Hyperactivity and Spelling Disability: Testing for Shared Genetic Aetiology

Stevenson, Jim; Pennington, Bruce F.; Gilger, Jeffrey W.; DeFries, John C.; Gillis, Jacquelyn J.

doi:10.1111/j.1469-7610.1993.tb01779.x

Cited by 142 publications

(107 citation statements)

References 34 publications

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“…Additional lines of evidence from twin, adoption, and segregation analysis studies suggest that the familial aggregation of ADHD has a substantial genetic component. Twin studies find greater similarity for ADHD and components of the syndrome between monozygotic twins compared with dizygotic twins [Lopez, 1965;Goodman and Stevenson, 1989;Gillis et al, 1992;Stevenson et al, 1993;Waldeman et al, 1994;Gjone et al, 1996]. Their results suggest that the heritability of ADHD ranges from .88 to 1.0, suggesting a substantial role for genetic factors in its etiology.…”

Section: Introductionmentioning

confidence: 82%

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness

et al. 1998

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Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families.

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Section: Introductionmentioning

confidence: 82%

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness

et al. 1998

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“…18 ADHD has been considered a complex genetic trait based upon the absence of a clearcut line to define the affection-status phenotype and also because its high comorbidity with other disorders strongly suggest the effect of complex epistatic or pleiotropic effects acting in common with the environment, which means that the same gene or genes is or are associated with different and concurrent phenotypes. 88 Furthermore, ADHD is highly related to oppositional disorder (35%) in childhood, with conduct disorder (50%), alcohol and substance abuse during adolescence and with antisocial personality disorder (15%), alcoholism (25%), and substance dependence (20%) during early adulthood. 4,[89][90][91][92][93][94][95][96][97] Based upon complex segregation analyses [4][5][6] and high estimated heritability values [1][2][3] that strongly suggest the presence of a major gene underlying the ADHD susceptibility, we considered the possibility of a genetic mapping of this major factor by analyzing multigenerational and extended pedigrees coming from a genetic isolate.…”

Section: Discussionmentioning

confidence: 99%

Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate

et al. 2004

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Association/linkage between dopamine D4 receptor (DRD4) polymorphisms and attentiondeficit/hyperactivity disorder (ADHD) has been suggested by case-control-and nuclear-familybased studies. Here, we present a candidate gene analysis for DRD4 using 14 extended and multigenerational families segregating ADHD derived from the 'Paisa' community of Antioquia, Colombia, a genetic isolate. Two DRD4 polymorphisms (a 120 bp tandem duplication at the promoter and a 48 bp-VNTR at exon 3), reported associated to ADHD, were genotyped. Parametric and non-parametric linkage analyses, and a family-based association test (FBAT), the pedigree disequilibrium test (PDT), were applied to search for evidence of association/ linkage. Two-point LOD scores were significantly negative, with values ranging from À3.21 (P ¼ 0.011158) to À7.66 (P ¼ 0.000091 at h ¼ 0). Non-parametrical analysis resulted in nonsignificant evidence for linkage. The PDT showed a moderate trend toward significance of association/linkage between the 7-repeat (7R) allele at the 48 bp VNTR and ADHD (P ¼ 0.0578). Furthermore, the haplotype analysis shows a significant association/linkage of the 7R-240 bp haplotype (P ¼ 0.0467) with ADHD. Results suggest that either a moderate DRD4 genetic effect, or linkage disequilibrium of DRD4 with an ADHD disease locus in the vicinity or the linkage to a phenotypic component of the ADHD spectrum could be underlying this association/linkage. These results provide further evidence for the association of ADHD to genetic variation in or near to DRD4 and replicate the previously reported association between ADHD and the 7R allele.

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“…Thus, the same gene or genes may be associated with different and concurrent phenotypes. 5,6 Comorbidity of ADHD has been shown with depression, anxiety, oppositional disorder in childhood, conduct disorder, alcohol and substance abuse during adolescence, antisocial personality disorder, alcoholism, and substance dependence during early adulthood. [7][8][9][10][11] Biological causes have been strongly implicated in the etiology of ADHD: (1) this disorder has been shown to follow Mendelian patterns in some families that have been used for linkage and segregation studies [12][13][14][15] ; (2) brain abnormalities that have been noted in magnetic resonance imaging (MRI) studies, single photon emission computed tomography (Table 2); and (3) neurophysiological studies (heart rate deceleration, electroencephalogram amplitude of response to stimulation, and habituation on evoked responses of ADHD patients).…”

Section: Attention-deficit/hyeractivity Disorder (Adhd): Overviewmentioning

confidence: 99%

Attention deficit/hyperactivity disorder (ADHD): Complex phenotype, simple genotype?

Acosta

Arcos‐Burgos

Muenke

2004

Genetics in Medicine

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Complex genetic traits refer to those phenotypes not fitting patterns of Mendelian segregation and/or assortment but exhibiting a preferential familial clustering that cannot be explained by cultural or environmental causes.Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood and probably the most controversial. ADHD has been considered a complex genetic trait based upon the absence of a clear-cut boundary between affected and unaffected status. Furthermore, its high comorbidity with other disorders strongly suggests complex epistatic or pleiotropic effects acting in common with the environmental influences. This implies that the same gene or genes is or are associated with different and concurrently occurring phenotypes. In this study, we will review clinical and epidemiological aspects related to the ADHD phenotype, which are considered either as categorical or continuous traits. We also will discuss genetic models underlying the complexity of this behavioral phenotype and the probable role of epistatic interactions between major genes contributing to the ADHD phenotype. Genet Med 2004:6(1):1-15.

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Hyperactivity and Spelling Disability: Testing for Shared Genetic Aetiology

Cited by 142 publications

References 34 publications

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness

Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate

Attention deficit/hyperactivity disorder (ADHD): Complex phenotype, simple genotype?

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