A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts

Middeldorp, Christel M., Hammerschlag, Anke R., Ouwens, Klaasjan G., Groen-Blokhuis, Maria M., St Pourcain, Beate, Greven, Corina U., Pappa, Irene, Tiesler, Carla M. T., Ang, Wei, Nolte, Ilja M., Vilor-Tejedor, Natalia, Bacelis, Jonas, Ebejer, Jane L., Zhao, Huiying, Davies, Gareth E., Ehli, Erik A., Evans, David M., Fedko, Iryna O., Guxens, Monica, Hottenga, Jouke-Jan, Hudziak, James J., Jugessur, Astanand, Kemp, John P., Krapohl, Eva, Martin, Nicholas G., Murcia, Mario, Myhre, Ronny, Ormel, Johan, Ring, Susan M., Standl, Marie, Stergiakouli, Evie, Stoltenberg, Camilla, Thiering, Elisabeth, Timpson, Nicholas J., Trzaskowski, Maciej, van der Most, Peter J., Wang, Carol, Nyholt, Dale R., Medland, Sarah E., Neale, Benjamin, Jacobsson, Bo, Sunyer, Jordi, Hartman, Catharina A., Whitehouse, Andrew J. O., Pennell, Craig E., Heinrich, Joachim, Plomin, Robert, Smith, George Davey, Tiemeier, Henning, Posthuma, Danielle and Boomsma, Dorret I. (2016) A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts. Journal of the American Academy of Child and Adolescent Psychiatry, 55 10: 896-905.e6. doi:10.1016/j.jaac.2016.05.025


Author Middeldorp, Christel M.
Hammerschlag, Anke R.
Ouwens, Klaasjan G.
Groen-Blokhuis, Maria M.
St Pourcain, Beate
Greven, Corina U.
Pappa, Irene
Tiesler, Carla M. T.
Ang, Wei
Nolte, Ilja M.
Vilor-Tejedor, Natalia
Bacelis, Jonas
Ebejer, Jane L.
Zhao, Huiying
Davies, Gareth E.
Ehli, Erik A.
Evans, David M.
Fedko, Iryna O.
Guxens, Monica
Hottenga, Jouke-Jan
Hudziak, James J.
Jugessur, Astanand
Kemp, John P.
Krapohl, Eva
Martin, Nicholas G.
Murcia, Mario
Myhre, Ronny
Ormel, Johan
Ring, Susan M.
Standl, Marie
Stergiakouli, Evie
Stoltenberg, Camilla
Thiering, Elisabeth
Timpson, Nicholas J.
Trzaskowski, Maciej
van der Most, Peter J.
Wang, Carol
Nyholt, Dale R.
Medland, Sarah E.
Neale, Benjamin
Jacobsson, Bo
Sunyer, Jordi
Hartman, Catharina A.
Whitehouse, Andrew J. O.
Pennell, Craig E.
Heinrich, Joachim
Plomin, Robert
Smith, George Davey
Tiemeier, Henning
Posthuma, Danielle
Boomsma, Dorret I.
Title A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts
Journal name Journal of the American Academy of Child and Adolescent Psychiatry   Check publisher's open access policy
ISSN 1527-5418
0890-8567
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1016/j.jaac.2016.05.025
Open Access Status Not yet assessed
Volume 55
Issue 10
Start page 896
End page 905.e6
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Collection year 2017
Language eng
Formatted abstract
Objective: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis.

Method: Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated.

Results: SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10−6 and 2.66 × 10−6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96.

Conclusion: The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants.
Keyword ADHD symptoms
Attention problems
GWA
Meta-analysis
SNP heritability
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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