Relations between multi-informant assessments of ADHD symptoms, DAT1, and DRD4.
Researchers conducting candidate gene studies of attention-deficit/hyperactivity disorder (ADHD) typically obtain symptom ratings from multiple informants (i.e., mothers, fathers, and teachers) and use a psychologist's best estimate or a simple algorithm, such as taking the highest symptom ratings across informants, to construct diagnostic phenotypes for estimating association. Nonetheless, these methods have never been empirically validated in the context of a molecular genetic study. In the current study, the authors systematically evaluated several methods of operationalizing phenotypes and the resulting evidence for association between ADHD and the candidate genes: dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4). Use of symptom scores as continuous scales in regression analysis suggested that the combination of mother and teacher ratings yielded the strongest evidence for association between hyperactive-impulsive ADHD symptoms and DAT1 and between inattentive ADHD symptoms and DRD4. Teacher ratings alone were sufficient for evaluating the association between inattentive symptoms and DAT1. Further, this regression-based method consistently yielded stronger evidence for association among ADHD symptoms, DAT1, and DRD4 than did three simple algorithms (i.e., the and, or, and averaging rules). The implications of these results for future molecular genetic studies of ADHD are discussed.
Gizer
Ian R
IR
Department of Psychology, Emory University, 532 N. Kilgo Circle, Atlanta, GA 30322, USA. igizer@emory.edu
Waldman
Irwin D
ID
Abramowitz
Ann
A
Barr
Cathy L
CL
Feng
Yu
Y
Wigg
Karen G
KG
Misener
Virginia L
VL
Rowe
David C
DC
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D015588:Observer Variation; D010552:Personality Assessment / Q000706:statistics & numerical data*; D011594:Psychometrics / Q000706:statistics & numerical data; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D015203:Reproducibility of Results; D012931:Social Environment; D013223:Statistics as Topic
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4