A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy.
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood behavioral disorder. Identifying risk factors for ADHD may lead to improved intervention and prevention. The dopamine transporter gene (DAT1) is associated with ADHD in several studies, with an average 1.2 odds ratio and evidence of heterogeneity across data sets.


OBJECTIVE
To investigate sources of heterogeneity by refining the DAT1 association using additional markers and investigating gene-environment interaction between DAT1 and maternal use of alcohol and tobacco during pregnancy.


METHODS
Prospective study.


METHODS
Children with ADHD from child behavior clinics in the southeast of England and in the Taipei area of Taiwan.


METHODS
Within-family tests of association using 2 repeat polymorphisms in the 3' untranslated region and intron 8 plus additional markers in the English sample.


METHODS
Transmission ratios of risk alleles from heterozygote parents to affected offspring and comparison of the transmission ratios in high- and low-exposure groups for the environmental variables.


RESULTS
A novel association was identified between ADHD, the intron 8 polymorphism, and a specific risk haplotype in both English and Taiwanese samples. The risk haplotype showed significant interactions with maternal use of alcohol during pregnancy.


CONCLUSIONS
The identification of a common haplotype in 2 independent populations is an important step toward identifying functionally significant regions of DAT1. Interaction between DAT1 genotypes and maternal use of alcohol during pregnancy suggests that DAT1 moderates the environmental risk and has implications for the prevention of ADHD. Further studies are required to delineate the precise causal risk factor involved in this interaction.
Brookes
Keeley-Joanne
KJ
Medical Research Council Social Genetic Developmental Psychiatry Centre, Institute of Psychiatry, London, England.
Mill
Jon
J
Guindalini
Camilla
C
Curran
Sarah
S
Xu
Xiaohui
X
Knight
Jo
J
Chen
Chih-Ken
CK
Huang
Yu-Shu
YS
Sethna
Vaheshta
V
Taylor
Eric
E
Chen
Wai
W
Breen
Gerome
G
Asherson
Philip
P
D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology* / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002874:Chromosome Mapping; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004739:England / Q000453:epidemiology; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D018811:Maternal Exposure / Q000009:adverse effects; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013624:Taiwan / Q000453:epidemiology; D044465:White People / Q000235:genetics
D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D000431:Ethanol