COMTandDAT1genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect.
Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population.



We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes.



Linear regression analyses demonstrated that the increasing number ofCOMT158Val andDAT110R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049,t= 2.189,p= 0.029,R2= 0.012, and β coefficient = 0.064,t= 2.832,p= 0.005,R2= 0.008, respectively). The presence of bothCOMT158Val andDAT110R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ2= 4.561,p= 0.033, odds ratio 2.473, 95% confidence interval 1.048-5.838) from this cohort. We did not observe these associations in girls.



Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated.



This study demonstrates a role forCOMTandDAT1genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism onCOMTandDAT1gene expression.
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Glaucia C
GC
Akutagava-Martins
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Angelica
A
Salatino-Oliveira
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Christian
C
Kieling
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Julia P
JP
Genro
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Guilherme V
GV
Polanczyk
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Luciana
L
Anselmi
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Ana M B
AM
Menezes
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Helen
H
Gonçalves
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Fernando C
FC
Wehrmeister
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Fernando C
FC
Barros
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Sidia M
SM
Callegari-Jacques
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Luis A
LA
Rohde
From the Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Akutagava-Martins, Salatino-Oliveira, Genro, Hutz); the Child and Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil (Kieling, Rohde); the Department of Psychiatry, Universidade de São Paulo, São Paulo, São Paulo, Brazil (Polanczyk); the Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Anselmi, Menezes, Gonçalves, Wehrmeister, Barros); the Graduate Program in Health and Behavior, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil (Barros); the Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (Callegari-Jacques); and the Institute for Developmental Psychiatry for Children and Adolescents (INCT-CNPq), Brazil (Polanczyk, Rohde).
Mara H
MH
Hutz
D000293:Adolescent; D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D016014:Linear Models; D008297:Male; D010641:Phenotype; D015995:Prevalence; D011569:Psychiatric Status Rating Scales; D012727:Sex Characteristics; D011795:Surveys and Questionnaires
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase