Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe

Livrables

How to analyze causality of environmental factors and epigenetics: In the first part of this course, the ESRs will learn which methods can be used to analyze whether associations between risk factors and mental health symptoms are causal. The second part will focus on the analyses of epigenetic data.

Wprkshop 6

Data sharing and drug target validation: After this course, ESRs know which methods are available to jointly analyze data of several cohorts without the need to share all data. In the second part of this course, methods to identify potential targets for drug treatment, either via repurposing or via new drug development, based on results from genetic analyses will be discussed.

Workshop 1

Statistical genetics – twin studies: The twin methodology will be explained and hands-on experience will be provided by practical’s with the commonly used software. This is an ongoing course.

Annual meeting 2

During the meetings, research project findings will be exchanged, mainly by presentations of the ESRs. They will be open to a wider scientific audience. This will also teach the ESRs in presentation skillsin order optimize science divulgation to an attending audience.

workshop 3

Childhood and adolescent psychopathology – description and course: This course will focus on the common childhood and adolescent psychiatric disorders and provide knowledge on the main symptoms and the prognosis.

International Open conference

in an open conference, open for a broad audience, the results of CAPICE will be presented.

Presentation of ESRs

All ESRs have presented their results at the annual meetings and at conferences.

workshop 4

Longitudinal and multivariate modeling: The use of twin studies as well as polygenic analyses using SNPs for longitudinal and multivariate analyses will be discussed and practiced in the practical’s.

workshop 8

Finding a job in Academia or Industry: This workshop will focus on planning research, research management, CV writing, finding a job in academia, how to get funded, grant writing, how to find a job in industry, management, setting up a company, and leadership.

Workshop 7

Statistical genetics – latest developments: Given the rapid pace of development of statistical methods to analyze genetic data, at the end of the project a course will focus on these new developments. Obviously, the content will be based on these developments.

workshop 2

Statistical genetics – genome-wide association studies: After the course, the ESRs will be able to perform a genome-wide association study. They know the methods to perform polygenic analyses and they have knowledge on GWA meta-analyses.

Annual meeting 3

During the meetings, research project findings will be exchanged, mainly by presentations of the ESRs. They will be open to a wider scientific audience. This will also teach the ESRs in presentation skillsin order optimize science divulgation to an attending audience.

Annual meeting 1

During the meetings, research project findings will be exchanged, mainly by presentations of the ESRs. They will be open to a wider scientific audience. This will also teach the ESRs in presentation skillsin order optimize science divulgation to an attending audience.

Website

The results will be made available to scientists, clinicians and the general public. A dynamic and interactive website will be developed, supporting webcasting services. This website will also have a specific part dedicated for patients and their parents. The text for this part will be written in close collaboration with the patient organizations. The information will be translated in several languages so that it is also accessible to the general public of non-english speaking individuals.

Epigenetic analyses

Epigenomewide-association analyses will be conducted to identify DNA methylation signatures of both lifestyle behaviours during pregnancy and offspring outcomes, to identify potential epigenetic pathways through which lifestyle behaviours may influence offspring outcomes.

Mendelian randomization epigenetic analyses

Mendelian randomization techniques will be used to explore whether methylation of the child’s DNA at birth underlies the association between environmental exposures during pregnancy and psychopathology in childhood and adolescence.

Review paper

Review paper on the latest achievements in genetics, epigenetics and transcriptomic research, that will also be translated from English to Dutch, Swedish and Italian so that they will be published in the national journals that are widely read by clinicians.

Drug target validation analyses

The genetic variants implicated in the WPs will be assessed using genetic circuit mapping technology to implicate molecular pathways relevant to the pathogenesis of mood disorders

Polygenic risk scores

Polygenic risk scores are available for each cohort

PHD Publications ESR2
Multivariate analyses

Harmonized phenotypes in twins will be analyzed within age groups by genetic epidemiological multivariate analyses. Genetic correlations will be computed between the different types of mental health symptoms.

PhD Publications ESR6

Publications for thesis of ESR6

PhD Publications ESR9

Publications for thesis ESR9

Final Report

Final report is sent to the EC summarizing all research, training, and impact.

Longitudinal analyses

Longitudinal, multivariate epidemiological analyses will be performed on twin data to study to what extent different types of mental-health problems co-develop, with a particular focus to what extent the same genotypic variance underlies the stability in different mental-health problems.

Progress report 1

Interim report is sent to the EC describing progress in research, training, and impact.

PhD Publications ESR5

Publications for thesis ESR5

PhD Publications ESR12

Publications for thesis ESR12

PhD Publications ESR10

Publications for thesis ESR10

Progress report 2

Interim report is sent to the EC describing progress in research, training, and impact.

PhD Publications ESR3

Publications ready for thesis ESR3

Validated prediction model for internalizing problems

Using results from the (epi)genetic and environmental risk factors identified in the other WPs a prediction model will be developed for internalizing problems that can be used in clinical practice.

Validated prediction model for ADHD

Using results from the (epi)genetic and environmental risk factors identified in the other WPs a prediction model that can be used in clinical practice will be developed for ADHD

PhD Publications ESR4

Publications ready for thesis ESR4

Gene-environment interaction analyses

Omnibus tests will be performed to test for the presence of environmental effects that are sensitive to and interact with genotypic effects. Next, specific genetic and environmental stressors will be used to test the negative effects of environmental factors that are exacerbated by having specific genetic variants. These analyses will be based on harmonized phenotypes.

Mendelian randomization analyses

Mendelian randomization analyses will be conducted, using either single variants or polygenic risk scores robustly associated with lifestyle behaviours, to identify causal pathways between lifestyle behaviours during pregnancy and offspring outcomes.

PhD Publications ESR11
PhD Publications ESR7

Publications for thesis of ESR7

Polygenic analyses

Analyze how the joint effect of all SNPs is of influence on co-morbidity, overlap in effects between ages and the genetic associations with other phenotypes. Methods that will be used are polygenic risk score analyses and GREML.

Progress report 3

Interim report is sent to the EC describing progress in research, training, and impact.

PhD Publications ESR8

Publications for thesis ESR8

PHD Publications ESR1

Publications ready for thesis ESR1

Genome-wide association meta-analyses

For each phenotype, meta-analyses will be performed for the data available at childhood and at adolescence. This will first be done using linear regression. At a later stage, more advanced analyses will be performed using co-morbidity and longitudinal models. Meta-analyses will also be performed on the harmonized phenotypes for age 10

Harmonized scores

Within each cohort and within each age group, phenotypic data from various measurement instruments will be harmonized in such a way that all subjects have scores on the same scale.

Publications

Time to cut the cord: recognizing and addressing the imbalance of DOHaD research towards the study of maternal pregnancy exposures

Auteurs: G. C. Sharp, L. Schellhas, S. S. Richardson, D. A. Lawlor
Publié dans: Journal of Developmental Origins of Health and Disease, Numéro 10/5, 2019, Page(s) 509-512, ISSN 2040-1744
Éditeur: Cambridge University Press
DOI: 10.1017/s2040174419000072

Association of Youth Depression With Subsequent Somatic Diseases and Premature Death

Auteurs: Marica Leone, Ralf Kuja-Halkola, Amy Leval, Brian M. D’Onofrio, Henrik Larsson, Paul Lichtenstein, Sarah E. Bergen
Publié dans: JAMA Psychiatry, Numéro 78/3, 2021, Page(s) 302, ISSN 2168-622X
Éditeur: American Medical Association
DOI: 10.1001/jamapsychiatry.2020.3786

Characterization of alcohol polygenic risk scores in the context of mental health outcomes: Within-individual and intergenerational analyses in the Avon Longitudinal Study of Parents and Children

Auteurs: Kayleigh E. Easey, Robyn E. Wootton, Hannah M. Sallis, Elis Haan, Laura Schellhas, Marcus R. Munafò, Nicholas J. Timpson, Luisa Zuccolo
Publié dans: Drug and Alcohol Dependence, Numéro 221, 2021, Page(s) 108654, ISSN 0376-8716
Éditeur: Elsevier BV
DOI: 10.1016/j.drugalcdep.2021.108654

Overview of CAPICE—Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe—an EU Marie Skłodowska-Curie International Training Network

Auteurs: Hema Sekhar Reddy Rajula, Mirko Manchia, Kratika Agarwal, Wonuola A. Akingbuwa, Andrea G. Allegrini, Elizabeth Diemer, Sabrina Doering, Elis Haan, Eshim S. Jami, Ville Karhunen, Marica Leone, Laura Schellhas, Ashley Thompson, Stéphanie M. van den Berg, Sarah E. Bergen, Ralf Kuja-Halkola, Anke R. Hammerschlag, Marjo Riitta Järvelin, Amy Leval, Paul Lichtenstein, Sebastian Lundstrom, Matteo Mauri,
Publié dans: European Child & Adolescent Psychiatry, 2021, ISSN 1018-8827
Éditeur: Dr. Dietrich Steinkopff Verlag
DOI: 10.1007/s00787-020-01713-2

Anxiety at age 15 predicts psychiatric diagnoses and suicidal ideation in late adolescence and young adulthood: results from two longitudinal studies

Auteurs: Sabrina Doering, Paul Lichtenstein, Christopher Gillberg, Christel M. Middeldorp, Meike Bartels, Ralf Kuja-Halkola, Sebastian Lundström
Publié dans: BMC Psychiatry, Numéro 19/1, 2019, ISSN 1471-244X
Éditeur: BioMed Central
DOI: 10.1186/s12888-019-2349-3

Machine Learning-Based DNA Methylation Score for Fetal Exposure to Maternal Smoking: Development and Validation in Samples Collected from Adolescents and Adults

Auteurs: Sebastian Rauschert, Phillip E. Melton, Anni Heiskala, Ville Karhunen, Graham Burdge, Jeffrey M. Craig, Keith M. Godfrey, Karen Lillycrop, Trevor A. Mori, Lawrence J. Beilin, Wendy H. Oddy, Craig Pennell, Marjo-Riitta Järvelin, Sylvain Sebert, Rae-Chi Huang
Publié dans: Environmental Health Perspectives, Numéro 128/9, 2020, Page(s) 097003, ISSN 0091-6765
Éditeur: US Department of Health and Human Services
DOI: 10.1289/ehp6076

Urate, Blood Pressure, and Cardiovascular Disease

Auteurs: Dipender Gill, Alan C. Cameron, Stephen Burgess, Xue Li, Daniel J. Doherty, Ville Karhunen, Azmil H. Abdul-Rahim, Martin Taylor-Rowan, Verena Zuber, Philip S. Tsao, Derek Klarin, Evangelos Evangelou, Paul Elliott, Scott M. Damrauer, Terence J. Quinn, Abbas Dehghan, Evropi Theodoratou, Jesse Dawson, Ioanna Tzoulaki
Publié dans: Hypertension, Numéro 77/2, 2021, Page(s) 383-392, ISSN 0194-911X
Éditeur: Lippincott Williams & Wilkins Ltd.
DOI: 10.1161/hypertensionaha.120.16547

Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals

Auteurs: Wonuola A. Akingbuwa, Anke R. Hammerschlag, Eshim S. Jami, Andrea G. Allegrini, Ville Karhunen, Hannah Sallis, Helga Ask, Ragna B. Askeland, Bart Baselmans, Elizabeth Diemer, Fiona A. Hagenbeek, Alexandra Havdahl, Jouke-Jan Hottenga, Hamdi Mbarek, Fernando Rivadeneira, Martin Tesli, Catharina van Beijsterveldt, Gerome Breen, Cathryn M. Lewis, Anita Thapar, Dorret I. Boomsma, Ralf Kuja-Halkola, Ted
Publié dans: JAMA Psychiatry, Numéro 77/7, 2020, Page(s) 715, ISSN 2168-622X
Éditeur: American Medical Association
DOI: 10.1001/jamapsychiatry.2020.0527

Comparison of Conventional Statistical Methods with Machine Learning in Medicine: Diagnosis, Drug Development, and Treatment

Auteurs: Hema Sekhar Reddy Rajula, Giuseppe Verlato, Mirko Manchia, Nadia Antonucci, Vassilios Fanos
Publié dans: Medicina, Numéro 56/9, 2020, Page(s) 455, ISSN 1648-9144
Éditeur: MDPI
DOI: 10.3390/medicina56090455

Scale-free networks in metabolomics

Auteurs: Hema Sekhar Reddy Rajula, Matteo Mauri, Vassilios Fanos
Publié dans: Bioinformation, Numéro 14/03, 2018, Page(s) 140-144, ISSN 0973-8894
Éditeur: Biomedical Informatics
DOI: 10.6026/97320630014140

Genomic prediction of cognitive traits in childhood and adolescence

Auteurs: A. G. Allegrini, S. Selzam, K. Rimfeld, S. von Stumm, J. B. Pingault, R. Plomin
Publié dans: Molecular Psychiatry, Numéro 24/6, 2019, Page(s) 819-827, ISSN 1359-4184
Éditeur: Nature Publishing Group
DOI: 10.1038/s41380-019-0394-4

The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence

Auteurs: Andrea G. Allegrini, Rosa Cheesman, Kaili Rimfeld, Saskia Selzam, Jean‐Baptiste Pingault, Thalia C. Eley, Robert Plomin
Publié dans: Journal of Child Psychology and Psychiatry, Numéro 61/1, 2019, Page(s) 30-39, ISSN 0021-9630
Éditeur: Blackwell Publishing Inc.
DOI: 10.1111/jcpp.13113

Predicting mental health problems in adolescence using machine learning techniques

Auteurs: Ashley E. Tate, Ryan C. McCabe, Henrik Larsson, Sebastian Lundström, Paul Lichtenstein, Ralf Kuja-Halkola
Publié dans: PLOS ONE, Numéro 15/4, 2020, Page(s) e0230389, ISSN 1932-6203
Éditeur: Public Library of Science
DOI: 10.1371/journal.pone.0230389

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Auteurs: Alexessander Couto Alves, N. Maneka G. De Silva, Ville Karhunen, Ulla Sovio, Shikta Das, H. Rob Taal, Nicole M. Warrington, Alexandra M. Lewin, Marika Kaakinen, Diana L. Cousminer, Elisabeth Thiering, Nicholas J. Timpson, Tom A. Bond, Estelle Lowry, Christopher D. Brown, Xavier Estivill, Virpi Lindi, Jonathan P. Bradfield, Frank Geller, Doug Speed, Lachlan J. M. Coin, Marie Loh, Sheila J. Barton,
Publié dans: Science Advances, Numéro 5/9, 2019, Page(s) eaaw3095, ISSN 2375-2548
Éditeur: AAAS
DOI: 10.1126/sciadv.aaw3095

DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

Auteurs: Petri Wiklund, Ville Karhunen, Rebecca C. Richmond, Priyanka Parmar, Alina Rodriguez, Maneka De Silva, Matthias Wielscher, Faisal I. Rezwan, Tom G. Richardson, Juha Veijola, Karl-Heinz Herzig, John W. Holloway, Caroline L. Relton, Sylvain Sebert, Marjo-Riitta Järvelin
Publié dans: Clinical Epigenetics, Numéro 11/1, 2019, ISSN 1868-7075
Éditeur: Springer Verlag
DOI: 10.1186/s13148-019-0683-4

Exploring the role of genetic confounding in the association between maternal and offspring body mass index: evidence from three birth cohorts

Auteurs: Tom A Bond, Ville Karhunen, Matthias Wielscher, Juha Auvinen, Minna Männikkö, Sirkka Keinänen-Kiukaanniemi, Marc J Gunter, Janine F Felix, Inga Prokopenko, Jian Yang, Peter M Visscher, David M Evans, Sylvain Sebert, Alex Lewin, Paul F O’Reilly, Debbie A Lawlor, Marjo-Riitta Jarvelin
Publié dans: International Journal of Epidemiology, Numéro 49/1, 2019, Page(s) 233-243, ISSN 0300-5771
Éditeur: Oxford University Press
DOI: 10.1093/ije/dyz095

Multivariable G-E interplay in the prediction of educational achievement

Auteurs: Andrea G. Allegrini, Ville Karhunen, Jonathan R. I. Coleman, Saskia Selzam, Kaili Rimfeld, Sophie von Stumm, Jean-Baptiste Pingault, Robert Plomin
Publié dans: PLOS Genetics, Numéro 16/11, 2020, Page(s) e1009153, ISSN 1553-7404
Éditeur: PLOS
DOI: 10.1371/journal.pgen.1009153

Overview of Federated Facility to Harmonize, Analyze and Management of Missing Data in Cohorts

Auteurs: Hema Sekhar Reddy Rajula, Veronika Odintsova, Mirko Manchia, Vassilios Fanos
Publié dans: Applied Sciences, Numéro 9/19, 2019, Page(s) 4103, ISSN 2076-3417
Éditeur: MDPI
DOI: 10.3390/app9194103

Metabolic profiles of socio-economic position: a multi-cohort analysis

Auteurs: Oliver Robinson, Alice R Carter, Mika Ala-Korpela, Juan P Casas, Nishi Chaturvedi, Jorgen Engmann, Laura D Howe, Alun D Hughes, Marjo-Riitta Järvelin, Mika Kähönen, Ville Karhunen, Diana Kuh, Tina Shah, Yoav Ben-Shlomo, Reecha Sofat, Chung-Ho E Lau, Terho Lehtimäki, Usha Menon, Olli Raitakari, Andy Ryan, Rui Providencia, Stephanie Smith, Julie Taylor, Therese Tillin, Jorma Viikari, Andrew Wong
Publié dans: International Journal of Epidemiology, 2020, ISSN 0300-5771
Éditeur: Oxford University Press
DOI: 10.1093/ije/dyaa188

ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study

Auteurs: Dipender Gill, Marios Arvanitis, Paul Carter, Ana I. Hernández Cordero, Brian Jo, Ville Karhunen, Susanna C. Larsson, Xuan Li, Sam M. Lockhart, Amy Mason, Evanthia Pashos, Ashis Saha, Vanessa Y. Tan, Verena Zuber, Yohan Bossé, Sarah Fahle, Ke Hao, Tao Jiang, Philippe Joubert, Alan C. Lunt, Willem Hendrik Ouwehand, David J. Roberts, Wim Timens, Maarten van den Berge, Nicholas A. Watkins, Alexis B
Publié dans: Royal Society Open Science, Numéro 7/11, 2020, Page(s) 200958, ISSN 2054-5703
Éditeur: The Royal Society
DOI: 10.1098/rsos.200958

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