ADHD and DAT1: Further evidence of paternal over‐transmission of risk alleles and haplotype

Hawi, Ziarih; Kent, Lindsey; Hill, Matthew; Anney, Richard; Barry, Edwina; Franke, Barbara; Banaschewski, Tobias; Buitelaar, Jan K.; Ebstein, Richard P.; Miranda, Ana; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A.; Sonuga‐Barke, Edmund; Steinhausen, Hans Christoph; Faraone, Stephen V.; Asherson, Philip; Gill, Michael

doi:10.1002/ajmg.b.30960

Cited by 35 publications

(31 citation statements)

References 19 publications

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“…These authors reviewed 113 articles, including 3 genome-wide linkage studies, and association studies of 94 polymorphisms in 33 different candidate genes (p. 551). These authors and others (Hawi et al, 2010) describe ADHD as a highly heritable disorder. The authors categorized genetic associations according to those studies that effect the dopamine system, serotonin system, and the noradrenaline system.…”

Section: Characteristics Of Adhdmentioning

confidence: 95%

Traits of attention deficit/hyperactivity disorder in school-age children who stutter

Donaher¹,

Richels

2012

Journal of Fluency Disorders

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Section: Characteristics Of Adhdmentioning

confidence: 95%

Traits of attention deficit/hyperactivity disorder in school-age children who stutter

Donaher¹,

Richels

2012

Journal of Fluency Disorders

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“…Other studies have reported worse executive functioning among 10R homozygotes relative to 9R carriers (Loo et al, 2003; Stollstorff et al, 2010). The 10R allele also has a modest association with attention-deficit/hyperactivity disorder (Yang et al, 2007; Gizer et al, 2009; Hawi et al, 2010), a disorder involving impulsivity and impairment in executive function.…”

Section: Introductionmentioning

confidence: 99%

Indirect association of DAT1 genotype with executive function through white matter volume in orbitofrontal cortex

Chung

Ferrell

Clark

2015

Psychiatry Research: Neuroimaging

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The dopamine transporter (DAT1) gene has been associated with impulsivity and executive functioning. Further, DAT1 has been associated with brain structural characteristics and resting state connectivity. This study tested an indirect effect model in which DAT1 genotype (9-repeat carriers vs. 10-repeat homozygotes) is linked to phenotypes representing impulsivity and executive function (planning behavior) through effects on white matter (WM) volumes in prefrontal cortex (PFC), particularly orbitofrontal cortex (OFC). Adolescents (ages 14–18, n=38), were recruited from substance use treatment (n=22) and the community (n=16) to increase phenotype variation. Results indicated that DAT1 10/10 genotype was associated with lower WM volume in the PFC, specifically the left OFC. Further, lower WM volume in the left OFC predicted more difficulties in self-reported planning behavior, but not impulsivity. Indirect effect analysis indicated that lower WM volume in the left OFC mediated the association between DAT1 10/10 genotype and difficulties in planning behavior. Results suggest a brain structural mechanism, involving lower WM volume in the left OFC, as a link in the association between DAT1 genotype and a specific aspect of executive function. Genetic effects on regional WM volume that are linked to behavioral outcomes could ultimately inform the development of tailored interventions that address an individual’s unique risk factors.

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“…These genes have been reported to have paternal or maternal transmission or parent-of-origin effects in ADHD in previous studies. [6][7][8][9][10][11][12][13][14][15] In the cleaned SNP data, we did not find any SNPs in the DRD4 gene. Furthermore, we could not confirm the paternal or maternal transmission or parent-oforigin effects (p < 0.01) for HTR1B, SLC6A4, DRD4, DRD5 and FADS2.…”

Section: Discussionmentioning

confidence: 74%

“…7 In addition, we confirmed the paternal transmission (p = 0.022 for rs3863145) for DAT1 reported by Hawi and colleagues. 6,8 Based on QUANTO software, 39 we had greater than 80% power at α = 5% to detect maternal and paternal transmission for a sample size of 846 (trios), relative risk of 1.3, population risk of 0.1 and allele frequency of 20%.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a generalized parent-of-origin effect was observed in an Irish ADHD study. 6 Furthermore, gene-specific parent-of-origin effects have been observed for BDNF, 7 DAT1 (SLC6A3), 8 10 Several studies have failed to confirm an overall parent-of-origin effect; 10,15,16 however, gene-specific parent-of-origin effects cannot be excluded. 10 The conventional genome-wide association (GWA) study approach is a hypothesis-free, systematic search of tagging single nucleotide polymorphisms (SNPs) across the genome to identify novel associations with common diseases.…”

Section: Introductionmentioning

confidence: 99%

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Parent-of-origin effects of FAS and PDLIM1 in attention-deficit/hyperactivity disorder

Wang

Zhang

et al. 2012

jpn

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IntroductionAttention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable childhood-onset psychiatric disorder affecting 2%-6% of children worldwide and is characterized by developmentally inappropriate levels of inattention, hyperactivity and impulsivity. A previous review of genetic epidemiologic studies, including more than 14 published twin studies and 5 adoption studies, indicated that most of the variation was attributable to genetic factors, consistently demonstrating high heritability in the range of 75%-91%.1 Recent reviews further showed that twin studies of ADHD had been consistent with an average heritability rate of 76%. 2-5Previous studies have suggested that there may be a parentof-origin effect for ADHD candidate genes. For example, a generalized parent-of-origin effect was observed in an Irish ADHD study. 10 Several studies have failed to confirm an overall parent-of-origin effect; 10,15,16 however, gene-specific parent-of-origin effects cannot be excluded. 10The conventional genome-wide association (GWA) study approach is a hypothesis-free, systematic search of tagging single nucleotide polymorphisms (SNPs) across the genome to identify novel associations with common diseases. It has emerged as a powerful tool to identify disease-related genes for many common human disorders and other phenotypes. 17 Recently, several GWA studies of ADHD and related phenotypes were reported, and 4 of them were based on a sample set of the International Multicentre ADHD Genetics (IMAGE) study and genotyped with funds from the Genetic Association Information Network (GAIN).18 For example, the first GWA scan of ADHD was completed on a sample of 909 com plete proband-parent trios with a child with the combined subtype of ADHD from the IMAGE project.19 To Background: Previous studies have suggested that there may be a parent-of-origin effect for attention-deficit/hyperactivity disorder (ADHD) candidate genes. The objective of the present study was to investigate parent-of-origin effects using a genome-wide association analysis of the International Multicentre ADHD Genetics (IMAGE) study sample. Methods: Family-based association analysis for ADHD using 846 ADHD probands and their parents was performed using the PLINK program, and parent-of-origin effects were studied using a Z score for the difference in paternal versus maternal odds ratios. Results: We identified 44 single nucleotide polymorphisms (SNPs) showing parent-of-origin effects at a significance level of p < 0.001. The most significant SNP, rs7614907, is at position 3q13.33 in the CDGAP gene (p = 0.000064 for parent-of-origin effect). Furthermore, 2 genes (FAS and PDLIM1) showed moderate parent-of-origin effects (p = 0.00086 for rs9658691 and p = 0.00077 for rs11188249) and strong maternal transmission (p = 0.000059 for rs9658691 and p = 0.0000068 for rs11188249). In addition, ZNF775 showed a moderate parent-of-origin effect (p = 0.00036 for rs7790549) and strong paternal transmission (p = 0.000041 for rs7790549). Limitations: We only had 1 s...

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ADHD and DAT1: Further evidence of paternal over‐transmission of risk alleles and haplotype

Cited by 35 publications

References 19 publications

Traits of attention deficit/hyperactivity disorder in school-age children who stutter

Traits of attention deficit/hyperactivity disorder in school-age children who stutter

Indirect association of DAT1 genotype with executive function through white matter volume in orbitofrontal cortex

Parent-of-origin effects of FAS and PDLIM1 in attention-deficit/hyperactivity disorder

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