ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Ilott NE, 201021122117
Citation	Ilott N. E., Saudino K. J. and Asherson P. (2010) "Genetic influences on attention deficit hyperactivity disorder symptoms from age 2 to 3: a quantitative and molecular genetic investigation." BMC Psychiatry, 10: 102.
Study Design	twin study
Study Type	Candidate-gene association study
Sample Size	312 same-sex pairs of twins (144 MZ, 168 DZ; 164 male pairs, 148 female pairs)
Predominant Ethnicity	Caucasian
Population	USA
Gender	164 male pairs, 148 female pairs
Age Group	Children/Adolescents : 2-3 years

Detail Info

Summary	A tw in study design was used to assess the degree to which additive genetic variance influences ADHD symptom scores across two ages during infancy. A further objective in the study was to observe whether genetic association with a number of candidate markers reflects results from the quantitative genetic analysis. They have studied 312 twin pairs at two time-points, age 2 and age 3. A composite measure of ADHD symptoms from two parent-rating scales: The Child Behavior Checklist/1.5-5 years (CBCL) hyperactivity scale and the Revised Rutter Parent Scale for Preschool Children (RRPSPC) was used for both quantitative and molecular genetic analyses. At ages 2 and 3 ADHD symptoms are highly heritable (h² = 0.79 and 0.78, respectively) with a high level of genetic stability across these ages. However, they also observe a significant level of genetic change from age 2 to age 3. There are modest influences of non-shared environment at each age independently (e² = 0.22 and 0.21, respectively), with these influences being largely age-specific. In addition, they find modest association signals in DAT1 and NET1 at both ages, along with suggestive specific effects of 5-HTT and DRD4 at age 3. ADHD symptoms are heritable at ages 2 and 3. Additive genetic variance is largely shared across these ages, although there are significant new effects emerging at age 3. Results from this genetic association analysis reflect these levels of stability and change and, more generally, suggest a requirement for consideration of age-specific genotypic effects in future molecular studies.
Total Sample	The present analyses include 312 same-sex pairs of twins (144 MZ, 168 DZ; 164 male pairs, 148 female pairs). Although the sample was predominately Caucasian (85.4%), ethnicity was generally representative of the Massachusetts population (3.2% Black, 2% Asian, 7.3% Mixed, 2.2% Other). Socioeconomic status according to the Hollingshead Four Factor Index (1975) ranged from low to upper middle class (range = 20.5-66; M = 50.9, SD = 14.1).
Sample Collection	85.4% Caucasian, 3.2% Black, 2% Asian, 7.3% Mixed, 2.2% Other
Diagnosis Description	A composite measure of ADHD symptoms from two parent-rating scales: The Child Behavior Checklist/1.5 - 5 years (CBCL) hyperactivity scale and the Revised Rutter Parent Scale for Preschool Children (RRPSPC). Twins were selected preferentially for higher birth weight and gestational age. No twins with birth weights below 1750 grams or with gestational ages less than 34 weeks were included in the study. Twins were also excluded if one or both twins had a health problem that might affect motor activity (e.g., cerebral palsy, club foot) or had chromosomal abnormalities.
Technique	Residualised scores were used for all model fitting procedures. Both parents and offspring were genotyped. VNTR polymorphisms (DRD4 exon 3, DAT1 3' UTR, DAT1 intron 8, the 5-HTTLPR and MAOA promoter) were genotyped in-house. Single nucleotide polymorphisms (SNPs) were genotyped by Prevention.
Analysis Method	Tests of allelic association were performed using the Quantitative Transmission Disequilibrium Test (QTDT) on ADHD scores residualised for sex effects. Three models of association were tested using a likelihood ratio test implemented in QTDT: the 'Total Association' test (AT), the 'Within-Test' of association (AW) and the test of stratification (AP).
Result Description	At ages 2 and 3 ADHD symptoms are highly heritable with a high level of genetic stability across these ages. However, they also observe a significant level of genetic change from age 2 to age 3. There are modest influences of non-shared environment at each age independently, with these influences being largely age-specific. In addition, they find modest association signals in DAT1 and NET1 at both ages, along with suggestive specific effects of 5-HTT and DRD4 at age 3.

SNPs reported by this study (count: 15)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs6323			QTDT AW P-value=0.31, X²=1.03, df=1 at age 2; QTDT AW P-value=0.83, X²=0.97, df=1 at age 3	no significant association no significant association	Non-significant
rs6039806			QTDT AT P-value=0.96, X²=0, df=1, QTDT AW P-value=0.99, X²=0, df=1 at age 2; QTDT AT P-value=0.97, X²=0.08, df=1, QTDT AW P-value=0.52, X²=0.41, df=1 at age 3	no significant association no significant association	Non-significant
rs998424			QTDT AT P-value=0.07, X²=3.3, df=1, QTDT AW P-value=0.04, X²=4.42, df=1 at age 2; QTDT AT P-value=0.59, X²=0.83, df=1, QTDT AW P-value=0.07, X²=3.22, df=1 at age 3	modest, nominally significant associations in the AW test at...... modest, nominally significant associations in the AW test at age 2 More...	Significant
rs1051312			QTDT AT P-value=0.43, X²=0.63, df=1, QTDT AW P-value=0.85, X²=0.04, df=1 at age 2; QTDT AT P-value=0.58, X²=0, df=1, QTDT AW P-value=0.42, X²=0.65, df=1 at age 3	no significant association no significant association	Non-significant
rs11080121			QTDT AT P-value=0.14, X²=2.16, df=1, QTDT AW P-value=0.1, X²=2.71, df=1 at age 2; QTDT AT P-value=0.23, X²=0.12, df=1, QTDT AW P-value=0.03, X²=4.77, df=1 at age 3	modest, nominally significant associations in the AW test at...... modest, nominally significant associations in the AW test at age 3 More...	Significant
rs11564750			QTDT AT P-value=0.8, X²=0.06, df=1, QTDT AW P-value=0.39, X²=0.75, df=1 at age 2; QTDT AT P-value=0.43, X²=0.14, df=1, QTDT AW P-value=0.94, X²=0.01, df=1 at age 3	no significant association no significant association	Non-significant
rs11568324			QTDT AT P-value=0.04, X²=4.38, df=1, at age 2; QTDT AT P-value=0.13, X²=0.58, df=1, at age 3	modest, nominally significant associations in the AT test at...... modest, nominally significant associations in the AT test at age 2 More...	Significant
rs140701			QTDT AT P-value=0.09, X²=2.96, df=1, QTDT AW P-value=0.08, X²=3.03, df=1 at age 2; QTDT AT P-value=0.38, X²=0, df=1, QTDT AW P-value=0.07, X²=3.24, df=1 at age 3	modest, nominally significant associations in the AW test at...... modest, nominally significant associations in the AW test at age 3 More...	Non-significant
rs2020936			QTDT AT P-value=0.27, X²=1.24, df=1, QTDT AW P-value=0.17, X²=1.92, df=1 at age 2; QTDT AT P-value=0.4, X²=1.34, df=1, QTDT AW P-value=0.27, X²=1.2, df=1 at age 3	no significant association no significant association	Non-significant
rs2066713			QTDT AT P-value=0.84, X²=0.04, df=1, QTDT AW P-value=1, X²=0, df=11 at age 2; QTDT AT P-value=0.5, X²=1.27, df=1, QTDT AW P-value=0.57, X²=0.32, df=1 at age 3	no significant association no significant association	Non-significant
rs2242447			QTDT AT P-value=0.27, X²=1.23, df=1, QTDT AW P-value=0.31, X²=1.03, df=1 at age 2; QTDT AT P-value=0.18, X²=3.56, df=1, QTDT AW P-value=0.16, X²=2.01, df=1 at age 3	no significant association no significant association	Non-significant
rs2550946			QTDT AT P-value=0.51, X²=0.43, df=1, QTDT AW P-value=0.4, X²=0.71, df=1 at age 2; QTDT AT P-value=0.47, X²=0.16, df=1, QTDT AW P-value=0.32, X²=0.99, df=1 at age 3	no significant association no significant association	Non-significant
rs362987			QTDT AT P-value=0.84, X²=0.04, df=1, QTDT AW P-value=0.79, X²=0.07, df=1 at age 2; QTDT AT P-value=0.91, X²=0.04, df=1, QTDT AW P-value=0.39, X²=0.39, df=1 at age 3	no significant association no significant association	Non-significant
rs3746544			QTDT AT P-value=0.83, X²=0.05, df=1, QTDT AW P-value=0.67, X²=0.18, df=1 at age 2; QTDT AT P-value=0.21, X²=1.75, df=1, QTDT AW P-value=0.16, X²=1.98, df=1 at age 3	no significant association no significant association	Non-significant
rs3785157			QTDT AT P-value=0.06, X²=3.68, df=1, QTDT AW P-value=0.03, X²=4.65, df=1 at age 2; QTDT AT P-value=0.48, X²=0.37, df=1, QTDT AW P-value=0.04, X²=4.3, df=1 at age 3	modest, nominally significant associations in the AW test at...... modest, nominally significant associations in the AW test at ages 2 and 3 More...	Significant

Other variant reported by this study (count: 5)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
MAOA promoter VNTR			QTDT AW P-value=0.2, X²=4.68, df=3 at age 2; QTDT...... QTDT AW P-value=0.2, X²=4.68, df=3 at age 2; QTDT AW P-value=0.81, X²=0.05, df=3 at age 3 More...	no significant association	Non-significant
DRD4 exon3 VNTR			QTDT AT P-value=0.19, X²=4.74, df=3, QTDT AW P-va...... QTDT AT P-value=0.19, X²=4.74, df=3, QTDT AW P-value=0.35, X²=3.26, df=3 at age 2; QTDT AT P-value=0.05, X²=7.82, df=3, QTDT AW P-value=0.03, X²=8.69, df=3 at age 3 More...	modest, nominally significant associations in the AT and AW tests at age 3	Significant
5HTTLPR	short/long		QTDT AT P-value=0.57, X²=0.31, df=1, QTDT AW P-va...... QTDT AT P-value=0.57, X²=0.31, df=1, QTDT AW P-value=0.87, X²=0.03, df=1 at age 2; QTDT AT P value=0.87, X²=0.03, df=1, QTDT AW P-value=0.34, X²=0.91, df=1 at age 3 More...	no significant association	Non-significant
SLC6A3 3'-UTR VNTR			QTDT AT P-value=0.03, X²=7, df=2, QTDT AW P-value...... QTDT AT P-value=0.03, X²=7, df=2, QTDT AW P-value=0.08, X²=5.09, df=2 at age 2; QTDT AT P-value=0.004, X²=11.15, df=2, QTDT AW P-value=0.002, X²=12.17, df=2 at age 3 More...	modest, nominally significant associations in the AT test at age 2, and in the AT and AW tests at age 3, and still significant after bonferroni correction in the AW test at age 3	Significant
SLC6A3 intron8 VNTR			QTDT AT P-value=0.18, X²=3.42, df=2, QTDT AW P-va...... QTDT AT P-value=0.18, X²=3.42, df=2, QTDT AW P-value=0.24, X²=2.84, df=2 at age 2; QTDT AT P-value=0.24, X²=2.9, df=2, QTDT AW P-value=0.2, X²=3.21, df=2 at age 3 More...	no significant association	Non-significant

Genes reported by this study (count: 6)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SNAP25	no SNP showed modest, nominally significant association no SNP showed modest, nominally significant association	Non-significant
MAOA	no SNP showed modest, nominally significant association no SNP showed modest, nominally significant association	Non-significant
SLC6A3	1 SNP showed modest, nominally significant association in th...... 1 SNP showed modest, nominally significant association in the AT tests at ages 2 and 3 More...	Significant
SLC6A4	2 SNPs showed modest, nominally significant association in t...... 2 SNPs showed modest, nominally significant association in the AW tests at age 3 More...	Significant
SLC6A2	2 SNPs showed modest, nominally significant association in t...... 2 SNPs showed modest, nominally significant association in the AT and AW tests at age 2, and 1 SNP showed modest, nominally significant association in the AW tests at ages 2 and 3 More...	Significant
DRD4	1 SNP showed modest, nominally significant association in th...... 1 SNP showed modest, nominally significant association in the AT and AW tests at age 3 More...	Significant