Refining the attention deficit hyperactivity disorder phenotype for molecular genetic studies

Abstract

It is well established that attention deficit hyperactivity disorder (ADHD) is a familial and highly heritable disorder. Consequently, much effort is being directed towards searching for specific susceptibility genes. There is a growing trend, across the field of complex disease genetics, towards undertaking secondary analyses based on refined phenotypic definitions and in testing whether specific susceptibility genes modify the phenotypic presentation of the disorder in question. It is crucial that good, empirically derived arguments are made before undertaking multiple analyses on different phenotype refinements. In this review article, we consider the evidence from genetic epidemiological studies as well as key clinical studies that provide guidance on examining the ADHD phenotype for the purpose of molecular genetic studies. Specifically, findings on categorical versus dimensional conceptualisations of ADHD, reporter effects, comorbidity, ADHD subtypes and persistence are reviewed. Current evidence suggests that for the purpose of identifying susceptibility genes for ADHD, parent and teachers should be used as informants and that focusing on the clinical diagnosis of ADHD is useful. There is also good empirical support in favour of examining antisocial behaviour in ADHD. Genetic studies of dimensional ADHD are useful for other complementary purposes.

Phenotypic and measurement influences on heritability estimates in childhood ADHD

“…The combined ADHD ? CD subtype has been suggested as a more strongly genetically determined subtype than ADHD alone [108], however, cross-sectional as well as longitudinal twin studies also suggested additional environmental as well as specific genetic risk factors for CD. Therefore, well-known environmental risk factors should be accounted for during analysis.…”

Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype

“…It has been suggested that this approach may be an important complement to the categorical diagnosis in molecular genetic studies. [35][36][37] To maintain consistency among studies, tag SNPs selected by the International Multi-centre ADHD Gene (IMAGE) project, excluding those with a minor allele frequency ≤ 0.02, were genotyped. 30 In addition, 2 tag SNPs (rs15534, rs7188230) were selected to extend the 3′ flanking region examined.…”

Diversidade de resultados no estudo do transtorno de déficit de atenção e hiperatividade

“…A esse conjunto de características acresce a elevada incidência de transtornos comórbidos (American Psychiatric Association, 1994Thapar, Langley, O'Donovan & Owen, 2006). Dados recentes estimam uma prevalência mundial na ordem dos 5,2%, maior no sexo masculino do que no feminino (Polanczyk, de Lima, Horta, Biederman & Rohde, 2007).…”