Institutional members access full text with Ovid®

Share this article on:

Sex-specific influence of DRD2 on ADHD-type temperament in a large population-based birth cohort

Nyman, Emma S.a,b; Loukola, Anua,c; Varilo, Teppoa,b,h; Taanila, Anjad,e; Hurtig, Tuulad,f; Moilanen, Irmaf; Loo, Sandrai; McGough, James J.i; Järvelin, Marjo-Riittad,g,k; Smalley, Susan L.i; Nelson, Stanley F.i,j; Peltonen, Leenaa,b,h,l

doi: 10.1097/YPG.0b013e32834c0cc8
Brief Reports

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a significant public-health impact. Previously, we described a candidate gene study in a population-based birth cohort that demonstrated an association with ADHD-affected males and the dopamine receptor D2 (DRD2). The current study evaluates potential associations of dopamine receptor genes and Cloninger temperament traits within this same sample. Participants with stringent lifetime ADHD diagnoses were ascertained systematically from the genetically isolated Northern Finland 1986 Birth Cohort (n=9432), resulting in 178 cases and 157 controls. Markers in all known dopamine receptor genes were genotyped. We report an association of DRD2 with low Persistence in females (rs1079727 P=0.02, rs1124491 P=0.02, rs1800497 P=0.03). The associated DRD2 minor allelic haplotype (CAA, P=0.03) is the same haplotype we previously associated with ADHD in males in this birth cohort. The current study further supports previous results on the role of DRD2 in individuals with ADHD. Investigations suggest that DRD2 may have an impact on both males and females, but the particular outcome appears sex-specific, manifesting as ADHD in males and low Persistence in females. Furthermore, these findings suggest that the putative role of low Persistence as an endophenotype for ADHD deserves further investigation.

aPublic Health Genomics Unit, Institute for Molecular Medicine Finland FIMM, University of Helsinki and National Institute for Health and Welfare

bDepartment of Medical Genetics, University of Helsinki

cDepartment of Public Health, Hjelt Institute, University of Helsinki

dInstitute of Health Sciences, University of Oulu

eUnit of General Practice, University Hospital of Oulu

fClinic of Child Psychiatry, University and University Hospital of Oulu

gDepartment of Child and Adolescent Health, National Public Health Institute, Finland

hProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts

iSemel Institute for Neuroscience and Human Behavior

jDepartment of Human Genetics, University of California, Los Angeles, California, USA

kDepartment of Epidemiology and Public Health, Imperial College London

lWellcome Trust Sanger Institute, Cambridge, UK

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.psychgenetics.com).

Correspondence to Emma S. Nyman, MSc, Institute for Molecular Medicine Finland FIMM, University of Helsinki and National Institute for Health and Welfare, Biomedicum Helsinki 2U, P.O. Box 212, FI-00251 Helsinki, Finland Tel: +358 (0)20 610 8475; fax: +358 (0)20 610 8480; e-mail: emma.nyman@thl.fi

Received September 3, 2011

Accepted August 12, 2011

© 2012 Lippincott Williams & Wilkins, Inc.