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2. Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments

Author

Vainieri, Isabella, Martin, Joanna, Rommel, Anna-Sophie, Asherson, Philip, Banaschewski, Tobias, Buitelaar, Jan, Cormand, Bru, Crosbie, Jennifer, Faraone, Stephen V, Franke, Barbara, Loo, Sandra K, Miranda, Ana, Manor, Iris, Oades, Robert D, Purves, Kirstin L, Ramos-Quiroga, J Antoni, Ribasés, Marta, Roeyers, Herbert, Rothenberger, Aribert, Schachar, Russell, Sergeant, Joseph, Steinhausen, Hans-Christoph, Vuijk, Pieter J, Doyle, Alysa E, and Kuntsi, Jonna

Subjects
Attention Deficit Hyperactivity Disorder (ADHD), Genetics, Prevention, Human Genome, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Child, Humans, Young Adult, Attention Deficit Disorder with Hyperactivity, Cognitive Dysfunction, Genome-Wide Association Study, Phenotype, Reaction Time, Case-Control Studies, ADHD, attention, cognition, inhibition, polygenic risk scores, reaction time variability, Neurosciences, Public Health and Health Services, Psychology, Psychiatry
Abstract

BackgroundA recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).MethodsThe discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.ResultsWhen combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).ConclusionsWe detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

Published
2022

3. Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

Author

Kong, Xiang‐Zhen, Mathias, Samuel R, Guadalupe, Tulio, Abé, Christoph, Agartz, Ingrid, Akudjedu, Theophilus N, Aleman, Andre, Alhusaini, Saud, Allen, Nicholas B, Ames, David, Andreassen, Ole A, Vasquez, Alejandro Arias, Armstrong, Nicola J, Asherson, Phil, Bergo, Felipe, Bastin, Mark E, Batalla, Albert, Bauer, Jochen, Baune, Bernhard T, Baur‐Streubel, Ramona, Biederman, Joseph, Blaine, Sara K, Boedhoe, Premika, Bøen, Erlend, Bose, Anushree, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J, Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales‐Rodríguez, Erick Jorge, Cannon, Dara M, Caparelli, Elisabeth C, Castellanos, Francisco X, Cendes, Fernando, Chaim‐Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun‐lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Córdova‐Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, de Bruttopilo, Sara Ambrosino, de Zeeuw, Patrick, Deary, Ian J, Demeter, Damion V, Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, Nhat Trung, Doherty, Colin P, Doyle, Alysa, Durston, Sarah, Earl, Eric, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N, Fair, Damien A, Faraone, Stephen V, Fernández, Guillén, Flint, Claas, Filho, Geraldo Busatto, Förster, Katharina, Fouche, Jean‐Paul, Foxe, John J, Frodl, Thomas, Fuentes‐Claramonte, Paola, Fullerton, Janice M, Garavan, Hugh, do Santos Garcia, Danielle, Gotlib, Ian H, Goudriaan, Anna E, Grabe, Hans Jörgen, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K, Harris, Mathew A, Hartman, Catharina A, del Carmen Valdés Hernández, Maria, and Heslenfeld, Dirk

Subjects
Biological Psychology, Psychology, Neurosciences, Neurological, Adolescent, Adult, Aged, Brain Cortical Thickness, Cerebral Cortex, Datasets as Topic, Humans, Magnetic Resonance Imaging, Middle Aged, Multicenter Studies as Topic, Neuroimaging, Publication Bias, Reproducibility of Results, Young Adult, ENIGMA Laterality Working Group, P-hacking, multisite collaboration, publication bias, reproducibility, team science, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.

Published
2022

4. Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets

Author

Postema, Merel C, Hoogman, Martine, Ambrosino, Sara, Asherson, Philip, Banaschewski, Tobias, Bandeira, Cibele E, Baranov, Alexandr, Bau, Claiton HD, Baumeister, Sarah, Baur‐Streubel, Ramona, Bellgrove, Mark A, Biederman, Joseph, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Buitelaar, Jan K, Busatto, Geraldo F, Castellanos, Francisco X, Cercignani, Mara, Chaim‐Avancini, Tiffany M, Chantiluke, Kaylita C, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Cupertino, Renata B, de Zeeuw, Patrick, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Epstein, Jeffery N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Frodl, Thomas, Gabel, Matt C, Gogberashvili, Tinatin, Grevet, Eugenio H, Haavik, Jan, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hoekstra, Pieter J, Hohmann, Sarah, Høvik, Marie F, Jernigan, Terry L, Kardatzki, Bernd, Karkashadze, Georgii, Kelly, Clare, Kohls, Gregor, Konrad, Kerstin, Kuntsi, Jonna, Lazaro, Luisa, Lera‐Miguel, Sara, Lesch, Klaus‐Peter, Louza, Mario R, Lundervold, Astri J, Malpas, Charles B, Mattos, Paulo, McCarthy, Hazel, Namazova‐Baranova, Leyla, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Weiss, Eileen Oberwelland, Tuura, Ruth L O'Gorman, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A, Plessen, Kerstin J, Ramos‐Quiroga, J Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro GP, Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne JS, Seitz, Jochen, Shaw, Philip, Silk, Tim J, Skokauskas, Norbert, Vila, Juan C Soliva, Stevens, Michael C, Sudre, Gustavo, Tamm, Leanne, Tovar‐Moll, Fernanda, van Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, Glahn, David C, and Jahanshad, Neda

Subjects
Biological Psychology, Psychology, Brain Disorders, Mental Illness, Mental Health, Pediatric, Clinical Research, Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Neurosciences, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Brain, Caudate Nucleus, Child, Humans, Magnetic Resonance Imaging, Attention&#8208, deficit, hyperactivity disorder, brain asymmetry, brain laterality, structural MRI, large&#8208, scale data, ENIGMA ADHD Working Group, Attention-deficit, large-scale data, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Published
2021

6. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, Premika SW, van Rooij, Daan, Hoogman, Martine, Twisk, Jos WR, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobias, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thomas, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, and Kardatzki, Bernd

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Biomedical Imaging, Intellectual and Developmental Disabilities (IDD), Pediatric, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Mental Health, Neurosciences, Autism, Clinical Research, Mental Illness, Behavioral and Social Science, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Mental health, Neurological, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Cerebrum, Child, Female, Human Development, Humans, Male, Neuroimaging, Obsessive-Compulsive Disorder, Organ Size, Psychopathology, Research Report, Systems Analysis, ENIGMA ADHD working group, ENIGMA ASD working group, ENIGMA OCD working group, Attention Deficit Hyperactivity Disorder, ENIGMA, Structural MRI, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

8. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Consortium, Cross-Disorder Group of the Psychiatric Genomics, Lee, Phil H, Anttila, Verneri, Won, Hyejung, Feng, Yen-Chen A, Rosenthal, Jacob, Zhu, Zhaozhong, Tucker-Drob, Elliot M, Nivard, Michel G, Grotzinger, Andrew D, Posthuma, Danielle, Wang, Meg M-J, Yu, Dongmei, Stahl, Eli A, Walters, Raymond K, Anney, Richard JL, Duncan, Laramie E, Ge, Tian, Adolfsson, Rolf, Banaschewski, Tobias, Belangero, Sintia, Cook, Edwin H, Coppola, Giovanni, Derks, Eske M, Hoekstra, Pieter J, Kaprio, Jaakko, Keski-Rahkonen, Anna, Kirov, George, Kranzler, Henry R, Luykx, Jurjen J, Rohde, Luis A, Zai, Clement C, Agerbo, Esben, Arranz, MJ, Asherson, Philip, Bækvad-Hansen, Marie, Baldursson, Gísli, Bellgrove, Mark, Belliveau, Richard A, Buitelaar, Jan, Burton, Christie L, Bybjerg-Grauholm, Jonas, Casas, Miquel, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Søren, Demontis, Ditte, Doyle, Alysa E, Dumont, Ashley, Elia, Josephine, Grove, Jakob, Gudmundsson, Olafur O, Haavik, Jan, Hakonarson, Hakon, Hansen, Christine S, Hartman, Catharina A, Hawi, Ziarih, Hervás, Amaia, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Leung, Patrick WL, Loo, Sandra K, Martin, Joanna, Martin, Alicia R, McGough, James J, Medland, Sarah E, Moran, Jennifer L, Mors, Ole, Mortensen, Preben B, Oades, Robert D, Palmer, Duncan S, Pedersen, Carsten B, Pedersen, Marianne G, Peters, Triinu, Poterba, Timothy, Poulsen, Jesper B, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Satterstrom, F Kyle, Schachar, Russell, Artigas, Maria Soler, Steinberg, Stacy, Stefansson, Hreinn, Turley, Patrick, Walters, G Bragi, Team, 23andMe Research, Werge, Thomas, Zayats, Tetyana, and Arking, Dan E

Subjects
Neurosciences, Serious Mental Illness, Human Genome, Schizophrenia, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Genetics, Pediatric, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mental Disorders, Neurogenesis, Quantitative Trait Loci, Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu, Cross-Disorder Group of the Psychiatric Genomics Consortium, GWAS, Psychiatric genetics, cross-disorder genetics, functional genomics, gene expression, genetic architecture, genetic correlation, neurodevelopment, pleiotropy, psychiatric disorders, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Published
2019

9. Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

Author

Hoogman, Martine, Muetzel, Ryan, Guimaraes, Joao P, Shumskaya, Elena, Mennes, Maarten, Zwiers, Marcel P, Jahanshad, Neda, Sudre, Gustavo, Wolfers, Thomas, Earl, Eric A, Soliva Vila, Juan Carlos, Vives-Gilabert, Yolanda, Khadka, Sabin, Novotny, Stephanie E, Hartman, Catharina A, Heslenfeld, Dirk J, Schweren, Lizanne JS, Ambrosino, Sara, Oranje, Bob, de Zeeuw, Patrick, Chaim-Avancini, Tiffany M, Rosa, Pedro GP, Zanetti, Marcus V, Malpas, Charles B, Kohls, Gregor, von Polier, Georg G, Seitz, Jochen, Biederman, Joseph, Doyle, Alysa E, Dale, Anders M, van Erp, Theo GM, Epstein, Jeffery N, Jernigan, Terry L, Baur-Streubel, Ramona, Ziegler, Georg C, Zierhut, Kathrin C, Schrantee, Anouk, Høvik, Marie F, Lundervold, Astri J, Kelly, Clare, McCarthy, Hazel, Skokauskas, Norbert, O’Gorman Tuura, Ruth L, Calvo, Anna, Lera-Miguel, Sara, Nicolau, Rosa, Chantiluke, Kaylita C, Christakou, Anastasia, Vance, Alasdair, Cercignani, Mara, Gabel, Matt C, Asherson, Philip, Baumeister, Sarah, Brandeis, Daniel, Hohmann, Sarah, Bramati, Ivanei E, Tovar-Moll, Fernanda, Fallgatter, Andreas J, Kardatzki, Bernd, Schwarz, Lena, Anikin, Anatoly, Baranov, Alexandr, Gogberashvili, Tinatin, Kapilushniy, Dmitry, Solovieva, Anastasia, El Marroun, Hanan, White, Tonya, Karkashadze, Georgii, Namazova-Baranova, Leyla, Ethofer, Thomas, Mattos, Paulo, Banaschewski, Tobias, Coghill, David, Plessen, Kerstin J, Kuntsi, Jonna, Mehta, Mitul A, Paloyelis, Yannis, Harrison, Neil A, Bellgrove, Mark A, Silk, Tim J, Cubillo, Ana I, Rubia, Katya, Lazaro, Luisa, Brem, Silvia, Walitza, Susanne, Frodl, Thomas, Zentis, Mariam, Castellanos, Francisco X, Yoncheva, Yuliya N, Haavik, Jan, Reneman, Liesbeth, Conzelmann, Annette, Lesch, Klaus-Peter, Pauli, Paul, Reif, Andreas, Tamm, Leanne, Konrad, Kerstin, Oberwelland Weiss, Eileen, Busatto, Geraldo F, and Louza, Mario R

Subjects
Biological Psychology, Psychology, Biomedical Imaging, Mental Illness, Neurosciences, Behavioral and Social Science, Mental Health, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Pediatric, Clinical Research, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Age Factors, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Cerebral Cortex, Child, Child, Preschool, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Psychiatric Status Rating Scales, Sex Factors, Young Adult, Attention Deficit Hyperactivity Disorder, Cortical Surface Area, Cortical Thickness, Imaging, Meta-Analysis, Neuroanatomy, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

ObjectiveNeuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.MethodsCortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).ResultsIn the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.ConclusionsSubtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

Published
2019

11. Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium

Author

Kong, Xiang-Zhen, Mathias, Samuel R, Guadalupe, Tulio, Glahn, David C, Franke, Barbara, Crivello, Fabrice, Tzourio-Mazoyer, Nathalie, Fisher, Simon E, Thompson, Paul M, Francks, Clyde, Abé, Christoph, Agartz, Ingrid, Akudjedu, Theophilus N, Aleman, Andre, Alhusaini, Saud, Allen, Nicholas B, Ames, David, Andreassen, Ole A, Vasquez, Alejandro Arias, Armstrong, Nicola J, Bergo, Felipe, Bastin, Mark E, Batalla, Albert, Bauer, Jochen, Baune, Bernhard T, Baur-Streubel, Ramona, Biederman, Joseph, Blaine, Sara K, Boedhoe, Premika, Bøen, Erlend, Bose, Anushree, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J, Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Canive, Jose M, Cannon, Dara M, Caparelli, Elisabeth C, Castellanos, Francisco X, Cavalleri, Gianpiero L, Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dale, Anders, Dannlowski, Udo, Ambrosino de Bruttopilo, Sara, de Zeeuw, Patrick, Deary, Ian J, Delanty, Norman, Demeter, Damion V, Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, N Trung, Doherty, Colin P, Doyle, Alysa, Durston, Sarah, Earl, Eric, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N, Fair, Damien A, Faraone, Stephen V, Fernández, Guillén, Filho, Geraldo Busatto, Förster, Katharina, Fouche, Jean-Paul, Foxe, John J, Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice, Garavan, Hugh, Garcia, Danielle do Santos, Gotlib, Ian H, Goudriaan, Anna E, and Grabe, Hans Jörgen

Subjects
Neurosciences, Clinical Research, Brain Disorders, Mental Health, Biomedical Imaging, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Mental health, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Child, Preschool, Databases, Factual, Female, Humans, Infant, Male, Middle Aged, Neuroimaging, Young Adult, brain asymmetry, lateralization, cortical thickness, surface area, meta-analysis, ENIGMA Laterality Working Group
Abstract

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

Published
2018

13. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis

Author

Hoogman, Martine, Bralten, Janita, Hibar, Derrek P, Mennes, Maarten, Zwiers, Marcel P, Schweren, Lizanne SJ, van Hulzen, Kimm JE, Medland, Sarah E, Shumskaya, Elena, Jahanshad, Neda, de Zeeuw, Patrick, Szekely, Eszter, Sudre, Gustavo, Wolfers, Thomas, Onnink, Alberdingk MH, Dammers, Janneke T, Mostert, Jeanette C, Vives-Gilabert, Yolanda, Kohls, Gregor, Oberwelland, Eileen, Seitz, Jochen, Schulte-Rüther, Martin, Ambrosino, Sara, Doyle, Alysa E, Høvik, Marie F, Dramsdahl, Margaretha, Tamm, Leanne, van Erp, Theo GM, Dale, Anders, Schork, Andrew, Conzelmann, Annette, Zierhut, Kathrin, Baur, Ramona, McCarthy, Hazel, Yoncheva, Yuliya N, Cubillo, Ana, Chantiluke, Kaylita, Mehta, Mitul A, Paloyelis, Yannis, Hohmann, Sarah, Baumeister, Sarah, Bramati, Ivanei, Mattos, Paulo, Tovar-Moll, Fernanda, Douglas, Pamela, Banaschewski, Tobias, Brandeis, Daniel, Kuntsi, Jonna, Asherson, Philip, Rubia, Katya, Kelly, Clare, Di Martino, Adriana, Milham, Michael P, Castellanos, Francisco X, Frodl, Thomas, Zentis, Mariam, Lesch, Klaus-Peter, Reif, Andreas, Pauli, Paul, Jernigan, Terry L, Haavik, Jan, Plessen, Kerstin J, Lundervold, Astri J, Hugdahl, Kenneth, Seidman, Larry J, Biederman, Joseph, Rommelse, Nanda, Heslenfeld, Dirk J, Hartman, Catharina A, Hoekstra, Pieter J, Oosterlaan, Jaap, von Polier, Georg, Konrad, Kerstin, Vilarroya, Oscar, Ramos-Quiroga, Josep Antoni, Soliva, Joan Carles, Durston, Sarah, Buitelaar, Jan K, Faraone, Stephen V, Shaw, Philip, Thompson, Paul M, and Franke, Barbara

Subjects
Brain Disorders, Neurosciences, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Mental Health, Pediatric, Biomedical Imaging, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Linear Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Young Adult, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

BackgroundNeuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis.MethodsIn this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156.FindingsOur sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5).InterpretationWith the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes.FundingNational Institutes of Health.

Published
2017

15. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Lee, Phil H., Anttila, Verneri, Won, Hyejung, Feng, Yen-Chen A., Rosenthal, Jacob, Zhu, Zhaozhong, Tucker-Drob, Elliot M., Nivard, Michel G., Grotzinger, Andrew D., Posthuma, Danielle, Wang, Meg M.-J., Yu, Dongmei, Stahl, Eli A., Walters, Raymond K., Anney, Richard J.L., Duncan, Laramie E., Ge, Tian, Adolfsson, Rolf, Banaschewski, Tobias, Belangero, Sintia, Cook, Edwin H., Coppola, Giovanni, Derks, Eske M., Hoekstra, Pieter J., Kaprio, Jaakko, Keski-Rahkonen, Anna, Kirov, George, Kranzler, Henry R., Luykx, Jurjen J., Rohde, Luis A., Zai, Clement C., Agerbo, Esben, Arranz, M.J., Asherson, Philip, Bækvad-Hansen, Marie, Baldursson, Gísli, Bellgrove, Mark, Belliveau, Richard A., Jr., Buitelaar, Jan, Burton, Christie L., Bybjerg-Grauholm, Jonas, Casas, Miquel, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Søren, Demontis, Ditte, Doyle, Alysa E., Dumont, Ashley, Elia, Josephine, Grove, Jakob, Gudmundsson, Olafur O., Haavik, Jan, Hakonarson, Hakon, Hansen, Christine S., Hartman, Catharina A., Hawi, Ziarih, Hervás, Amaia, Hougaard, David M., Howrigan, Daniel P., Huang, Hailiang, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Leung, Patrick W.L., Loo, Sandra K., Martin, Joanna, Martin, Alicia R., McGough, James J., Medland, Sarah E., Moran, Jennifer L., Mors, Ole, Mortensen, Preben B., Oades, Robert D., Palmer, Duncan S., Pedersen, Carsten B., Pedersen, Marianne G., Peters, Triinu, Poterba, Timothy, Poulsen, Jesper B., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Satterstrom, F. Kyle, Schachar, Russell, Artigas, Maria Soler, Steinberg, Stacy, Stefansson, Hreinn, Turley, Patrick, Walters, G. Bragi, Werge, Thomas, Zayats, Tetyana, Arking, Dan E., Bettella, Francesco, Buxbaum, Joseph D., Christensen, Jane H., Collins, Ryan L., Coon, Hilary, De Rubeis, Silvia, Delorme, Richard, Grice, Dorothy E., Hansen, Thomas F., Holmans, Peter A., Hope, Sigrun, Hultman, Christina M., Klei, Lambertus, Ladd-Acosta, Christine, Magnusson, Pall, Nærland, Terje, Nyegaard, Mette, Pinto, Dalila, Qvist, Per, Rehnström, Karola, Reichenberg, Abraham, Reichert, Jennifer, Roeder, Kathryn, Rouleau, Guy A., Saemundsen, Evald, Sanders, Stephan J., Sandin, Sven, St Pourcain, Beate, Stefansson, Kari, Sutcliffe, James S., Talkowski, Michael E., Weiss, Lauren A., Willsey, A. Jeremy, Agartz, Ingrid, Akil, Huda, Albani, Diego, Alda, Martin, Als, Thomas D., Anjorin, Adebayo, Backlund, Lena, Bass, Nicholas, Bauer, Michael, Baune, Bernhard T., Bellivier, Frank, Bergen, Sarah E., Berrettini, Wade H., Biernacka, Joanna M., Blackwood, Douglas H.R., Bøen, Erlend, Budde, Monika, Bunney, William, Burmeister, Margit, Byerley, William, Byrne, Enda M., Cichon, Sven, Clarke, Toni-Kim, Coleman, Jonathan R.I., Craddock, Nicholas, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Di Florio, Arianna, Elvsåshagen, Torbjørn, Etain, Bruno, Fischer, Sascha B., Forstner, Andreas J., Forty, Liz, Frank, Josef, Frye, Mark, Fullerton, Janice M., Gade, Katrin, Gaspar, Héléna A., Gershon, Elliot S., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Gordon-Smith, Katherine, Green, Melissa J., Greenwood, Tiffany A., Grigoroiu-Serbanescu, Maria, Guzman-Parra, José, Hauser, Joanna, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hoffmann, Per, Holland, Dominic, Jamain, Stéphane, Jones, Ian, Jones, Lisa A., Kandaswamy, Radhika, Kelsoe, John R., Kennedy, James L., Joachim, Oedegaard Ketil, Kittel-Schneider, Sarah, Kogevinas, Manolis, Koller, Anna C., Lavebratt, Catharina, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Loohuis, Loes M.O., Lucae, Susanne, Maaser, Anna, Malt, Ulrik F., Martin, Nicholas G., Martinsson, Lina, McElroy, Susan L., McMahon, Francis J., McQuillin, Andrew, Melle, Ingrid, Metspalu, Andres, Millischer, Vincent, Mitchell, Philip B., Montgomery, Grant W., Morken, Gunnar, Morris, Derek W., Müller-Myhsok, Bertram, Mullins, Niamh, Myers, Richard M., Nievergelt, Caroline M., Nordentoft, Merete, Adolfsson, Annelie Nordin, Nöthen, Markus M., Ophoff, Roel A., Owen, Michael J., Paciga, Sara A., Pato, Carlos N., Pato, Michele T., Perlis, Roy H., Perry, Amy, Potash, James B., Reinbold, Céline S., Rietschel, Marcella, Rivera, Margarita, Roberson, Mary, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Serretti, Alessandro, Sigurdsson, Engilbert, Smeland, Olav B., Stordal, Eystein, Streit, Fabian, Strohmaier, Jana, Thorgeirsson, Thorgeir E., Treutlein, Jens, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Wang, Yunpeng, Witt, Stephanie H., Zandi, Peter, Adan, Roger A.H., Alfredsson, Lars, Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Perica, Vesna Boraska, Brandt, Harry, Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S.P., Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Docampo, Elisa, Egberts, Karin, Ehrlich, Stefan, Espeseth, Thomas, Fernández-Aranda, Fernando, Fichter, Manfred M., Foretova, Lenka, Forzan, Monica, Gambaro, Giovanni, Giegling, Ina, Gonidakis, Fragiskos, Gorwood, Philip, Mayora, Monica Gratacos, Guo, Yiran, Halmi, Katherine A., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Imgart, Hartmut, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J.H., Kaye, Walter H., Kennedy, Martin A., Kim, Youl-Ri, Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Landén, Mikael, Le Hellard, Stephanie, Levitan, Robert D., Li, Dong, Lichtenstein, Paul, Maj, Mario, Marsal, Sara, McDevitt, Sara, Mitchell, James, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, O’Toole, Julie K., Padyukov, Leonid, Pantel, Jacques, Papezova, Hana, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Roberts, Marion, Rujescu, Dan, Rybakowski, Filip, Scherag, André, Schmidt, Ulrike, Seitz, Jochen, Slachtova, Lenka, Slof-Op‘t Landt, Margarita C.T., Slopien, Agnieszka, Sorbi, Sandro, Southam, Lorraine, Strober, Michael, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tziouvas, Konstantinos, van Elburg, Annemarie A., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Wichmann, H-Erich, Woodside, D. Blake, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Adams, Mark J., Andlauer, Till F.M., Berger, Klaus, Binder, Elisabeth B., Boomsma, Dorret I., Castelao, Enrique, Colodro-Conde, Lucía, Direk, Nese, Docherty, Anna R., Domenici, Enrico, Domschke, Katharina, Dunn, Erin C., Foo, Jerome C., de. Geus, E.J.C., Grabe, Hans J., Hamilton, Steven P., Horn, Carsten, Hottenga, Jouke-Jan, Howard, David, Ising, Marcus, Kloiber, Stefan, Levinson, Douglas F., Lewis, Glyn, Magnusson, Patrik K.E., Mbarek, Hamdi, Middeldorp, Christel M., Mostafavi, Sara, Nyholt, Dale R., Penninx, Brenda WJH., Peterson, Roseann E., Pistis, Giorgio, Porteous, David J., Preisig, Martin, Quiroz, Jorge A., Schaefer, Catherine, Schulte, Eva C., Shi, Jianxin, Smith, Daniel J., Thomson, Pippa A., Tiemeier, Henning, Uher, Rudolf, van der Auwera, Sandra, Weissman, Myrna M., Alexander, Madeline, Begemann, Martin, Bramon, Elvira, Buccola, Nancy G., Cairns, Murray J., Campion, Dominique, Carr, Vaughan J., Cloninger, C. Robert, Cohen, David, Collier, David A., Corvin, Aiden, DeLisi, Lynn E., Donohoe, Gary, Dudbridge, Frank, Duan, Jubao, Freedman, Robert, Gejman, Pablo V., Golimbet, Vera, Godard, Stephanie, Ehrenreich, Hannelore, Hartmann, Annette M., Henskens, Frans A., Ikeda, Masashi, Iwata, Nakao, Jablensky, Assen V., Joa, Inge, Jönsson, Erik G., Kelly, Brian J., Knight, Jo, Konte, Bettina, Laurent-Levinson, Claudine, Lee, Jimmy, Lencz, Todd, Lerer, Bernard, Loughland, Carmel M., Malhotra, Anil K., Mallet, Jacques, McDonald, Colm, Mitjans, Marina, Mowry, Bryan J., Murphy, Kieran C., Murray, Robin M., O’Neill, F. Anthony, Oh, Sang-Yun, Palotie, Aarno, Pantelis, Christos, Pulver, Ann E., Petryshen, Tracey L., Quested, Digby J., Riley, Brien, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Scott, Rodney J., Sham, Pak C., Silverman, Jeremy M., Sim, Kang, Steixner, Agnes A., Tooney, Paul A., van Os, Jim, Vawter, Marquis P., Walsh, Dermot, Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Wormley, Brandon K., Zhang, Fuquan, Androutsos, Christos, Arnold, Paul D., Barr, Cathy L., Barta, Csaba, Bey, Katharina, Bienvenu, O. Joseph, Black, Donald W., Brown, Lawrence W., Budman, Cathy, Cath, Danielle, Cheon, Keun-Ah, Ciullo, Valentina, Coffey, Barbara J., Cusi, Daniele, Davis, Lea K., Denys, Damiaan, Depienne, Christel, Dietrich, Andrea, Eapen, Valsamma, Falkai, Peter, Fernandez, Thomas V., Garcia-Delgar, Blanca, Geller, Daniel A., Gilbert, Donald L., Grados, Marco A., Greenberg, Erica, Grünblatt, Edna, Hagstrøm, Julie, Hanna, Gregory L., Hartmann, Andreas, Hedderly, Tammy, Heiman, Gary A., Heyman, Isobel, Hong, Hyun Ju, Huang, Alden, Huyser, Chaim, Ibanez-Gomez, Laura, Khramtsova, Ekaterina A., Kim, Young Key, Kim, Young-Shin, King, Robert A., Koh, Yun-Joo, Konstantinidis, Anastasios, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett L., Lochner, Christine, Ludolph, Andrea G., Madruga-Garrido, Marcos, Malaty, Irene, Maras, Athanasios, McCracken, James T., Meijer, Inge A., Mir, Pablo, Morer, Astrid, Müller-Vahl, Kirsten R., Münchau, Alexander, Murphy, Tara L., Naarden, Allan, Nagy, Peter, Nestadt, Gerald, Nestadt, Paul S., Nicolini, Humberto, Nurmi, Erika L., Okun, Michael S., Paschou, Peristera, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Plessen, Kerstin J., Richter, Margaret A., Rizzo, Renata, Robertson, Mary, Roessner, Veit, Ruhrmann, Stephan, Samuels, Jack F., Sandor, Paul, Schlögelhofer, Monika, Shin, Eun-Young, Singer, Harvey, Song, Dong-Ho, Song, Jungeun, Spalletta, Gianfranco, Stein, Dan J., Stewart, S Evelyn, Storch, Eric A., Stranger, Barbara, Stuhrmann, Manfred, Tarnok, Zsanett, Tischfield, Jay A., Tübing, Jennifer, Visscher, Frank, Vulink, Nienke, Wagner, Michael, Walitza, Susanne, Wanderer, Sina, Woods, Martin, Worbe, Yulia, Zai, Gwyneth, Zinner, Samuel H., Sullivan, Patrick F., Franke, Barbara, Daly, Mark J., Bulik, Cynthia M., McIntosh, Andrew M., O’Donovan, Michael C., Zheutlin, Amanda, Andreassen, Ole A., Børglum, Anders D., Breen, Gerome, Edenberg, Howard J., Fanous, Ayman H., Faraone, Stephen V., Gelernter, Joel, Mathews, Carol A., Mattheisen, Manuel, Mitchell, Karen S., Neale, Michael C., Nurnberger, John I., Ripke, Stephan, Santangelo, Susan L., Scharf, Jeremiah M., Stein, Murray B., Thornton, Laura M., Walters, James T.R., Wray, Naomi R., Geschwind, Daniel H., Neale, Benjamin M., Kendler, Kenneth S., and Smoller, Jordan W.

Published
2019
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17. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author

O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Parikshak, Neelroop N, Newhouse, Stephen, Ripke, Stephan, Neale, Benjamin M, Purcell, Shaun M, Posthuma, Danielle, Nurnberger, John I, Lee, S Hong, Faraone, Stephen V, Perlis, Roy H, Mowry, Bryan J, Thapar, Anita, Goddard, Michael E, Witte, John S, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan E, Asherson, Philip, Azevedo, Maria H, Backlund, Lena, Badner, Judith A, Bailey, Anthony J, Banaschewski, Tobias, Barchas, Jack D, Barnes, Michael R, Barrett, Thomas B, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayes, Monica, Bellivier, Frank, Bergen, Sarah E, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B, Black, Donald W, Blackwood, Douglas HR, Bloss, Cinnamon S, Boehnke, Michael, Boomsma, Dorret I, Breuer, Rene, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy G, Buitelaar, Jan K, Bunney, William E, Buxbaum, Joseph D, Byerley, William F, Byrne, Enda M, Caesar, Sian, Cahn, Wiepke, Cantor, Rita M, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Mattheisen, Manuel, Cloninger, C Robert, Collier, David A, Cook, Edwin H, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William H, Craig, David W, Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary J, Doyle, Alysa E, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard P, Edenberg, Howard J, Elia, Josephine, Ennis, Sean, Etain, Bruno, and Fanous, Ayman

Subjects
Human Genome, Brain Disorders, Serious Mental Illness, Schizophrenia, Genetics, Depression, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Brain, Databases, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Histones, Humans, Mental Disorders, Signal Transduction, Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Published
2015

18. Editors’ Best of 2023

Author

Novins, Douglas K., primary, Althoff, Robert R., additional, Brotman, Melissa A., additional, DelBello, Melissa P., additional, Doyle, Alysa E., additional, Fortuna, Lisa R., additional, Fristad, Mary A., additional, Middeldorp, Christel M., additional, Njoroge, Wanjikũ F.M., additional, Rogers, Cynthia E., additional, and Singh, Manpreet Kaur, additional

Published
2024
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19. A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

Author

Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Hinds, David A., Hromatka, Bethann S., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McIntyre, Matthew H., Mountain, Joanna L., Northover, Carrie A.M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Albayrak, Özgür, Anney, Richard J.L., Vasquez, Alejandro Arias, Arranz, Maria Jesús, Asherson, Philip, Banaschewski, Tobias, Banaschewski, Tobias J., Bau, Claiton, Biederman, Joseph, Mortensen, Preben Bo, Børglum, Anders, Buitelaar, Jan K., Casas, Miguel, Charach, Alice, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Soeren, Daly, Mark J., Demontis, Ditte, Dempfle, Astrid, Doyle, Alysa E., Ebstein, Richard P., Elia, Josephine, Faraone, Stephen V., Föcker, Manuel, Franke, Barbara, Freitag, Christine, Gelernter, Joel, Gill, Michael, Grevet, Eugenio, Haavik, Jan, Hakonarson, Hakon, Hawi, Ziarih, Hebebrand, Johannes, Herpertz-Dahlmann, Beate, Hervas, Amaia, Hinney, Anke, Hohmann, Sarah, Holmans, Peter, Hutz, Mara, Ickowitz, Abel, Johansson, Stefan, Kent, Lindsey, Kittel-Schneider, Sarah, Kranzler, Henry, Kuntsi, Jonna, Lambregts-Rommelse, Nanda, Langley, Kate, Lehmkuhl, Gerd, Lesch, Klaus-Peter, Loo, Sandra K., Martin, Joanna, McGough, James J., Medland, Sarah E., Meyer, Jobst, Mick, Eric, Middletion, Frank, Miranda, Ana, Mulas, Fernando, Mulligan, Aisling, Neale, Benjamin M., Nelson, Stan F., Nguyen, T. Trang, O’Donovan, Michael C., Oades, Robert D., Owen, Michael J., Palmason, Haukur, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Renner, Tobias J., Rhode, Luis, Ribasés, Marta, Rietschel, Marcella, Ripke, Stephan, Rivero, Olga, Roeyers, Herbert, Romanos, Marcel, Romanos, Jasmin, Mota, Nina Roth, Rothenberger, Aribert, Sánchez-Mora, Cristina, Schachar, Russell, Schäfer, Helmut, Scherag, André, Schimmelmann, Benno G., Sergeant, Joseph, Sinzig, Judith, Smalley, Susan L., Sonuga-Barke, Edmund J.S., Steinhausen, Hans-Christoph, Sullivan, Patrick F., Thapar, Anita, Thompsom, Margaret, Todorov, Alexandre, Waldman, Irwin, Walitza, Susanne, Walters, Raymond, Wang, Yufeng, Warnke, Andreas, Williams, Nigel, Witt, Stephanie H., Yang, Li, Zayats, Tetyana, Zhang-James, Yanli, Agerbo, Esben, Als, Thomas Damm, Bækved-Hansen, Marie, Belliveau, Rich, Børglum, Anders D., Bybjerg-Grauholm, Jonas, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Dalsgaard, Søren, Dumont, Ashley, Goldstein, Jacqueline, Grove, Jakob, Hansen, Christine S., Hauberg, Mads Engel, Hollegaard, Mads V., Hougaard, David M., Howrigan, Daniel P., Huang, Hailiang, Maller, Julian, Martin, Alicia R., Mattheisen, Manuel, Moran, Jennifer, Mors, Ole, Nordentoft, Merete, Pallesen, Jonatan, Palmer, Duncan S., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Poterba, Timothy, Poulsen, Jesper Buchhave, Robinson, Elise B., Satterstrom, F. Kyle, Stevens, Christine, Turley, Patrick, Walters, Raymond K., Werge, Thomas, Lee, S. Hong, Robinson, Elise, Brikell, Isabell, Ghirardi, Laura, Larsson, Henrik, Lichtenstein, Paul, Eriksson, Nicholas, and Wray, Naomi R.

Published
2018
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21. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

Author

Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan, Asherson, Philip, Azevedo, Maria, Backlund, Lena, Badner, Judith, Bailey, Anthony, Banaschewski, Tobias, Barchas, Jack, Barnes, Michael, Barrett, Thomas, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayés, Mònica, Bellivier, Frank, Bergen, Sarah, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth, Black, Donald, Blackwood, Douglas, Boehnke, Michael, Boomsma, Dorret, Breen, Gerome, Breuer, René, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy, Buitelaar, Jan, Bunney, William, Buxbaum, Joseph, Byerley, William, Byrne, Enda, Caesar, Sian, Cahn, Wiepke, Cantor, Rita, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Cloninger, C, Collier, David, Cook, Edwin, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William, Craig, David, Craig, Ian, Crosbie, Jennifer, Cuccaro, Michael, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary, Doyle, Alysa, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard, Edenberg, Howard, Elia, Josephine, Ennis, Sean, Etain, Bruno, Fanous, Ayman, Farmer, Anne, Ferrier, I, Flickinger, Matthew, Fombonne, Eric, Foroud, Tatiana, Frank, Josef, Franke, Barbara, Fraser, Christine, Freedman, Robert, Giegling, Ina, Gill, Michael, Gordon, Scott, Gordon-Smith, Katherine, Green, Elaine, Greenwood, Tiffany, Grice, Dorothy, Gross, Magdalena, Grozeva, Detelina, and Guan, Weihua

Subjects
Adult, Attention Deficit Disorder with Hyperactivity, Bipolar Disorder, Child, Child Development Disorders, Pervasive, Crohn Disease, Depressive Disorder, Major, Genetic Heterogeneity, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Inheritance Patterns, Mental Disorders, Polymorphism, Single Nucleotide, Schizophrenia
Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohns disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Published
2013

22. High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression

Author

Hamshere, Marian L, Langley, Kate, Martin, Joanna, Agha, Sharifah Shameem, Stergiakouli, Evangelia, Anney, Richard JL, Buitelaar, Jan, Faraone, Stephen V, Lesch, Klaus-Peter, Neale, Benjamin M, Franke, Barbara, Sonuga-Barke, Edmund, Asherson, Philip, Merwood, Andrew, Kuntsi, Jonna, Medland, Sarah E, Ripke, Stephan, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J, Romanos, Marcel, Romanos, Jasmin, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Roeyers, Herbert, Biederman, Joseph, Doyle, Alysa E, Hakonarson, Hakon, Rothenberger, Aribert, Banaschewski, Tobias, Oades, Robert D, McGough, James J, Kent, Lindsey, Williams, Nigel, Owen, Michael J, Holmans, Peter, O’Donovan, Michael C, and Thapar, Anita

Subjects
Prevention, Behavioral and Social Science, Human Genome, Genetics, Mental Health, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Brain Disorders, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Mental health, Aggression, Anxiety Disorders, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Comorbidity, Conduct Disorder, Depressive Disorder, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Multifactorial Inheritance, United Kingdom, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.

Published
2013

26. Evidence for Genetic Association of RORB with Bipolar Disorder

Author

McGrath, Casey L, Glatt, Stephen J, Sklar, Pamela, Le-Niculescu, Helen, Kuczenski, Ronald, Doyle, Alysa E, Biederman, Joseph, Mick, Eric, Faraone, Stephen V, Niculescu, Alexander B, and Tsuang, Ming T

Abstract

Abstract Background Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA) and beta (RORB), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs) in RORA and RORB. Methods We genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching. Results We report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs. Conclusion Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder.

Published
2009

27. Editors’ Note: Third Annual Report Regarding JAACAP’s Antiracist Journey

Author

Novins, Douglas K., primary, Singh, Manpreet K., additional, Althoff, Robert R., additional, Bagot, Kara S., additional, Brotman, Melissa A., additional, DelBello, Melissa P., additional, Dickstein, Daniel P., additional, Doyle, Alysa E., additional, Drury, Stacy S., additional, Findling, Robert L., additional, Fortuna, Lisa R., additional, Fristad, Mary A., additional, Middeldorp, Christel M., additional, Njoroge, Wanjikũ F.M., additional, Rogers, Cynthia E., additional, Pumariega, Andrés J., additional, Bath, Eraka, additional, Tobón, Amalia Londoño, additional, Thompson-Felix, Tara, additional, and Billingsley, Mary K., additional

Published
2023
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32. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Author

Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Joanna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Havdahl, Alexandra, Doyle, Alysa, Reif, Andreas, Thapar, Anita, Cormand, Bru, Liao, Calwing, Burton, Christie, Bau, Claiton H. D., Rovaris, Diego Luiz, Sonuga-Barke, Edmund, Corfield, Elizabeth, Grevet, Eugenio Horacio, Larsson, Henrik, Gizer, Ian R., Waldman, Irwin, Brikell, Isabell, Haavik, Jan, Crosbie, Jennifer, McGough, James, Kuntsi, Jonna, Glessner, Joseph, Langley, Kate, Lesch, Klaus-Peter, Rohde, Luis Augusto, Hutz, Mara H., Klein, Marieke, Bellgrove, Mark, Tesli, Martin, O’Donovan, Michael C., Andreassen, Ole Andreas, Leung, Patrick W. L., Pan, Pedro M., Joober, Ridha, Schachar, Russel, Loo, Sandra, Witt, Stephanie H., Reichborn-Kjennerud, Ted, Banaschewski, Tobias, Hawi, Ziarih, Daly, Mark J., Mors, Ole, Nordentoft, Merete, Hougaard, David M., Mortensen, Preben Bo, Faraone, Stephen V., Stefansson, Hreinn, Roussos, Panos, Franke, Barbara, Werge, Thomas, Neale, Benjamin M., Stefansson, Kari, Børglum, Anders D., APH - Methodology, APH - Mental Health, Amsterdam Reproduction & Development, and Biological Psychology

Subjects
Cognition, All institutes and research themes of the Radboud University Medical Center, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], SDG 3 - Good Health and Well-being, Genetics, Brain, Humans, Genetic Predisposition to Disease, Attention Deficit Disorder with Hyperactivity/genetics, Genome-Wide Association Study
Abstract

Contains fulltext : 290804.pdf (Publisher’s version ) (Closed access) Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention. 01 februari 2023

Published
2023
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35. Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development

Author

Hughes, Dylan E., Kunitoki, Keiko, Elyounssi, Safia, Luo, Mannan, Bazer, Oren M., Hopkinson, Casey E., Dowling, Kevin F., Doyle, Alysa E., Dunn, Erin C., Eryilmaz, Hamdi, Gilman, Jodi M., Holt, Daphne J., Valera, Eve M., Smoller, Jordan W., Cecil, Charlotte A.M., Tiemeier, Henning, Lee, Phil H., Roffman, Joshua L., Hughes, Dylan E., Kunitoki, Keiko, Elyounssi, Safia, Luo, Mannan, Bazer, Oren M., Hopkinson, Casey E., Dowling, Kevin F., Doyle, Alysa E., Dunn, Erin C., Eryilmaz, Hamdi, Gilman, Jodi M., Holt, Daphne J., Valera, Eve M., Smoller, Jordan W., Cecil, Charlotte A.M., Tiemeier, Henning, Lee, Phil H., and Roffman, Joshua L.

Abstract

Childhood psychiatric symptoms are often diffuse but can coalesce into discrete mental illnesses during late adolescence. We leveraged polygenic scores (PGSs) to parse genomic risk for childhood symptoms and to uncover related neurodevelopmental mechanisms with transcriptomic and neuroimaging data. In independent samples (Adolescent Brain Cognitive Development, Generation R) a narrow cross-disorder neurodevelopmental PGS, reflecting risk for attention deficit hyperactivity disorder, autism, depression and Tourette syndrome, predicted psychiatric symptoms through early adolescence with greater sensitivity than broad cross-disorder PGSs reflecting shared risk across eight psychiatric disorders, the disorder-specific PGS individually or two other narrow cross-disorder (Compulsive, Mood-Psychotic) scores. Neurodevelopmental PGS-associated genes were preferentially expressed in the cerebellum, where their expression peaked prenatally. Further, lower gray matter volumes in cerebellum and functionally coupled cortical regions associated with psychiatric symptoms in mid-childhood. These findings demonstrate that the genetic underpinnings of pediatric psychiatric symptoms differ from those of adult illness, and implicate fetal cerebellar developmental processes that endure through childhood.

Published
2023

36. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains:[Inkl. Correction]

Author

Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Joanna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Havdahl, Alexandra, Doyle, Alysa, Reif, Andreas, Thapar, Anita, Cormand, Bru, Liao, Calwing, Burton, Christie, Bau, Claiton H.D., Rovaris, Diego Luiz, Sonuga-Barke, Edmund, Corfield, Elizabeth, Grevet, Eugenio Horacio, Larsson, Henrik, Gizer, Ian R., Nordentoft, Merete, Werge, Thomas, Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Joanna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Havdahl, Alexandra, Doyle, Alysa, Reif, Andreas, Thapar, Anita, Cormand, Bru, Liao, Calwing, Burton, Christie, Bau, Claiton H.D., Rovaris, Diego Luiz, Sonuga-Barke, Edmund, Corfield, Elizabeth, Grevet, Eugenio Horacio, Larsson, Henrik, Gizer, Ian R., Nordentoft, Merete, and Werge, Thomas

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84–98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

Published
2023

37. Polygenic Variation Underlying Educational Attainment and Attention-Deficit/Hyperactivity Disorder Indexes Behavior Ratings of Executive Functions in Child Psychiatry Outpatients.

Author

Capawana, Michael R., Vuijk, Pieter J., Martin, Joanna, Pollastri, Alisha R., Forchelli, Gina A., Woscoboinik, Georgia G., Tremblay, Sonia L., Wolfe, Lauren E., Braaten, Ellen B., and Doyle, Alysa E.

Subjects
EXECUTIVE function, EDUCATIONAL attainment, ATTENTION-deficit hyperactivity disorder, CHILD psychiatry, BEHAVIOR disorders, SPECIAL education teachers
Abstract

Objective: We leveraged common genetic variation underlying ADHD, educational attainment (EA) and cognition (COG) to understand the nature of the Behavior Rating Inventory for Executive Functions (BRIEF) and its relationship to academic functioning. Method: Participants were 991 youth, ages 7 to 17, consecutively referred for neuropsychiatric evaluation. Polygenic scores (PGS) for ADHD, EA, and COG were related to the BRIEF using regression analyses. Structural equation models were used to examine the associations between the PGS, BRIEF and academic outcomes (math, reading, and special education services [EDPLAN]). Results: After modeling the PGS together, only the EA and ADHD PGS significantly associated with the BRIEF. The BRIEF partially mediated the relationships between EA PGS with math and EDPLAN and fully mediated the relationship between ADHD PGS and EDPLAN. Conclusion: Genetic data extend evidence that the BRIEF measures a construct relevant to educational success that differs from what is indexed by cognitive testing. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development

Author

Hughes, Dylan E., primary, Kunitoki, Keiko, additional, Elyounssi, Safia, additional, Luo, Mannan, additional, Bazer, Oren M., additional, Hopkinson, Casey E., additional, Dowling, Kevin F., additional, Doyle, Alysa E., additional, Dunn, Erin C., additional, Eryilmaz, Hamdi, additional, Gilman, Jodi M., additional, Holt, Daphne J., additional, Valera, Eve M., additional, Smoller, Jordan W., additional, Cecil, Charlotte A. M., additional, Tiemeier, Henning, additional, Lee, Phil H., additional, and Roffman, Joshua L., additional

Published
2023
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39. Editors’ Best of 2024

Author

Novins, Douglas K., Althoff, Robert R., Brotman, Melissa A., DelBello, Melissa P., Doyle, Alysa E., Fortuna, Lisa R., Fristad, Mary A., Middeldorp, Christel M., Njoroge, Wanjikũ F.M., Rogers, Cynthia E., and Singh, Manpreet Kaur

Published
2025
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40. Uncovering and mitigating bias in large, automated MRI analyses of brain development

Author

Elyounssi, Safia, primary, Kunitoki, Keiko, additional, Clauss, Jacqueline A., additional, Laurent, Eline, additional, Kane, Kristina, additional, Hughes, Dylan E., additional, Hopkinson, Casey E., additional, Bazer, Oren, additional, Sussman, Rachel Freed, additional, Doyle, Alysa E., additional, Lee, Hang, additional, Tervo-Clemmens, Brenden, additional, Eryilmaz, Hamdi, additional, Gollub, Randy L., additional, Barch, Deanna M., additional, Satterthwaite, Theodore D., additional, Dowling, Kevin F., additional, and Roffman, Joshua L., additional

Published
2023
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41. Editors’ Best of 2022

Author

Novins, Douglas K., primary, Althoff, Robert R., additional, Brotman, Melissa A., additional, Cortese, Samuele, additional, DelBello, Melissa, additional, Doyle, Alysa, additional, Drury, Stacy S., additional, Fortuna, Lisa, additional, Frazier, Jean A., additional, Fristad, Mary, additional, Henderson, Schuyler W., additional, McCauley, Elizabeth, additional, Middeldorp, Christel, additional, Njoroge, Wanjikũ F.M., additional, Rogers, Cynthia E., additional, and White, Tonya, additional

Published
2023
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44. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

Author

Loo, Sandra K., Shtir, Corina, and Doyle, Alysa E.

Abstract

Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally homogeneous family sample of 656 individuals with at least one child affected by attention-deficit/hyperactivity disorder (ADHD). Results: Haplotype trend regression analysis with sliding four-SNP windows identified haplotypes of genome-wide significance in genes involved in synaptic signaling ("KIF16B"; p = 1.27E-08) and neurodevelopment ("PAX5"; p = 3.58E-08), and highlight findings from a recent genetic study of cognitive ability ("RXRA"; p = 7.7E-08; "GYPC"; p = 2.5E-07). Further interrogation of SNPs within top haplotypes reveals that the minor alleles are associated with higher intelligence, whereas others are associated with relatively lower (but still average range) intelligence. Effects of the eight genes are additive, as a greater number of the associated genotypes in a given individual predict higher intelligence (p = 5.36E-08) and account for 8% of variance in intelligence. Conclusions: Analyses that examine additive genetic effects may be useful in identifying regions where the additive effects of SNPs have a significant effect on phenotype. These results describe novel variants and additive effects of genes involved in brain development on variability in intelligence within an ADHD sample. The precise mechanisms of these loci in relation to determining individual differences in general cognitive ability require further investigation. (Contains 3 tables and 3 figures.)

Published
2012
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45. Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Author

Kong, Xiang-Zhen, Francks, Clyde, Allen, Nicholas B., Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C., Hoekstra, Pieter J., Holst, Ruth J., Hoogman, Martine, Høvik, Marie F., Howells, Fleur M., Ames, David, Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L., Jönsson, Erik G, Kaleda, Vasily, Kelly, Clare, Andreassen, Ole A., Kerich, Michael, Keshavan, Matcheri S., Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Krämer, Bernd, Krug, Axel, Kuntsi, Jonna, Vasquez, Alejandro Arias, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Lim, Kelvin O., Liu, Jia, Armstrong, Nicola J., Lochner, Christine, London, Edythe D., Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J., Mackey, Scott, MacMaster, Frank P., Maingault, Sophie, Malpas, Charles B., Asherson, Phil, Malt, Ulrik F., Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R., McCarthy, Hazel, Medland, Sarah, Metha, Mitul, Mitchell, Philip B., Mueller, Bryon A., Maniega, Susana Muñoz, Bergo, Felipe, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L., McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M., Narayanaswamy, Janardhanan C., Moreira, José Carlos Vasques, Nerland, Stener, Bastin, Mark E., Nestor, Liam, Newman, Erik, Nigg, Joel T., Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L., Oosterlaan, Jaap, Oranje, Bob, Orr, Catherine, Batalla, Albert, Overs, Bronwyn, Paloyelis, Yannis, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, Polier, Georg G., Pomarol-Clotet, Edith, Portella, Maria J., Qiu, Jiang, Radua, Joaquim, Bauer, Jochen, Ramos-Quiroga, Josep Antoni, Reddy, Y. C. Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Schmaal, Lianne, Baune, Bernhard T, Schulte-Rüther, Martin, Schweren, Lizanne, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J., Simmons, Alan N., Simulionyte, Egle, Sinha, Rajita, Baur-Streubel, Ramona, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R., Stein, Dan J., Stein, Elliot A., Stevens, Michael, Strike, Lachlan T., Biederman, Joseph, Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S., Thoma, Robert J., Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Erp, Theo G. M., Blaine, Sara K., Heuvel, Odile A., Meer, Dennis, Eijk, Liza, Vance, Alasdair, Veer, Ilya M., Veltman, Dick J., Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Voineskos, Aristotle N, Boedhoe, Premika, Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., White, Tonya, Bøen, Erlend, Wiers, Reinout W., Wright, Margaret J., Wittfeld, Katharina, Yang, Tony T., Yasuda, Clarissa L., Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Zhen, Zonglei, Bose, Anushree, Zhu, Xing-xing, Ziegler, Georg C., Zubicaray, Greig I., Zwiers, Marcel, Project, Karolinska Schizophrenia, Glahn, David C., Crivello, Fabrice, Fisher, Simon E., Thompson, Paul M., Bralten, Janita, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Collste, Karin, Brandeis, Daniel, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl, Brem, Silvia, Mathias, Samuel R., Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J., Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Cannon, Dara M., Guadalupe, Tulio, Caparelli, Elisabeth C., Castellanos, Francisco X., Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P., Abé, Christoph, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, Bruttopilo, Sara Ambrosino, Zeeuw, Patrick, Deary, Ian J., Demeter, Damion V., Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, Nhat Trung, Doherty, Colin P., Doyle, Alysa, Durston, Sarah, Earl, Eric, Akudjedu, Theophilus N., Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N., Fair, Damien A., Faraone, Stephen V., Fernández, Guillén, Flint, Claas, Filho, Geraldo Busatto, Förster, Katharina, Aleman, Andre, Fouche, Jean-Paul, Foxe, John J., Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice M., Garavan, Hugh, Santos Garcia, Danielle, Gotlib, Ian H., Goudriaan, Anna E., Grabe, Hans Jörgen, Alhusaini, Saud, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K., Harris, Mathew A., Hartman, Catharina A., Carmen Valdés Hernández, Maria, Alhusaini, Saud, Del Carmen Valdés Hernández, Maria, Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C., Hoekstra, Pieter J., van Holst, Ruth J., Hoogman, Martine, Høvik, Marie F., Allen, Nicholas B., Howells, Fleur M., Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L., Jönsson, Erik G., Kaleda, Vasily, Ames, David, Kelly, Clare, Kerich, Michael, Keshavan, Matcheri S., Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Krämer, Bernd, Krug, Axel, Andreassen, Ole A., Kuntsi, Jonna, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Lim, Kelvin O., Vasquez, Alejandro Arias, Liu, Jia, Lochner, Christine, London, Edythe D., Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J., Mackey, Scott, MacMaster, Frank P., Maingault, Sophie, Armstrong, Nicola J., Malpas, Charles B., Malt, Ulrik F., Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R., McCarthy, Hazel, Medland, Sarah, Metha, Mitul, Mitchell, Philip B., Mueller, Bryon A., Asherson, Phil, Maniega, Susana Muñoz, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L., McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M., Narayanaswamy, Janardhanan C., Moreira, José Carlos Vasques, Bergo, Felipe, Nerland, Stener, Nestor, Liam, Newman, Erik, Nigg, Joel T., Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L., Oosterlaan, Jaap, Oranje, Bob, Bastin, Mark E., Orr, Catherine, Overs, Bronwyn, Paloyelis, Yannis, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, von Polier, Georg G., Pomarol-Clotet, Edith, Portella, Maria J., Qiu, Jiang, Batalla, Albert, Radua, Joaquim, Ramos-Quiroga, Josep Antoni, Reddy, Y. C. Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Bauer, Jochen, Schmaal, Lianne, Schulte-Rüther, Martin, Schweren, Lizanne, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J., Simmons, Alan N., Simulionyte, Egle, Baune, Bernhard T., Sinha, Rajita, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R., Stein, Dan J., Stein, Elliot A., Stevens, Michael, Baur-Streubel, Ramona, Strike, Lachlan T., Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S., Thoma, Robert J., Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Biederman, Joseph, van Erp, Theo G. M., van den Heuvel, Odile A., van der Meer, Dennis, van Eijk, Liza, Vance, Alasdair, Veer, Ilya M., Veltman, Dick J., Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Blaine, Sara K., Voineskos, Aristotle N., Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Boedhoe, Premika, White, Tonya, Wiers, Reinout W., Wright, Margaret J., Wittfeld, Katharina, Yang, Tony T., Yasuda, Clarissa L., Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Bøen, Erlend, Zhen, Zonglei, Zhu, Xing-Xing, Ziegler, Georg C., de Zubicaray, Greig I., Zwiers, Marcel, Project, Karolinska Schizophrenia, Glahn, David C., Crivello, Fabrice, Fisher, Simon E., Thompson, Paul M., Bose, Anushree, Francks, Clyde, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Bralten, Janita, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl, Brandeis, Daniel, Kong, Xiang-Zhen, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J., Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Mathias, Samuel R., Cannon, Dara M., Caparelli, Elisabeth C., Castellanos, Francisco X., Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-Lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Guadalupe, Tulio, Clark, Vincent P., Coghill, David, Connolly, Colm G., Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, de Bruttopilo, Sara Ambrosino, Abé, Christoph, de Zeeuw, Patrick, Deary, Ian J., Demeter, Damion V., Di Martino, Adriana, Dickie, Erin W., Dietsche, Bruno, Doan, Nhat Trung, Doherty, Colin P., Doyle, Alysa, Durston, Sarah, Earl, Eric, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N., Fair, Damien A., Faraone, Stephen V., Fernández, Guillén, Flint, Claas, Filho, Geraldo Busatto, Akudjedu, Theophilus N., Förster, Katharina, Fouche, Jean-Paul, Foxe, John J., Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice M., Garavan, Hugh, do Santos Garcia, Danielle, Gotlib, Ian H., Goudriaan, Anna E., Aleman, Andre, Grabe, Hans Jörgen, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K., Harris, Mathew A., Hartman, Catharina A., Ontwikkelingspsychologie (Psychologie, FMG), Adult Psychiatry, APH - Mental Health, ANS - Compulsivity, Impulsivity & Attention, Child and Adolescent Psychiatry & Psychosocial Care, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, Laboratory Genetic Metabolic Diseases, Paediatrics, General Paediatrics, ARD - Amsterdam Reproduction and Development, Paediatric Pulmonology, Graduate School, and APH - Digital Health

Subjects
P‐hacking, Datasets as Topic, Publication bias, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, Statistics, team science, Brain asymmetry, Multicenter Studies as Topic, Cervell, Research Articles, Cerebral Cortex, Radiological and Ultrasound Technology, P-hacking, 05 social sciences, Brain, Cerebral cortex, Middle Aged, Magnetic Resonance Imaging, Discoveries in science, Escorça cerebral, Neurology, Biaix de publicació, Anatomy, Psychology, Research Article, Neuroinformatics, Adult, Adolescent, Neuroimaging, Descobriments científics, 050105 experimental psychology, Statistical power, 03 medical and health sciences, Young Adult, Magnetic resonance imaging, Imatges per ressonància magnètica, multisite collaboration, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, reproducibility, Aged, publication bias, Reproducibility, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Perspective (graphical), Reproducibility of Results, Brain Cortical Thickness, Research data, Sample size determination, Dades de recerca, Neurology (clinical), Scale (map), Developmental Psychopathology, 030217 neurology & neurosurgery
Abstract

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes., Region‐wise effect sizes and reproducibility rates of hemispheric asymmetry effects. In general, effects with higher effect sizes showed higher reproducibility, given the same conditions (e.g., sample size and data heterogeneity).

Published
2022
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46. Genome-Wide Association Study of the Child Behavior Checklist Dysregulation Profile

Author

Mick, Eric, McGough, James, Loo, Sandra, Doyle, Alysa E., Wozniak, Janet, Wilens, Timothy E., Smalley, Susan, McCracken, James, Biederman, Joseph, and Faraone, Stephen V.

Abstract

Objective: A potentially useful tool for understanding the distribution and determinants of emotional dysregulation in children is a Child Behavior Checklist profile, comprising the Attention Problems, Anxious/Depressed, and Aggressive Behavior clinical subscales (CBCL-DP). The CBCL-DP indexes a heritable trait that increases susceptibility for later psychopathology, including severe mood problems and aggressive behavior. We have conducted a genome-wide association study of the CBCL-DP in children with attention-deficit/hyperactivity disorder (ADHD). Method: Families were ascertained at Massachusetts General Hospital and University of California, Los Angeles. Genotyping was conducted with the Illumina Human1M or Human1M-Duo BeadChip platforms. Genome-wide association analyses were conducted with the MQFAM multivariate extension of PLINK. Results: CBCL data were available for 341 ADHD offspring from 339 ADHD affected trio families from the UCLA (N = 128) and the MGH (N = 213) sites. We found no genome-wide statistically significant associations but identified several plausible candidate genes among findings at p less than 5E-05: "TMEM132D," "LRRC7," "SEMA3A," "ALK," and "STIP1" Conclusions: We found suggestive evidence for developmentally expressed genes operant in hippocampal dependent memory and learning with the CBCL-DP. (Contains 2 figures and 3 tables.)

Published
2011
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50. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

Author

Neale, Benjamin M., Medland, Sarah E., Ripke, Stephan, Asherson, Philip, Franke, Barbara, Lesch, Klaus-Peter, Faraone, Stephen V., Nguyen, Thuy Trang, Schafer, Helmut, Holmans, Peter, Daly, Mark, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J., Romanos, Marcel, Romanos, Jasmin, Walitza, Susanne, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Buitelaar, Jan, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Gill, Michael, Anney, Richard J. L., Langely, Kate, O'Donovan, Michael, Williams, Nigel, Owen, Michael, Thapar, Anita, Kent, Lindsey, Sergeant, Joseph, Roeyers, Herbert, Mick, Eric, Biederman, Joseph, Doyle, Alysa, Smalley, Susan, Loo, Sandra, Hakonarson, Hakon, Elia, Josephine, Todorov, Alexandre, Miranda, Ana, Mulas, Fernando, Ebstein, Richard P., Rothenberger, Aribert, Banaschewski, Tobias, Oades, Robert D., Sonuga-Barke, Edmund, McGough, James, Nisenbaum, Laura, Middleton, Frank, Hu, Xiaolan, and Nelson, Stan

Abstract

Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. Method: We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. Results: No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. Conclusions: Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability. (Contains 3 figures and 3 tables.)

Published
2010
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