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2. Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses.

Author

Banaj, Nerisa, Vecchio, Daniela, Piras, Fabrizio, De Rossi, Pietro, Bustillo, Juan, Ciufolini, Simone, Dazzan, Paola, Di Forti, Marta, Dickie, Erin, Ford, Judith, Fuentes-Claramonte, Paola, Gruber, Oliver, Guerrero-Pedraza, Amalia, Hamilton, Holly, Howells, Fleur, Kraemer, Bernd, Lawrie, Stephen, Radua, Joaquim, Richter, Anja, Salvador, Raymond, Sawa, Akira, Scheffler, Freda, Sim, Kang, Spaniel, Filip, Stein, Dan, Temmingh, Henk, Thomopoulos, Sophia, Tomecek, David, Uhlmann, Anne, Voineskos, Aristotle, Yang, Kun, Jahanshad, Neda, Thompson, Paul, Murray, Robin, Pomarol-Clotet, Edith, Turner, Jessica, Spalletta, Gianfranco, Piras, Federica, Mathalon, Daniel, Potkin, Steven, Van Erp, Theodorus, and Preda, Adrian

Subjects
Humans, Schizophrenia, Magnetic Resonance Imaging, Neuroimaging, Parietal Lobe, Syndrome, Cerebral Cortex
Abstract

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Published
2023

6. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

Satizabal, Claudia L, Adams, Hieab HH, Hibar, Derrek P, White, Charles C, Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, and Schmidt, Helena

Subjects
Biological Sciences, Genetics, Mental Health, Human Genome, Neurosciences, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Animals, Brain, Cohort Studies, Drosophila melanogaster, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders, Organ Size, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019

8. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.

Author

van Erp, Theo GM, Walton, Esther, Hibar, Derrek P, Schmaal, Lianne, Jiang, Wenhao, Glahn, David C, Pearlson, Godfrey D, Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Bustillo, Juan R, Clark, Vincent P, Agartz, Ingrid, Mueller, Bryon A, Cahn, Wiepke, de Zwarte, Sonja MC, Hulshoff Pol, Hilleke E, Kahn, René S, Ophoff, Roel A, van Haren, Neeltje EM, Andreassen, Ole A, Dale, Anders M, Doan, Nhat Trung, Gurholt, Tiril P, Hartberg, Cecilie B, Haukvik, Unn K, Jørgensen, Kjetil N, Lagerberg, Trine V, Melle, Ingrid, Westlye, Lars T, Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Zilles, David, Calhoun, Vince D, Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Carr, Vaughan J, Catts, Stanley, Cropley, Vanessa L, Fullerton, Janice M, Green, Melissa J, Henskens, Frans A, Jablensky, Assen, Lenroot, Rhoshel K, Mowry, Bryan J, Michie, Patricia T, Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J, Cairns, Murray J, Seal, Marc, Tooney, Paul A, Rasser, Paul E, Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W, Morris, Derek W, Hong, Elliot, Kochunov, Peter, Beard, Lauren M, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, Belger, Aysenil, Brown, Gregory G, Ford, Judith M, Macciardi, Fabio, Mathalon, Daniel H, O'Leary, Daniel S, Potkin, Steven G, Preda, Adrian, Voyvodic, James, Lim, Kelvin O, McEwen, Sarah, Yang, Fude, Tan, Yunlong, Tan, Shuping, Wang, Zhiren, Fan, Fengmei, Chen, Jingxu, Xiang, Hong, Tang, Shiyou, Guo, Hua, Wan, Ping, Wei, Dong, Bockholt, Henry J, Ehrlich, Stefan, Wolthusen, Rick PF, King, Margaret D, Shoemaker, Jody M, Sponheim, Scott R, De Haan, Lieuwe, and Koenders, Laura

Subjects
Karolinska Schizophrenia Project, Brain, Frontal Lobe, Prefrontal Cortex, Temporal Lobe, Humans, Magnetic Resonance Imaging, Severity of Illness Index, Linear Models, Case-Control Studies, Schizophrenia, Age of Onset, Adolescent, Adult, Aged, Middle Aged, Child, Female, Male, Young Adult, Neuroimaging, Cortical, Imaging, Meta-analysis, Surface area, Thickness, Serious Mental Illness, Biomedical Imaging, Mental Health, Clinical Research, Neurosciences, Brain Disorders, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundThe profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.MethodsThe study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.ResultsCompared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.ConclusionsThe findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Published
2018

9. A Reference Architecture for Smart Digital Platform for Personalized Prevention and Patient Management

Author

Elgammal, Amal, Krämer, Bernd J., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Aiello, Marco, editor, Bouguettaya, Athman, editor, Tamburri, Damian Andrew, editor, and van den Heuvel, Willem-Jan, editor

Published
2021
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10. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex.

Author

Guadalupe, Tulio, Mathias, Samuel R, vanErp, Theo GM, Whelan, Christopher D, Zwiers, Marcel P, Abe, Yoshinari, Abramovic, Lucija, Agartz, Ingrid, Andreassen, Ole A, Arias-Vásquez, Alejandro, Aribisala, Benjamin S, Armstrong, Nicola J, Arolt, Volker, Artiges, Eric, Ayesa-Arriola, Rosa, Baboyan, Vatche G, Banaschewski, Tobias, Barker, Gareth, Bastin, Mark E, Baune, Bernhard T, Blangero, John, Bokde, Arun LW, Boedhoe, Premika SW, Bose, Anushree, Brem, Silvia, Brodaty, Henry, Bromberg, Uli, Brooks, Samantha, Büchel, Christian, Buitelaar, Jan, Calhoun, Vince D, Cannon, Dara M, Cattrell, Anna, Cheng, Yuqi, Conrod, Patricia J, Conzelmann, Annette, Corvin, Aiden, Crespo-Facorro, Benedicto, Crivello, Fabrice, Dannlowski, Udo, de Zubicaray, Greig I, de Zwarte, Sonja MC, Deary, Ian J, Desrivières, Sylvane, Doan, Nhat Trung, Donohoe, Gary, Dørum, Erlend S, Ehrlich, Stefan, Espeseth, Thomas, Fernández, Guillén, Flor, Herta, Fouche, Jean-Paul, Frouin, Vincent, Fukunaga, Masaki, Gallinat, Jürgen, Garavan, Hugh, Gill, Michael, Suarez, Andrea Gonzalez, Gowland, Penny, Grabe, Hans J, Grotegerd, Dominik, Gruber, Oliver, Hagenaars, Saskia, Hashimoto, Ryota, Hauser, Tobias U, Heinz, Andreas, Hibar, Derrek P, Hoekstra, Pieter J, Hoogman, Martine, Howells, Fleur M, Hu, Hao, Hulshoff Pol, Hilleke E, Huyser, Chaim, Ittermann, Bernd, Jahanshad, Neda, Jönsson, Erik G, Jurk, Sarah, Kahn, Rene S, Kelly, Sinead, Kraemer, Bernd, Kugel, Harald, Kwon, Jun Soo, Lemaitre, Herve, Lesch, Klaus-Peter, Lochner, Christine, Luciano, Michelle, Marquand, Andre F, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Martinot, Jean-Luc, Mataix-Cols, David, Mather, Karen, McDonald, Colm, McMahon, Katie L, Medland, Sarah E, Menchón, José M, Morris, Derek W, Mothersill, Omar, Maniega, Susana Munoz, and Mwangi, Benson

Subjects
Brain, Humans, Magnetic Resonance Imaging, Organ Size, Aging, Sex Characteristics, Quantitative Trait, Heritable, Adolescent, Adult, Aged, Middle Aged, Female, Male, Functional Laterality, Meta-Analysis as Topic, Young Adult, Age, Enigma, Handedness, Heritability, Meta-analysis, Sex, Subcortical brain asymmetry, Quantitative Trait, Heritable, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology
Abstract

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

Published
2017

13. Novel genetic loci associated with hippocampal volume.

Author

Hibar, Derrek P, Adams, Hieab HH, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher RK, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David CM, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, and Teumer, Alexander

Subjects
Hippocampus, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Protein-Serine-Threonine Kinases, Glycoproteins, Microtubule-Associated Proteins, Nerve Tissue Proteins, Organ Size, Cohort Studies, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Female, Male, Genome-Wide Association Study, Young Adult, Methionine Sulfoxide Reductases, Genetic Loci, Dipeptidyl Peptidase 4, Human Genome, Aging, Brain Disorders, Clinical Research, Acquired Cognitive Impairment, Neurodegenerative, Dementia, Neurosciences, Prevention, Genetics, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Mental Health, 2.1 Biological and endogenous factors, Mental health, Neurological
Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published
2017

14. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author

Adams, Hieab HH, Hibar, Derrek P, Chouraki, Vincent, Stein, Jason L, Nyquist, Paul A, Rentería, Miguel E, Trompet, Stella, Arias-Vasquez, Alejandro, Seshadri, Sudha, Desrivières, Sylvane, Beecham, Ashley H, Jahanshad, Neda, Wittfeld, Katharina, Van der Lee, Sven J, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beiser, Alexa, Bernard, Manon, Bis, Joshua C, Blanken, Laura ME, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chauhan, Ganesh, Chen, Qiang, Ching, Christopher RK, Cuellar-Partida, Gabriel, Braber, Anouk Den, Doan, Nhat Trung, Ehrlich, Stefan, Filippi, Irina, Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Greven, Corina U, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Hass, Johanna, Haukvik, Unn K, Hilal, Saima, Hofer, Edith, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liao, Jiemin, Liewald, David CM, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, Mazoyer, Bernard, McKay, David R, McWhirter, Rebekah, Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Muetzel, Ryan L, Maniega, Susana Muñoz, Nho, Kwangsik, Nugent, Allison C, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pappa, Irene, Pirpamer, Lukas, Pudas, Sara, Pütz, Benno, Rajan, Kumar B, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, and Satizabal, Claudia L

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Genetics, Aging, Clinical Research, Biotechnology, Neurodegenerative, Brain Disorders, Human Genome, Prevention, 2.1 Biological and endogenous factors, Brain, Cognition, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Oncogene Protein v-akt, Parkinson Disease, Phenotype, Phosphatidylinositol 3-Kinases, Polymorphism, Single Nucleotide, White People, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Published
2016

15. Common genetic variants influence human subcortical brain structures

Author

Hibar, Derrek P, Stein, Jason L, Renteria, Miguel E, Arias-Vasquez, Alejandro, Desrivières, Sylvane, Jahanshad, Neda, Toro, Roberto, Wittfeld, Katharina, Abramovic, Lucija, Andersson, Micael, Aribisala, Benjamin S, Armstrong, Nicola J, Bernard, Manon, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brown, Andrew A, Mallar Chakravarty, M, Chen, Qiang, Ching, Christopher RK, Cuellar-Partida, Gabriel, den Braber, Anouk, Giddaluru, Sudheer, Goldman, Aaron L, Grimm, Oliver, Guadalupe, Tulio, Hass, Johanna, Woldehawariat, Girma, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Olde Loohuis, Loes M, Luciano, Michelle, Macare, Christine, Mather, Karen A, Mattheisen, Manuel, Milaneschi, Yuri, Nho, Kwangsik, Papmeyer, Martina, Ramasamy, Adaikalavan, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rose, Emma J, Salami, Alireza, Sämann, Philipp G, Schmaal, Lianne, Schork, Andrew J, Shin, Jean, Strike, Lachlan T, Teumer, Alexander, van Donkelaar, Marjolein MJ, van Eijk, Kristel R, Walters, Raymond K, Westlye, Lars T, Whelan, Christopher D, Winkler, Anderson M, Zwiers, Marcel P, Alhusaini, Saud, Athanasiu, Lavinia, Ehrlich, Stefan, Hakobjan, Marina MH, Hartberg, Cecilie B, Haukvik, Unn K, Heister, Angelien JGAM, Hoehn, David, Kasperaviciute, Dalia, Liewald, David CM, Lopez, Lorna M, Makkinje, Remco RR, Matarin, Mar, Naber, Marlies AM, Reese McKay, D, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Royle, Natalie A, Shen, Li, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia SL, van Hulzen, Kimm JE, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, and Czisch, Michael

Subjects
Biological Psychology, Biological Sciences, Genetics, Psychology, Brain Disorders, Human Genome, Mental Health, Neurosciences, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Mental health, Adolescent, Adult, Aged, Aged, 80 and over, Aging, Apoptosis, Brain, Caudate Nucleus, Child, Female, Gene Expression Regulation, Developmental, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Membrane Proteins, Middle Aged, Organ Size, Putamen, Sex Characteristics, Skull, Young Adult, Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN, IMAGEN, SYS, General Science & Technology
Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Published
2015

16. The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

Author

de Zwarte, Sonja M.C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Aleman, André, Alpert, Kathryn I., Bearden, Carrie E., Bertolino, Alessandro, Bois, Catherine, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E.L., Cahn, Wiepke, Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Erk, Susanne, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Frankland, Andrew, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Goldman, Aaron L., Gonul, Ali Saffet, Gruber, Oliver, de Haan, Lieuwe, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hillegers, Manon H.J., Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M.G., Kopecek, Miloslav, Krabbendam, Lydia, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Marsman, Jan-Bernard C., Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Najt, Pablo, Neilson, Emma, Newport, Jason, van Os, Jim, Overs, Bronwyn, Ozerdem, Aysegul, Picchioni, Marco M., Richter, Anja, Roberts, Gloria, Aydogan, Aybala Saricicek, Schofield, Peter R., Simsek, Fatma, Soares, Jair C., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Walter, Henrik, Wang, Lei, Weinberger, Daniel R., Whalley, Heather C., Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R.K., van Erp, Theo G.M., Turner, Jessica A., Jahanshad, Neda, Thompson, Paul M., Kahn, René S., and van Haren, Neeltje E.M.

Published
2019
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18. Discovery

Author

Dustdar, Schahram, Platzer, Christian, Krämer, Bernd J., Jacobsen, H.-Arno, Section editor, Liu, Ling, editor, and Özsu, M. Tamer, editor

Published
2018
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19. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author

Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, van Erp, Theo G.M., Walton, Esther, Hibar, Derrek P., Schmaal, Lianne, Jiang, Wenhao, Glahn, David C., Pearlson, Godfrey D., Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Bustillo, Juan R., Clark, Vincent P., Mueller, Bryon A., Cahn, Wiepke, de Zwarte, Sonja M.C., Hulshoff Pol, Hilleke E., Kahn, René S., Ophoff, Roel A., van Haren, Neeltje E.M., Andreassen, Ole A., Dale, Anders M., Doan, Nhat Trung, Gurholt, Tiril P., Hartberg, Cecilie B., Haukvik, Unn K., Jørgensen, Kjetil N., Lagerberg, Trine V., Melle, Ingrid, Westlye, Lars T., Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Zilles, David, Calhoun, Vince D., Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Carr, Vaughan J., Catts, Stanley, Cropley, Vanessa L., Fullerton, Janice M., Green, Melissa J., Henskens, Frans A., Jablensky, Assen, Lenroot, Rhoshel K., Mowry, Bryan J., Michie, Patricia T., Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J., Cairns, Murray J., Seal, Marc, Tooney, Paul A., Rasser, Paul E., Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W., Morris, Derek W., Hong, Elliot, Kochunov, Peter, Beard, Lauren M., Gur, Raquel E., Gur, Ruben C., Satterthwaite, Theodore D., Wolf, Daniel H., Belger, Aysenil, Brown, Gregory G., Ford, Judith M., Macciardi, Fabio, Mathalon, Daniel H., O’Leary, Daniel S., Potkin, Steven G., Preda, Adrian, Voyvodic, James, Lim, Kelvin O., McEwen, Sarah, Yang, Fude, Tan, Yunlong, Tan, Shuping, Wang, Zhiren, Fan, Fengmei, Chen, Jingxu, Xiang, Hong, Tang, Shiyou, Guo, Hua, Wan, Ping, Wei, Dong, Bockholt, Henry J., Ehrlich, Stefan, Wolthusen, Rick P.F., King, Margaret D., Shoemaker, Jody M., Sponheim, Scott R., De Haan, Lieuwe, Koenders, Laura, Machielsen, Marise W., van Amelsvoort, Therese, Veltman, Dick J., Assogna, Francesca, Banaj, Nerisa, de Rossi, Pietro, Iorio, Mariangela, Piras, Fabrizio, Spalletta, Gianfranco, McKenna, Peter J., Pomarol-Clotet, Edith, Salvador, Raymond, Corvin, Aiden, Donohoe, Gary, Kelly, Sinead, Whelan, Christopher D., Dickie, Erin W., Rotenberg, David, Voineskos, Aristotle N., Ciufolini, Simone, Radua, Joaquim, Dazzan, Paola, Murray, Robin, Reis Marques, Tiago, Simmons, Andrew, Borgwardt, Stefan, Egloff, Laura, Harrisberger, Fabienne, Riecher-Rössler, Anita, Smieskova, Renata, Alpert, Kathryn I., Wang, Lei, Jönsson, Erik G., Koops, Sanne, Sommer, Iris E.C., Bertolino, Alessandro, Bonvino, Aurora, Di Giorgio, Annabella, Neilson, Emma, Mayer, Andrew R., Stephen, Julia M., Kwon, Jun Soo, Yun, Je-Yeon, Cannon, Dara M., McDonald, Colm, Lebedeva, Irina, Tomyshev, Alexander S., Akhadov, Tolibjohn, Kaleda, Vasily, Busatto, Geraldo F., Rosa, Pedro G.P., Serpa, Mauricio H., Zanetti, Marcus V., Hoschl, Cyril, Skoch, Antonin, Spaniel, Filip, Tomecek, David, Hagenaars, Saskia P., McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., Knöchel, Christian, Oertel-Knöchel, Viola, Stäblein, Michael, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Uhlmann, Anne, Lopez-Jaramillo, Carlos, Dima, Danai, McMahon, Agnes, Faskowitz, Joshua I., Gutman, Boris A., Jahanshad, Neda, Thompson, Paul M., and Turner, Jessica A.

Published
2018
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26. Discovery

Author

Dustdar, Schahram, Platzer, Christian, Krämer, Bernd J., LIU, LING, editor, and ÖZSU, M. TAMER, editor

Published
2009
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30. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Author

Guadalupe, Tulio, Mathias, Samuel R., vanErp, Theo G. M., Whelan, Christopher D., Zwiers, Marcel P., Abe, Yoshinari, Abramovic, Lucija, Agartz, Ingrid, Andreassen, Ole A., Arias-Vásquez, Alejandro, Aribisala, Benjamin S., Armstrong, Nicola J., Arolt, Volker, Artiges, Eric, Ayesa-Arriola, Rosa, Baboyan, Vatche G., Banaschewski, Tobias, Barker, Gareth, Bastin, Mark E., Baune, Bernhard T., Blangero, John, Bokde, Arun L.W., Boedhoe, Premika S.W., Bose, Anushree, Brem, Silvia, Brodaty, Henry, Bromberg, Uli, Brooks, Samantha, Büchel, Christian, Buitelaar, Jan, Calhoun, Vince D., Cannon, Dara M., Cattrell, Anna, Cheng, Yuqi, Conrod, Patricia J., Conzelmann, Annette, Corvin, Aiden, Crespo-Facorro, Benedicto, Crivello, Fabrice, Dannlowski, Udo, de Zubicaray, Greig I., de Zwarte, Sonja M.C., Deary, Ian J., Desrivières, Sylvane, Doan, Nhat Trung, Donohoe, Gary, Dørum, Erlend S., Ehrlich, Stefan, Espeseth, Thomas, Fernández, Guillén, Flor, Herta, Fouche, Jean-Paul, Frouin, Vincent, Fukunaga, Masaki, Gallinat, Jürgen, Garavan, Hugh, Gill, Michael, Suarez, Andrea Gonzalez, Gowland, Penny, Grabe, Hans J., Grotegerd, Dominik, Gruber, Oliver, Hagenaars, Saskia, Hashimoto, Ryota, Hauser, Tobias U., Heinz, Andreas, Hibar, Derrek P., Hoekstra, Pieter J., Hoogman, Martine, Howells, Fleur M., Hu, Hao, Hulshoff Pol, Hilleke E., Huyser, Chaim, Ittermann, Bernd, Jahanshad, Neda, Jönsson, Erik G., Jurk, Sarah, Kahn, Rene S., Kelly, Sinead, Kraemer, Bernd, Kugel, Harald, Kwon, Jun Soo, Lemaitre, Herve, Lesch, Klaus-Peter, Lochner, Christine, Luciano, Michelle, Marquand, Andre F., Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Martinot, Jean-Luc, Mataix-Cols, David, Mather, Karen, McDonald, Colm, McMahon, Katie L., Medland, Sarah E., Menchón, José M., Morris, Derek W., Mothersill, Omar, Maniega, Susana Munoz, Mwangi, Benson, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswaamy, Janardhanan C., Nees, Frauke, Nordvik, Jan E., Onnink, A. Marten H., Opel, Nils, Ophoff, Roel, Paillère Martinot, Marie-Laure, Papadopoulos Orfanos, Dimitri, Pauli, Paul, Paus, Tomáš, Poustka, Luise, Reddy, Janardhan YC., Renteria, Miguel E., Roiz-Santiáñez, Roberto, Roos, Annerine, Royle, Natalie A., Sachdev, Perminder, Sánchez-Juan, Pascual, Schmaal, Lianne, Schumann, Gunter, Shumskaya, Elena, Smolka, Michael N., Soares, Jair C., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Toro, Roberto, Turner, Jessica A., Tzourio-Mazoyer, Nathalie, Uhlmann, Anne, Hernández, Maria Valdés, van den Heuvel, Odile A., van der Meer, Dennis, van Haren, Neeltje E.M ., Veltman, Dick J., Venkatasubramanian, Ganesan, Vetter, Nora C., Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wang, Zhen, Wardlaw, Joanna, Wen, Wei, Westlye, Lars T., Whelan, Robert, Wittfeld, Katharina, Wolfers, Thomas, Wright, Margaret J., Xu, Jian, Xu, Xiufeng, Yun, Je-Yeon, Zhao, JingJing, Franke, Barbara, Thompson, Paul M., Glahn, David C., Mazoyer, Bernard, Fisher, Simon E., and Francks, Clyde

Published
2016
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32. Probabilistic Inference Strategy in Distributed Intrusion Detection Systems

Author

Ding, Jianguo, Xu, Shihao, Krämer, Bernd, Bai, Yingcai, Chen, Hansheng, Zhang, Jun, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Cao, Jiannong, editor, Yang, Laurence T., editor, Guo, Minyi, editor, and Lau, Francis, editor

Published
2005
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33. Probabilistic Inference for Network Management

Author

Ding, Jianguo, Krämer, Bernd J., Bai, Yingcai, Chen, Hansheng, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Freire, Mário Marques, editor, Chemouil, Prosper, editor, Lorenz, Pascal, editor, and Gravey, Annie, editor

Published
2004
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40. Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years

Author

Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andersson, Micael, Andreasen, Nancy C., Andreassen, Ole A., Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Cervenka, Simon, Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dale, Anders M., Davey, Christopher, de Geus, Eco J. C., de Haan, Lieuwe, de Zubicaray, Greig, I, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Doan, Nhat Trung, Dorum, Erlend S., Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Fuentes-Claramonte, Paola, Glahn, David C., Gotlib, Ian H., Grabe, Hans-Joergen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Gur, Ruben C., Harrison, Ben J., Hartman, Catharine A., Hatton, Sean N., Heinz, Andreas, Heslenfeld, Dirk J., Hibar, Derrek P., Hickie, Ian B., Ho, Beng-Choon, Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kahn, Rene, Kalnin, Andrew, Kanai, Ryota, Klein, Marieke, Klyushnik, Tatyana P., Koenders, Laura, Koops, Sanne, Kraemer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Menchon, Jose M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, de la Foz, Victor Ortiz-Garcia, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sanchez-Juan, Pascual, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Tordesillas-Gutierrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Voelzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Zanetti, Marcus, V, Ziegler, Georg C., Thompson, Paul M., Dima, Danai, Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andersson, Micael, Andreasen, Nancy C., Andreassen, Ole A., Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Cervenka, Simon, Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dale, Anders M., Davey, Christopher, de Geus, Eco J. C., de Haan, Lieuwe, de Zubicaray, Greig, I, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Doan, Nhat Trung, Dorum, Erlend S., Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Fuentes-Claramonte, Paola, Glahn, David C., Gotlib, Ian H., Grabe, Hans-Joergen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Gur, Ruben C., Harrison, Ben J., Hartman, Catharine A., Hatton, Sean N., Heinz, Andreas, Heslenfeld, Dirk J., Hibar, Derrek P., Hickie, Ian B., Ho, Beng-Choon, Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kahn, Rene, Kalnin, Andrew, Kanai, Ryota, Klein, Marieke, Klyushnik, Tatyana P., Koenders, Laura, Koops, Sanne, Kraemer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Menchon, Jose M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, de la Foz, Victor Ortiz-Garcia, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sanchez-Juan, Pascual, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Tordesillas-Gutierrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Voelzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Zanetti, Marcus, V, Ziegler, Georg C., Thompson, Paul M., and Dima, Danai

Abstract

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Published
2022
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