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27805842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of association of the dopamine transporter gene in a French ADHD sample.","authors":"M Wohl,&nbsp;C Boni,&nbsp;M Asch,&nbsp;S Cortese,&nbsp;S Orejarena,&nbsp;M C Mouren,&nbsp;P Gorwood,&nbsp;D Purper-Ouakil","doi":"10.1002/ajmg.b.30695","DOIUrl":"https://doi.org/10.1002/ajmg.b.30695","url":null,"abstract":"<p><p>Discrepancies in the role of the 40 bp VNTR polymorphism of the dopamine transporter gene (DAT1) in attention-deficit hyperactivity disorder (ADHD) could be due to various sources of genetic or phenotypical heterogeneity. We therefore analyzed a sample of 146 ADHD children and their parents, with a transmission disequilibrium test (TDT) design, assessing age, inattention, and hyperactivity dimensions and total score of the ADHD Rating Scale, the number of errors and the total score at Stroop Color-Word test, and the total score at the Trail Making Test. The TDT for 10-repeat (10-R) allele shows a perfect lack of transmission bias (Mc Nemar chi(2) = 0) and PBAT analyses showed no role of this polymorphism for any of the studied endophenotypes. Lack of statistical power is always a possibility, but with a sample size above the average of the majority of previous studies, and an odds ratio (number of transmitted versus untransmitted 10-R allele) of 1.00 exactly, this possibility may be considered as not very likely.</p>","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1509-10"},"PeriodicalIF":2.8,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.b.30695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40505266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the dopamine transporter gene and ADHD symptoms in a Canadian population-based sample of same-age twins.","authors":"Isabelle Ouellet-Morin,&nbsp;Karen G Wigg,&nbsp;Yu Feng,&nbsp;Ginette Dionne,&nbsp;Philippe Robaey,&nbsp;Mara Brendgen,&nbsp;Frank Vitaro,&nbsp;Louise Simard,&nbsp;Russell Schachar,&nbsp;Richard E Tremblay,&nbsp;Daniel Pérusse,&nbsp;Michel Boivin,&nbsp;Cathy L Barr","doi":"10.1002/ajmg.b.30677","DOIUrl":"https://doi.org/10.1002/ajmg.b.30677","url":null,"abstract":"Attention deficit hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder emerging during childhood. Psychostimulant medications (e.g., methylphenidate) noticeably reduce ADHD symptoms in most children. Since methylphenidate inhibits dopamine transporter activity, the dopamine transporter gene (DAT1) was considered to be the prime candidate risk gene in ADHD. Several studies found evidence for an association between the 10‐repeat allele of the variable number of tandem repeat (VNTR) located in the 3′ untranslated region and ADHD and/or ADHD symptoms in clinical and population‐based samples. However, this finding was not replicated in all samples. In this study, we investigated the association between the DAT1 gene and ADHD symptoms in a population‐based twin sample from Québec (Canada). We used two polymorphisms, the VNTR and rs27072, the last providing the most significant results in a clinical sample from Toronto (Ontario, Canada). No association was noted between the VNTR and ADHD symptoms in children at 6 and 7 years of age, as reported by teachers. However, a significant association was found for the rs27072 polymorphism and symptoms of inattention and hyperactivity/impulsivity. These findings indicate that the DAT1 gene contributes to ADHD symptoms in this sample and further suggest that the VNTR may not be the optimal polymorphism for study in all populations. © 2007 Wiley‐Liss, Inc.","PeriodicalId":520553,"journal":{"name":"American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics","volume":" ","pages":"1442-9"},"PeriodicalIF":2.8,"publicationDate":"2008-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ajmg.b.30677","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27198310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}