Journal of the American Academy of Child & Adolescent Psychiatry
New researchA Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts
Section snippets
Cohorts
The EArly Genetics and Life course Epidemiology (EAGLE) consortium is a collaboration among several population-based birth cohorts from Europe, Australia, and the United States (http://www.wikigenes.org/e/art/e/348.html). The consortium focuses on a wide range of phenotypes in childhood.20, 21 EAGLE cohorts with ADHD symptom scores in childhood (age at measurement <13 years) were invited to participate in the meta-analysis. An overview of the nine cohorts included in the meta-analysis is
SNP-Based Heritability
The estimates of the SNP-based heritability are shown in Table 2. The estimates for the maternal ratings were 5% (not significant) for preschool SDQ and 13% (not significant) and 14% (p < .05) for preschool CBCL and school-age SDQ, respectively. For teacher ratings, an SNP-based heritability of 34% (p < .05) was observed. These results indicated that SNPs tag variants associated with various ADHD symptom scores.
SNP- and Gene-Based Meta-Analyses
The numbers of SNPs from each cohort that were included in the meta-analysis after
Discussion
The current study comprised the largest GWA analysis of continuous ADHD symptom scores in children to date. We found that common variants included in GWA studies explained variation in ADHD symptom scores assessed in the general population. The SNP heritability estimates for the various measures from the participating cohorts ranged from 0.05 to 0.34. The SNP heritability based on the results of the meta-analysis in all cohorts with a total of 17,666 children was estimated at 8%. We did not
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This article is discussed in an editorial by Dr. Samuele Cortese on page 839.
ALSPAC: The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and they will serve as guarantors for the contents of this paper. GWAS data were generated by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe.
Generation R: The Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), and the Ministry of Health, Welfare and Sport. H.T. received additional grants from the Netherlands Organization for Health Research and Development (ZonMw VIDI 017.106.370). The work of A.H. and D.P. was supported by a grant from the Dutch Scientific Organisation for Scientific Research (NWO 433- 09-228 and 453-14-005).
GINI/LISA: Personal and financial support by the Munich Center of Health Sciences (MCHEALTH) as part of the Ludwig-Maximilians University Munich LMU innovative is gratefully acknowledged.
INMA: This study was funded by grants from the Spanish Instituto de Salud Carlos III (CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, PI061756, PI091958, and PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, CP11/0178 and MS13/00054), Spanish Ministry of Science and Innovation (SAF2008-00357), European Commission (ENGAGE project and grant agreement HEALTH-F4-2007- 201413, HEALTH.2010.2.4.5-1, FP7-ENV-2011 cod 282957), Fundació La Marató de TV3, Generalitat de Catalunya-CIRIT 1999SGR 00241, and Conselleria de Sanitat Generalitat Valenciana. Part of the DNA extractions and genotyping was performed at the Spanish National Genotyping Centre (CEGENBarcelona). N. Vilor-Tejedor thanks the Agència de Gestió d’Ajuts Universitaris i de Recerca - Generalitat de Catalunya for her pre-doctoral grant (2015 FI_B 00636).
MoBa (Mother and Child Cohort of NIPH): This work was supported by grants from the Norwegian Research Council (FUGE 183220/S10, FRIMEDKLI-05 ES236011), Swedish Medical Society (SLS 2008-21198), Jane and Dan Olsson Foundations, and Swedish government grants to researchers in the public health service (ALFGBG-2863, ALFGBG-11522, ALFGBG-426411), and the European Community’s Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4- 2007-201413. The Norwegian Mother and Child Cohort Study was also supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537-01 and grant no.2 UO1 NS 047537-06A1), and the Norwegian Research Council/FUGE (grant no. 151918/S10). Researchers interested in using MoBa data must obtain approval from the Scientific Management Committee of MoBa and from the Regional Committee for Medical and Health Research Ethics for access to data and biological material. Researchers are required to follow the terms of an Assistance Agreement containing a number of clauses designed to ensure protection of privacy and compliance with relevant laws. For further information, contact the principal investigator of MoBa, Per Magnus ([email protected]).
The Netherlands Twin Register: Genetics of Mental Illness (European Research Council ERC-230374); Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMW 91210020); Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); VU University’s Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); Community's Seventh Framework Program (FP7/2007-2013); ENGAGE (HEALTH-F4-2007-201413); the Avera Institute, Sioux Falls, South Dakota, USA, and Grand Opportunity (grants 1RC2 MH089951 and 1RC2 MH089995).
Psychiatric Genomics Consortium ADHD Working Group Members: Richard J.L. Anney, PhD, Alejandro Arias Vasquez, PhD, Philip Asherson, MD, Tobias J. Banaschewski, MD, PhD, Mònica Bayés, PhD, Joseph Biederman, MD, Jan K. Buitelaar, MD, PhD, Miguel Casas, MD, PhD, Alice Charach, MD, MSc, Bru Cormand, PhD, Jennifer Crosbie, PhD, Mark J. Daly, PhD, Alysa E. Doyle, PhD, Richard P. Ebstein, PhD, Josephine Elia, MD, Stephen V. Faraone, PhD, Barbara Franke, PhD, Christine Freitag, MD, MA, Michael Gill, MbBCh BAO, MD, MRCPsych, FTCD, Hakon Hakonarson, MD, PhD, Peter Holmans, PhD, Lindsey Kent, MD, Jonna Kuntsi, PhD, Nanda Lambregts-Rommelse, PhD, Kate Langley, PhD, Klaus-Peter Lesch, MD, Sandra K. Loo, PhD, James J. McGough, MD, Sarah E. Medland, PhD, Jobst Meyer, PhD, Eric Mick, ScD, Ana Miranda, MD, Fernando Mulas, MD, PhD, Benjamin M. Neale, PhD, Stan F. Nelson, MD, Michael C. O’Donovan, FRCPsych, PhD, Robert D. Oades, PhD, Michael J. Owen, PhD, Haukur Palmason, PhD, Josep Antoni Ramos-Quiroga, MD, PhD, Andreas Reif, MD, Tobias J. Renner, MD, Marta Ribasés, PhD, Stephan Ripke, MD, Olga Rivero, PhD, Herbert Roeyers, MD, PhD, Jasmin Romanos, MD, Marcel Romanos, MD, Aribert Rothenberger, MD, Cristina Sánchez-Mora, PhD, Russell Schachar, MD, Joseph Sergeant, PhD, Susan L. Smalley, PhD, Edmund J. S. Sonuga-Barke, PhD, Hans-Christoph Steinhausen, MD, PhD, DMSc, Anita Thapar, MBBCh, FRCPsych, PhD, FmedSci, Alexandre Todorov, PhD, Susanne Walitza, MD, Yufeng Wang, MD, PhD, Andreas Warnke, MD, PhD, Nigel Williams, PhD, Yanli Zhang-James, PhD.
Dr. Middeldorp, Ms. Hammerschlag, and Mr. Ouwens contributed equally to this work.
Disclosure: Dr. Hudziak has received grant or research support from the National Institutes of Health, the National Institute of Mental Health, the National Institute of Diabetes and Digestive and Kidney Disease, and the state of Vermont. His primary appointment is with the University of Vermont. He has additional appointments with Erasmus University in Rotterdam, Netherlands, Washington University School of Medicine in St. Louis, Missouri, and the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire. Drs. Middeldorp, Groen-Blokhuis, St Pourcain, Greven, Pappa, Tiesler, Nolte, Ebejer, Zhao, Davies, Ehli, Evans, Guxens, Hottenga, Jugessur, Kemp, Martin, Myhre, Ormel, Ring, Standl, Stergiakouli, Stoltenberg, Thiering, Timpson, Trzaskowski, van der Most, Nyholt, Medland, Neale, Jacobsson, Sunyer, Hartman, Whitehouse, Pennell, Heinrich, Plomin, Smith, Tiemeier, Posthuma, Boomsma, Ms. Hammerschlag, Mr. Ouwens, Mr. Ang, Ms. Vilor-Tejedor, Mr. Bacelis, Ms. Fedko, Ms. Krapohl, Mr. Murcia, and Ms. Wang report no biomedical financial interests or potential conflicts of interest.