Ethics approval and consent to participate
All individuals or their legal representatives gave their written informed consent. All procedures were carried out according to the Declaration of Helsinki. Regarding the access to the cohorts and databases, approvals were obtained from the involved institutions. All data were deidentified.
Consent for publication
Availability of data and materials
Data from the SSC, Generation Scotland and Imagen are available upon request to the promoter of the respective study. Data from the MSSNG database can be accessed through Google Genomics (for access, see http://mss.ng/researchers).
Access to the genetic and phenotypic data for SPARK was obtained from the SFARI Base. Approved researchers may obtain this population dataset (further details available at https://www.sfari.org/resource/spark/) by applying at https://base. sfari.org.
Access to the individual-level genotype and phenotype data for UKBB are available by application (http://www.ukbiobank.ac.uk/)
All the authors declare they have no competing interests.
The analysis of the Pakistani family was supported by a CIHR operating grant to Lan Xiong, and Guy A. Rouleau. Bioinformatic analyses were supported by the Canadian Institutes of Health Research (CIHR). ZS is funded by the Transforming Autism Care Consortium, a thematic network supported by the Fonds de Recherche Québec-Santé. CL is funded by the Vanier Graduate Scholarship. JPR is funded by a Canadian Institutes of Health Research (CIHR) Frederick Banting & Charles Best Canada Graduate Scholarship (FRN159279). CH was supported by an MRC Human Genetics Unit programme grant ‘Quantitative traits in health and disease’ (U. MC_UU_00007/10). GAR holds a Canada Research Chair in Genetics of the Nervous System and the Wilder Penfield Chair in Neurosciences and is supported by a Canadian Institutes of Health Research Foundation Scheme Grant #332971. BC has received a postdoctoral fellowship from the Healthy Brains for Healthy Lives project (Talent program) and a grant from Fondation Bettencourt-Schueller.
ZS, GH, SJ and BC designed the study. SJ, PAD, LX, GAR and BC obtained the funding and supervised the study. ZS, GH, QH, AMJ, SJ, and LX collected the data. CH curated and contributed the Generation Scotland data. HL, AB, SD, AH, and GH curated and contributed to the IMAGEN data. ZS, GH, QH, AMJ, MAB, ED, CL, JPR, ADL, DS and BC analyzed the data. ZS, GH, MAL, PAD, GAR and BC interpreted the data. ZS, GH, QH, PAD, GAR and BC drafted the report. All authors contributed to and have approved the final manuscript.
We would like to thank Brohi Qasim who recruited the Pakistani family and Lydia Werhli, who contributed to the analyses about the Pakistani family during her IFMSA Exchange program.
This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from [email protected] Funding for the project was provided by the Wellcome Trust.
Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z).
IMAGEN received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313), Human Brain Project (HBP SGA 2, 785907, and HBP SGA 3, 945539), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the National Institute of Health (NIH) (R01DA049238, A decentralized macro and micro gene-by-environment interaction analysis of substance use behavior and its brain biomarkers), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; Forschungsnetz AERIAL 01EE1406A, 01EE1406B; Forschungsnetz IMAC-Mind 01GL1745B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940, TRR 265, NE 1383/14-1), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), the National Institutes of Health (NIH) funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01). Further support was provided by grants from: – the ANR (ANR-12-SAMA-0004, AAPG2019 – GeBra), the Eranet Neuron (AF12-NEUR0008-01 – WM2NA; and ANR-18-NEUR00002-01 – ADORe), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the Fondation de l’Avenir (grant AP-RM-17-013 ), the Fédération pour la Recherche sur le Cerveau; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), U.S.A. (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence.