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1. Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome

Author

Schnorr, Isabel, Siegl, Anne, Luckhardt, Sonja, Wenz, Söri, Friedrichsen, Hendrik, El Jomaa, Hiba, Steinmann, Annebirth, Kilencz, Tünde, Arteaga-Henríquez, Gara, Ramos-Sayalero, Carolina, Ibanez-Jimenez, Pol, Rosales-Ortiz, Silvia Karina, Bitter, István, Fadeuilhe, Christian, Ferrer, Marc, Lavebratt, Catharina, Réthelyi, János M., Richarte, Vanesa, Rommelse, Nanda, Ramos-Quiroga, Josep Antoni, Arias-Vasquez, Alejandro, Resch, Eduard, Reif, Andreas, Matura, Silke, and Schiweck, Carmen

Published
2024
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2. Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

Author

Duan, Kuaikuai, Chen, Jiayu, Calhoun, Vince D., Jiang, Wenhao, Rootes-Murdy, Kelly, Schoenmacker, Gido, Silva, Rogers F., Franke, Barbara, Buitelaar, Jan K., Hoogman, Martine, Oosterlaan, Jaap, Hoekstra, Pieter J., Heslenfeld, Dirk, Hartman, Catharina A., Sprooten, Emma, Arias-Vasquez, Alejandro, Turner, Jessica A., and Liu, Jingyu

Published
2023
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3. Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes.

Author

Li, Ting, van Rooij, Daan, Roth Mota, Nina, Buitelaar, Jan K, ENIGMA ADHD Working Group, Hoogman, Martine, Arias Vasquez, Alejandro, and Franke, Barbara

Subjects
ENIGMA ADHD Working Group, ADHD, community detection, effect sizes, neuroanatomic heterogeneity, subcortical volume, Brain Disorders, Pediatric, Mental Health, Attention Deficit Disorder (ADD), Clinical Research, Neurosciences, Developmental & Child Psychology, Clinical Sciences, Psychology, Cognitive Sciences
Abstract

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes.MethodsUsing the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks.ResultsExploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men.ConclusionsOur results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

Published
2021

4. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author

Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I, Raygoza Garay, Juan Antonio, Finnicum, Casey T, Liu, Xingrong, Zhernakova, Daria V, Bonder, Marc Jan, Hansen, Tue H, Frost, Fabian, Rühlemann, Malte C, Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A, Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D, Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T, Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I, Burk, Robert D, Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E, van Duijn, Cornelia M, Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A, Ijzerman, Richard G, Jackson, Matthew A, Jaddoe, Vincent WV, Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J, Lieb, Wolfgang, Lusis, Aldons J, Masclee, Ad AM, Moll, Henriette A, Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J, Steves, Claire J, Thorsen, Jonathan, Timpson, Nicholas J, Tito, Raul Y, Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H, Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U, Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy MAE, Arias Vasquez, Alejandro, de Geus, Eco JC, Meyer, Katie A, Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C, Spector, Tim D, Uitterlinden, Andre G, Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M, Franke, Lude, Sanna, Serena, D’Amato, Mauro, and Pedersen, Oluf

Subjects
Microbiology, Biological Sciences, Genetics, Human Genome, Biotechnology, Clinical Research, Digestive Diseases, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Adolescent, Adult, Bifidobacterium, Child, Child, Preschool, Cohort Studies, Female, Gastrointestinal Microbiome, Genetic Variation, Genome-Wide Association Study, Humans, Lactase, Linkage Disequilibrium, Male, Mendelian Randomization Analysis, Metabolism, Quantitative Trait Loci, RNA, Ribosomal, 16S, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P

Published
2021

5. 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

6. Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis.

Author

van Hulzen, Kimm JE, Scholz, Claus J, Franke, Barbara, Ripke, Stephan, Klein, Marieke, McQuillin, Andrew, Sonuga-Barke, Edmund J, PGC ADHD Working Group, Kelsoe, John R, Landén, Mikael, Andreassen, Ole A, PGC Bipolar Disorder Working Group, Lesch, Klaus-Peter, Weber, Heike, Faraone, Stephen V, Arias-Vasquez, Alejandro, and Reif, Andreas

Subjects
PGC ADHD Working Group, PGC Bipolar Disorder Working Group, Humans, Attention Deficit Disorder with Hyperactivity, Bipolar Disorder, Comorbidity, Genome-Wide Association Study, Attention-deficit/hyperactivity disorder, GWAS, bipolar disorder, cross-disorder meta-analysis, genetic correlation, genetic overlap, Human Genome, Pediatric, Genetics, Attention Deficit Hyperactivity Disorder (ADHD), Mental Health, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years old) would be particularly likely to show genetic covariation with ADHD.MethodsGenome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls. We conducted a cross-disorder genome-wide association study meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks.ResultsWe found a significant single nucleotide polymorphism-based genetic correlation between ADHD and BPD in the full and age-restricted samples (rGfull = .64, p = 3.13 × 10-14; rGrestricted = .71, p = 4.09 × 10-16). The meta-analysis between the full BPD sample identified two genome-wide significant (prs7089973 = 2.47 × 10-8; prs11756438 = 4.36 × 10-8) regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the analyses to BPD cases with an early onset yielded one genome-wide significant association (prs58502974 = 2.11 × 10-8) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known expression quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2, and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an allele-specific expressed gene in neuronal tissue.ConclusionsThe single nucleotide polymorphism-based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset.

Published
2017

7. 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

8. ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide

Author

Thompson, Paul M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bearden, Carrie E, Boedhoe, Premika S, Brouwer, Rachel M, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cannon, Dara M, Cohen, Ronald A, Conrod, Patricia J, Dale, Anders M, Deary, Ian J, Dennis, Emily L, de Reus, Marcel A, Desrivieres, Sylvane, Dima, Danai, Donohoe, Gary, Fisher, Simon E, Fouche, Jean-Paul, Francks, Clyde, Frangou, Sophia, Franke, Barbara, Ganjgahi, Habib, Garavan, Hugh, Glahn, David C, Grabe, Hans J, Guadalupe, Tulio, Gutman, Boris A, Hashimoto, Ryota, Hibar, Derrek P, Holland, Dominic, Hoogman, Martine, Pol, Hilleke E Hulshoff, Hosten, Norbert, Jahanshad, Neda, Kelly, Sinead, Kochunov, Peter, Kremen, William S, Lee, Phil H, Mackey, Scott, Martin, Nicholas G, Mazoyer, Bernard, McDonald, Colm, Medland, Sarah E, Morey, Rajendra A, Nichols, Thomas E, Paus, Tomas, Pausova, Zdenka, Schmaal, Lianne, Schumann, Gunter, Shen, Li, Sisodiya, Sanjay M, Smit, Dirk JA, Smoller, Jordan W, Stein, Dan J, Stein, Jason L, Toro, Roberto, Turner, Jessica A, van den Heuvel, Martijn P, van den Heuvel, Odile L, van Erp, Theo GM, van Rooij, Daan, Veltman, Dick J, Walter, Henrik, Wang, Yalin, Wardlaw, Joanna M, Whelan, Christopher D, Wright, Margaret J, Ye, Jieping, and Consortium, for the ENIGMA

Subjects
Biomedical and Clinical Sciences, Health Sciences, Human Genome, Genetics, Neurosciences, Brain Disorders, Mental Illness, Schizophrenia, Mental Health, Biomedical Imaging, 2.1 Biological and endogenous factors, Generic health relevance, Neurological, Good Health and Well Being, Brain Diseases, Genome-Wide Association Study, Humans, Mental Disorders, Multicenter Studies as Topic, ENIGMA Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

Published
2017

9. 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, Neurodegenerative, Human Genome, Brain Disorders, Genetics, Prevention, Aging, Clinical Research, Biotechnology, 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

10. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author

van den Berg, Stéphanie M, de Moor, Marleen HM, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Arias Vasquez, Alejandro, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abdellaoui, Abdel, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Smith, George Davey, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Mbarek, Hamdi, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Nivard, Michel G, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Generation Scotland, Porteous, David, Minelli, Alessandra, and Palmer, Abraham A

Subjects
Biological Psychology, Epidemiology, Health Sciences, Psychology, Human Genome, Genetics, Prevention, 2.1 Biological and endogenous factors, Generic health relevance, Cohort Studies, Extraversion, Psychological, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Personality, Polymorphism, Single Nucleotide, Risk Factors, Generation Scotland, Common genetic variants, Imputation, Phenotype harmonization, Polygenic risk, Zoology, Neurosciences, Genetics & Heredity, Biomedical and clinical sciences, Health sciences
Abstract

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Published
2016

11. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept

Author

Franke, Barbara, Stein, Jason L, Ripke, Stephan, Anttila, Verneri, Hibar, Derrek P, van Hulzen, Kimm JE, Arias-Vasquez, Alejandro, Smoller, Jordan W, Nichols, Thomas E, Neale, Michael C, McIntosh, Andrew M, Lee, Phil, McMahon, Francis J, Meyer-Lindenberg, Andreas, Mattheisen, Manuel, Andreassen, Ole A, Gruber, Oliver, Sachdev, Perminder S, Roiz-Santiañez, Roberto, Saykin, Andrew J, Ehrlich, Stefan, Mather, Karen A, Turner, Jessica A, Schwarz, Emanuel, Thalamuthu, Anbupalam, Yao, Yin, Ho, Yvonne YW, Martin, Nicholas G, Wright, Margaret J, O'Donovan, Michael C, Thompson, Paul M, Neale, Benjamin M, Medland, Sarah E, and Sullivan, Patrick F

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Neurosciences, Schizophrenia, Mental Health, Mental Illness, Brain Disorders, Genetics, 2.1 Biological and endogenous factors, Mental health, Brain, Endophenotypes, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Magnetic Resonance Imaging, Neuroimaging, Organ Size, Polymorphism, Single Nucleotide, Schizophrenia Working Group of the Psychiatric Genomics Consortium, ENIGMA Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

Published
2016

13. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

Author

Genetics of Personality Consortium, de Moor, Marleen HM, van den Berg, Stéphanie M, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Arias Vasquez, Alejandro, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Davey Smith, George, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Porteous, David, Minelli, Alessandra, Palmer, Abraham A, Rujescu, Dan, Ciullo, Marina, and Hayward, Caroline

Subjects
Genetics of Personality Consortium, Humans, Genetic Predisposition to Disease, Cell Adhesion Molecules, Neuronal, Risk Factors, Personality, Anxiety Disorders, Depressive Disorder, Major, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Neuroticism, Adaptor Proteins, Signal Transducing, Cell Adhesion Molecules, Guanylate Kinases, Neuronal, Depressive Disorder, Major, Polymorphism, Single Nucleotide, Adaptor Proteins, Signal Transducing, Other Medical and Health Sciences, Psychology, Cognitive Sciences
Abstract

ImportanceNeuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).ObjectivesTo identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.Design, setting, and participantsGenome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.Main outcomes and measuresNeuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.ResultsA genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12

Published
2015

14. 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

15. The Role of Diet and the Gut Microbiota in Reactive Aggression and Adult ADHD—An Exploratory Analysis.

Author

Jakobi, Babette, Cimetti, Chiara, Mulder, Danique, Vlaming, Priscilla, Franke, Barbara, Hoogman, Martine, and Arias-Vasquez, Alejandro

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition, of-ten persistent into adulthood and accompanied by reactive aggression. Associations of diet and the gut-microbiome with ADHD as well as emotional behaviors suggest potential clinical rele-vance of both. However, studies on diet and the gut-microbiome in human reactive aggression are lacking, and should investigate the interaction between diet and the gut-microbiome leading to behavioral changes to assess their potential clinical relevance. In this study, we investigated the interaction of diet and gut-microbiota with adult ADHD and reactive aggression in 77 adults with ADHD and 76 neurotypical individuals. We studied the relationships of ADHD and reactive ag-gression with dietary patterns, bacterial community and taxonomic differences of 16S-sequenced fecal microbiome samples, and potential mediating effects of bacterial genus abundance on signifi-cant diet-behavior associations. The key findings include: (1) An association of high-energy intake with reactive aggeression scores (pFDR = 4.01 × 10−02); (2) Significant associations of several genera with either reactive aggression or ADHD diagnosis with no overlap; and (3) No significant mediation effects of the selected genera on the association of reactive aggression with the high-energy diet. Our results suggest that diet and the microbiome are linked to reactive aggression and/or ADHD individually, and highlight the need to further study the way diet and the gut-microbiome inter-act. [ABSTRACT FROM AUTHOR]

Published
2024
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20. A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods

Author

Bosch, Annick, Bierens, Margreet, de Wit, Ardine G., Ly, Verena, van der Velde, Jessica, de Boer, Heleen, van Beek, Gerry, Appelman, Danielle, Visser, Sacha, Bos, Lisa, van der Meer, Jolanda, Kamphuis, Niki, Draaisma, Jos M. T., Donders, Rogier, van de Loo-Neus, Gigi H. H., Hoekstra, Pieter J., Bottelier, Marco, Arias-Vasquez, Alejandro, Klip, Helen, Buitelaar, Jan K., van den Berg, Saskia W., and Rommelse, Nanda N.

Published
2020
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22. Serotonin Transporter (SERT) Expression Modulates the Composition of the Western-Diet-Induced Microbiota in Aged Female Mice

Author

Bloemendaal, Mirjam, primary, Veniaminova, Ekaterina, additional, Anthony, Daniel C., additional, Gorlova, Anna, additional, Vlaming, Priscilla, additional, Khairetdinova, Adel, additional, Cespuglio, Raymond, additional, Lesch, Klaus Peter, additional, Arias Vasquez, Alejandro, additional, and Strekalova, Tatyana, additional

Published
2023
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23. Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2

Author

Zazo Seco, Celia, Serrão de Castro, Luciana, van Nierop, Josephine W., Morín, Matías, Jhangiani, Shalini, Verver, Eva J.J., Schraders, Margit, Maiwald, Nadine, Wesdorp, Mieke, Venselaar, Hanka, Spruijt, Liesbeth, Oostrik, Jaap, Schoots, Jeroen, van Reeuwijk, Jeroen, Lelieveld, Stefan H., Huygen, Patrick L.M., Insenser, María, Admiraal, Ronald J.C., Pennings, Ronald J.E., Hoefsloot, Lies H., Arias-Vásquez, Alejandro, de Ligt, Joep, Yntema, Helger G., Jansen, Joop H., Muzny, Donna M., Huls, Gerwin, van Rossum, Michelle M., Lupski, James R., Moreno-Pelayo, Miguel Angel, Kunst, Henricus P.M., and Kremer, Hannie

Published
2015
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25. Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

Author

Bralten, Janita, Greven, Corina U., Franke, Barbara, Mennes, Maarten, Zwiers, Marcel P., Rommelse, Nanda N.J., Hartman, Catharina, van der Meer, Dennis, O'Dwyer, Laurence, Oosterlaan, Jaap, Hoekstra, Pieter J., Heslenfeld, Dirk, Arias-Vasquez, Alejandro, and Buitelaar, Jan K.

Subjects
Attention deficit hyperactivity disorder -- Physiological aspects, Morphometrics (Biology) -- Methods, Health, Psychology and mental health
Abstract

Background: Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. Methods: We performed voxelbased morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Results: Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8-30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Limitations: Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Conclusion: Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research., Introduction Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder characterized by developmentally inappropriate impulsive, hyperactive and/or inattentive symptoms. (1) Previous MRI studies have reported smaller total brain volumes in participants [...]

Published
2016
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26. Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/hyperactivity disorder

Author

Wolfers, Thomas, Onnink, A. Marten H., Zwiers, Marcel P., Arias-Vasquez, Alejandro, Hoogman, Martine, Mostert, Jeanette C., Kan, Cornelis C., Slaats-Willemse, Dorine, Buitelaar, Jan K., and Franke, Barbara

Subjects
Attention-deficit hyperactivity disorder -- Risk factors -- Diagnosis -- Care and treatment -- Research, Health, Psychology and mental health
Abstract

Background: Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. Methods: We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging-derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. Results: We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. Limitations: Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. Conclusion: This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD., Introduction Attention-deficit/hyperactivity disorder (ADHD) is characterized by a pervasive pattern of age-inappropriate inattentive behaviour and/or impulsiveness and hyperactivity. Although ADHD is often viewed as a childhood disorder, it also affects [...]

Published
2015
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28. Association of sweetened carbonated beverage consumption during pregnancy and ADHD symptoms in the offspring:a study from the Norwegian Mother, Father and Child Cohort Study (MoBa)

Author

Kvalvik, Liv Grimstvedt, Klungsøyr, Kari, Igland, Jannicke, Caspersen, Ida Henriette, Brantsæter, Anne Lise, Solberg, Berit Skretting, Hartman, Catharina, Schweren, Lizanne Johanna Stephanie, Larsson, Henrik, Li, Lin, Forthun, Ingeborg, Johansson, Stefan, Arias Vasquez, Alejandro, Haavik, Jan, Kvalvik, Liv Grimstvedt, Klungsøyr, Kari, Igland, Jannicke, Caspersen, Ida Henriette, Brantsæter, Anne Lise, Solberg, Berit Skretting, Hartman, Catharina, Schweren, Lizanne Johanna Stephanie, Larsson, Henrik, Li, Lin, Forthun, Ingeborg, Johansson, Stefan, Arias Vasquez, Alejandro, and Haavik, Jan

Abstract

Purpose: Intrauterine exposures influence offspring health and development. Here we investigated maternal intake of sweetened carbonated beverages (SCB) during pregnancy and its association with ADHD symptoms in the offspring. Methods: This study was based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway. Maternal diet mid-pregnancy was assessed using a food frequency questionnaire (FFQ). All mothers who responded to the FFQ and a questionnaire when their child was 8 years of age were included (n = 39,870). The exposure was defined as maternal intake (daily servings) of SCB, using no daily intake as reference. Outcome was offspring ADHD symptoms, evaluated as a continuous standardized ADHD score and as a binary outcome of six or more ADHD symptoms vs. five symptoms or less. Associations were analysed using log-binomial regression and linear mixed regression models with adjustment for covariates. Results: The adjusted regression coefficients for the standardized ADHD offspring symptom score were 0.31 [95% confidence intervals (0.001, 0.62)] and 0.46 (0.15, 0.77) for maternal daily intake of ≥ 1 glasses of SCB, when the models included adjustments for total energy intake or energy intake from other sources than SCBs and sweet drinks, respectively. The corresponding adjusted relative risks were 1.16 (1.004, 1.34) and 1.21. (1.05, 1.39) for drinking ≥ 1 glasses daily. Conclusion: In a large pregnancy cohort with offspring followed until 8 years of age, we found an association between maternal daily intake of SCB and offspring ADHD symptoms. These results suggest a weak positive relationship between prenatal exposure to SCB and offspring ADHD.

Published
2022

29. Association of sweetened carbonated beverage consumption during pregnancy and ADHD symptoms in the offspring : a study from the Norwegian Mother, Father and Child Cohort Study (MoBa)

Author

Kvalvik, Liv Grimstvedt, Klungsøyr, Kari, Igland, Jannicke, Caspersen, Ida Henriette, Brantsæter, Anne Lise, Solberg, Berit Skretting, Hartman, Catharina, Schweren, Lizanne Johanna Stephanie, Larsson, Henrik, Li, Lin, Forthun, Ingeborg, Johansson, Stefan, Arias Vasquez, Alejandro, Haavik, Jan, Kvalvik, Liv Grimstvedt, Klungsøyr, Kari, Igland, Jannicke, Caspersen, Ida Henriette, Brantsæter, Anne Lise, Solberg, Berit Skretting, Hartman, Catharina, Schweren, Lizanne Johanna Stephanie, Larsson, Henrik, Li, Lin, Forthun, Ingeborg, Johansson, Stefan, Arias Vasquez, Alejandro, and Haavik, Jan

Abstract

PURPOSE: Intrauterine exposures influence offspring health and development. Here we investigated maternal intake of sweetened carbonated beverages (SCB) during pregnancy and its association with ADHD symptoms in the offspring. METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway. Maternal diet mid-pregnancy was assessed using a food frequency questionnaire (FFQ). All mothers who responded to the FFQ and a questionnaire when their child was 8 years of age were included (n = 39,870). The exposure was defined as maternal intake (daily servings) of SCB, using no daily intake as reference. Outcome was offspring ADHD symptoms, evaluated as a continuous standardized ADHD score and as a binary outcome of six or more ADHD symptoms vs. five symptoms or less. Associations were analysed using log-binomial regression and linear mixed regression models with adjustment for covariates. RESULTS: The adjusted regression coefficients for the standardized ADHD offspring symptom score were 0.31 [95% confidence intervals (0.001, 0.62)] and 0.46 (0.15, 0.77) for maternal daily intake of ≥ 1 glasses of SCB, when the models included adjustments for total energy intake or energy intake from other sources than SCBs and sweet drinks, respectively. The corresponding adjusted relative risks were 1.16 (1.004, 1.34) and 1.21. (1.05, 1.39) for drinking ≥ 1 glasses daily. CONCLUSION: In a large pregnancy cohort with offspring followed until 8 years of age, we found an association between maternal daily intake of SCB and offspring ADHD symptoms. These results suggest a weak positive relationship between prenatal exposure to SCB and offspring ADHD., Funding agencies:University of BergenNorwegian Ministry of Health and Care ServicesMinistry of Education and Research

Published
2022
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30. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author

van den Berg, Stéphanie M., de Moor, Marleen H. M., McGue, Matt, Pettersson, Erik, Terracciano, Antonio, Verweij, Karin J. H., Amin, Najaf, Derringer, Jaime, Esko, Tõnu, van Grootheest, Gerard, Hansell, Narelle K., Huffman, Jennifer, Konte, Bettina, Lahti, Jari, Luciano, Michelle, Matteson, Lindsay K., Viktorin, Alexander, Wouda, Jasper, Agrawal, Arpana, Allik, Jüri, Bierut, Laura, Broms, Ulla, Campbell, Harry, Smith, George Davey, Eriksson, Johan G., Ferrucci, Luigi, Franke, Barbera, Fox, Jean-Paul, de Geus, Eco J. C., Giegling, Ina, Gow, Alan J., Grucza, Richard, Hartmann, Annette M., Heath, Andrew C., Heikkilä, Kauko, Iacono, William G., Janzing, Joost, Jokela, Markus, Kiemeney, Lambertus, Lehtimäki, Terho, Madden, Pamela A. F., Magnusson, Patrik K. E., Northstone, Kate, Nutile, Teresa, Ouwens, Klaasjan G., Palotie, Aarno, Pattie, Alison, Pesonen, Anu-Katriina, Polasek, Ozren, Pulkkinen, Lea, Pulkki-Råback, Laura, Raitakari, Olli T., Realo, Anu, Rose, Richard J., Ruggiero, Daniela, Seppälä, Ilkka, Slutske, Wendy S., Smyth, David C., Sorice, Rossella, Starr, John M., Sutin, Angelina R., Tanaka, Toshiko, Verhagen, Josine, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Willemsen, Gonneke, Wright, Margaret J., Zgaga, Lina, Rujescu, Dan, Metspalu, Andres, Wilson, James F., Ciullo, Marina, Hayward, Caroline, Rudan, Igor, Deary, Ian J., Räikkönen, Katri, Arias Vasquez, Alejandro, Costa, Paul T., Keltikangas-Järvinen, Liisa, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Krueger, Robert F., Evans, David M., Kaprio, Jaakko, Pedersen, Nancy L., Martin, Nicholas G., and Boomsma, Dorret I.

Published
2014
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32. Patterns of Gray Matter Abnormalities in Schizophrenia Based on an International Mega-analysis

Author

Gupta, Cota Navin, Calhoun, Vince D., Rachakonda, Srinivas, Chen, Jiayu, Patel, Veena, Liu, Jingyu, Segall, Judith, Franke, Barbara, Zwiers, Marcel P., Arias-Vasquez, Alejandro, Buitelaar, Jan, Fisher, Simon E., Fernandez, Guillen, van Erp, Theo G. M., Potkin, Steven, Ford, Judith, Mathalon, Daniel, McEwen, Sarah, Lee, Hyo Jong, Mueller, Bryon A., Greve, Douglas N., Andreassen, Ole, Agartz, Ingrid, Gollub, Randy L., Sponheim, Scott R., Ehrlich, Stefan, Wang, Lei, Pearlson, Godfrey, Glahn, David C., Sprooten, Emma, Mayer, Andrew R., Stephen, Julia, Jung, Rex E., Canive, Jose, Bustillo, Juan, and Turner, Jessica A.

Published
2015
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35. Correction: Szopinska-Tokov et al. Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms. Microorganisms 2020, 8, 406

Author

Szopinska-Tokov, Joanna, primary, Dam, Sarita, additional, Naaijen, Jilly, additional, Konstanti, Prokopis, additional, Rommelse, Nanda, additional, Belzer, Clara, additional, Buitelaar, Jan, additional, Franke, Barbara, additional, Bloemendaal, Mirjam, additional, Aarts, Esther, additional, and Arias Vasquez, Alejandro, additional

Published
2021
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37. Diet, Physical Activity, and Disinhibition in Middle-Aged and Older Adults : A UK Biobank Study

Author

Schweren, Lizanne J. S., van Rooij, Daan, Shi, Huiqing, Larsson, Henrik, Arias-Vasquez, Alejandro, Li, Lin, Grimstvedt Kvalvik, Liv, Haavik, Jan, Buitelaar, Jan, Hartman, Catharina, Schweren, Lizanne J. S., van Rooij, Daan, Shi, Huiqing, Larsson, Henrik, Arias-Vasquez, Alejandro, Li, Lin, Grimstvedt Kvalvik, Liv, Haavik, Jan, Buitelaar, Jan, and Hartman, Catharina

Abstract

Disinhibition is a prominent feature of multiple psychiatric disorders, and has been associated with poor long-term somatic outcomes. Modifiable lifestyle factors including diet and moderate-to-vigorous physical activity (MVPA) may be associated with disinhibition, but their contributions have not previously been quantified among middle-aged/older adults. Here, among N = 157,354 UK Biobank participants aged 40-69, we extracted a single disinhibition principal component and four dietary components (prudent diet, elimination of wheat/dairy/eggs, meat consumption, full-cream dairy consumption). In addition, latent profile analysis assigned participants to one of five empirical dietary groups: prudent-moderate, unhealthy, restricted, meat-avoiding, low-fat dairy. Disinhibition was regressed on the four dietary components, the dietary grouping variable, and self-reported MVPA. In men and women, disinhibition was negatively associated with prudent diet, and positively associated with wheat/dairy/eggs elimination. In men, disinhibition was also associated with consumption of meat and full-cream dairy products. Comparing groups, disinhibition was lower in the prudent-moderate diet (reference) group compared to all other groups. Absolute βs ranged from 0.02-0.13, indicating very weak effects. Disinhibition was not associated with MVPA. In conclusion, disinhibition is associated with multiple features of diet among middle-aged/older adults. Our findings foster specific hypotheses (e.g., early malnutrition, elevated immune-response) to be tested in alternative study designs.

Published
2021
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38. Diet quality, stress and common mental health problems : A cohort study of 121,008 adults

Author

Schweren, Lizanne J. S., Larsson, Henrik, Vinke, Petra C., Li, Lin, Kvalvik, Liv Grimstvedt, Arias-Vasquez, Alejandro, Haavik, Jan, Hartman, Catharina A., Schweren, Lizanne J. S., Larsson, Henrik, Vinke, Petra C., Li, Lin, Kvalvik, Liv Grimstvedt, Arias-Vasquez, Alejandro, Haavik, Jan, and Hartman, Catharina A.

Abstract

BACKGROUND & AIMS: Overall diet quality may partially mediate the detrimental effects of stress and neuroticism on common mental health problems: stressed and/or neurotic individuals may be more prone to unhealthy dietary habits, which in turn may contribute to depression and anxiety. Lifestyle interventions for depressed, anxious or at-risk individuals hinge on this idea, but evidence to support such pathway is missing. Here, we aim to prospectively evaluate the role of overall diet quality in common pathways to developing depression and anxiety. METHODS: At baseline, N = 121,008 individuals from the general population (age 18-93) completed an extensive food frequency questionnaire, based on which overall diet quality was estimated. Participants also reported on two established risk factors for mental health problems, i.e. past-year stress exposure (long-term difficulties, stressful life-events) and four neuroticism traits (anger-hostility, self-consciousness, impulsivity, vulnerability). Depression and anxiety were assessed at baseline and follow-up (n = 65,342, +3.6 years). Overall diet quality was modeled as a mediator in logistic regression models predicting the development of depression and anxiety from common risk factors. RESULTS: High stress and high neuroticism scores were - albeit weakly - associated with poorer diet quality. Poor diet quality, in turn, did not predict mental health problems. Overall diet quality did not mediate the relationship between stress/neuroticism and common mental health problems: effects of stress, neuroticism and stress-by-neuroticism interactions on mental health problems at follow-up consisted entirely of direct effects (98.6%-100%). CONCLUSIONS: Diet quality plays no mediating role in two established pathways to common mental health problems. As overall diet quality was reduced in stressed and neurotic individuals, these groups may benefit from dietary interventions. However, such interventions are unlikely to prevent th

Published
2021
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39. Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

Author

Li, Ting; https://orcid.org/0000-0002-8408-2482, van Rooij, Daan, Roth Mota, Nina, Buitelaar, Jan K, ENIGMA ADHD Working Group, Hoogman, Martine, Arias Vasquez, Alejandro, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, et al, Brandeis, Daniel, Brem, Silvia; https://orcid.org/0000-0002-8031-1305, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Li, Ting; https://orcid.org/0000-0002-8408-2482, van Rooij, Daan, Roth Mota, Nina, Buitelaar, Jan K, ENIGMA ADHD Working Group, Hoogman, Martine, Arias Vasquez, Alejandro, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, et al, Brandeis, Daniel, Brem, Silvia; https://orcid.org/0000-0002-8031-1305, and Walitza, Susanne; https://orcid.org/0000-0002-8161-8683

Abstract

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes. METHODS Using the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks. RESULTS Exploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men. CONCLUSIONS Our results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

Published
2021

40. Effects of the Mediterranean Diet or Nut Consumption on Gut Microbiota Composition and Fecal Metabolites and their Relationship with Cardiometabolic Risk Factors

Author

Universitat Rovira i Virgili, Galie, Serena; Garcia-Gavilan, Jesus; Camacho-Barcia, Lucia; Atzeni, Alessandro; Muralidharan, Jananee; Papandreou, Christopher; Arcelin, Pierre; Palau-Galindo, Antoni; Garcia, David; Basora, Josep; Arias-Vasquez, Alejandro; Bullo, Monica, Universitat Rovira i Virgili, and Galie, Serena; Garcia-Gavilan, Jesus; Camacho-Barcia, Lucia; Atzeni, Alessandro; Muralidharan, Jananee; Papandreou, Christopher; Arcelin, Pierre; Palau-Galindo, Antoni; Garcia, David; Basora, Josep; Arias-Vasquez, Alejandro; Bullo, Monica

Abstract

Scope To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors. Methods and Results Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g day(-1)). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC-qTOF) platforms in a targeted metabolomics approach. Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA-IR, while positively and negatively with changes in cholate and cadaverine, respectively. Conclusions Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.

Published
2021

41. A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population

Author

Fan Liu, Arias-Vasquez, Alejandro, Sleegers, Kristel, Aulchenko, Yurii S., Kayser, Manfred, Sanchez-Juan, Pascual, Bing-Jian Feng, Bertoli-Avella, Aida M., Van Swieten, Johnc, Axenovich, Tatiana I., Heutink, Peter, Van Broeckhoven, Christine, Oostra, Ben A., and Van Duijn, Cornelia M.

Subjects
Alzheimer's disease -- Genetic aspects, Alzheimer's disease -- Research, Dutch -- Genetic aspects, Dutch -- Research, Genetic research, Biological sciences
Abstract

A genomewide screen of the families with late-onset Alzheimer's disease (AD) is a genetically isolated community from the southwestern area of The Netherlands is presented. This genomewide screen has displayed significant linkage to chromosome 3q23 markers and the analysis has confirmed linkage to chromosome 11q25.

Published
2007

44. Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms

Author

Szopinska-Tokov, Joanna, primary, Dam, Sarita, additional, Naaijen, Jilly, additional, Konstanti, Prokopis, additional, Rommelse, Nanda, additional, Belzer, Clara, additional, Buitelaar, Jan, additional, Franke, Barbara, additional, Bloemendaal, Mirjam, additional, Aarts, Esther, additional, and Arias Vasquez, Alejandro, additional

Published
2020
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45. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Author

Hofer, Edith, Roshchupkin, Gennady V, Bernard, Manon, Grasby, Katrina L, Jahanshad, Neda, Painter, Jodie N, Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P, Lind, Penelope A, Pizzagalli, Fabrizio, Ching, Christopher R K, McMahon, Mary Agnes B, Bis, Joshua C, Shatokhina, Natalia, Zsembik, Leo C P, Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A A, Alnæs, Dag, Amlien, Inge K, Andersson, Micael, Ard, Tyler, Armstrong, Nicola J, Gillespie, Nathan A, Ashley-Koch, Allison, Brouwer, Rachel M, Buimer, Elizabeth E L, Bülow, Robin, Bürger, Christian, Cannon, Dara M, Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W, Luciano, Michelle, Couvy-Duchesne, Baptiste, Dale, Anders M, Dalvie, Shareefa, de Araujo, Tânia K, de Zubicaray, Greig I, de Zwarte, Sonja M C, den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Mishra, Aniket, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O, Foley, Sonya F, Ford, Judith M, Fukunaga, Masaki, Garrett, Melanie E, Ge, Tian, Giddaluru, Sudheer, Scholz, Markus, Goldman, Aaron L, Groenewold, Nynke A, Grotegerd, Dominik, Gurholt, Tiril P, Gutman, Boris A, Hansell, Narelle K, Harris, Mathew A, Harrison, Marc B, Haswell, Courtney C, Hauser, Michael, Teumer, Alexander, Herms, Stefan, Heslenfeld, Dirk J, Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Xia, Rui, Jansen, Iris E, Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Jian, Xueqiu, Knapp, Michael, Knodt, Annchen R, Krämer, Bernd, Lam, Max, Lancaster, Thomas M, Lee, Phil H, Lett, Tristram A, Lewis, Lindsay B, Lopes-Cendes, Iscia, Mosley, Thomas H, Macciardi, Fabio, Marquand, Andre F, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Adams, Hieab H H, Saba, Yasaman, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Pitcher, Toni L, Pütz, Benno, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Redlich, Ronny, Pirpamer, Lukas, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Seiler, Stephan, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Becker, James T, Strike, Lachlan T, Tansey, Katherine E, Thalamuthu, Anbupalam, Thomopoulos, Sophia I, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, Carmichael, Owen, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Rotter, Jerome I, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Yasuda, Clarissa L, Psaty, Bruce M, Zaremba, Dario, Zhang, Zuo, Zhu, Alyssa H, Zwiers, Marcel P, Artiges, Eric, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Lopez, Oscar L, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Amin, Najaf, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, van der Lee, Sven J, Jang, MiHyun, Jansen, Andreas, Kolskår, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Knol, Maria J, Yang, Qiong, Matthews, Sarah, Son, Jaqueline Mayoral Van, McEwen, Sarah C, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Himali, Jayandra J, Opel, Nils, Martinot, Marie -Laure Paillère, Pike, G Bruce, Preda, Adrian, Quinlan, Erin B, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Torres, Fábio R, Veltman, Dick J, Maillard, Pauline, Voyvodic, James T, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Alvim, Marina K M, Ames, David, Anderson, Tim J, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Beiser, Alexa S, Baune, Bernhard T, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Calhoun, Vince, DeCarli, Charles, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E, Flor, Herta, Forstner, Andreas J, Francks, Clyde, Lewis, Lindsay, Franke, Barbara, Glahn, David C, Gollub, Randy L, Grabe, Hans J, Gruber, Oliver, Håberg, Asta K, Hariri, Ahmad R, Hartman, Catharina A, Hashimoto, Ryota, Heinz, Andreas, Harris, Mat, Hillegers, Manon H J, Hoekstra, Pieter J, Holmes, Avram J, Hong, L Elliot, Hopkins, William D, Hulshoff Pol, Hilleke E, Jernigan, Terry L, Jönsson, Erik G, Kahn, René S, Kennedy, Martin A, Kircher, Tilo T J, Kochunov, Peter, Kwok, John B J, Hellard, Stephanie Le, Martin, Nicholas G, Martinot, Jean -Luc, McDonald, Colm, McMahon, Katie L, Meyer-Lindenberg, Andreas, Morey, Rajendra A, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A, Paus, Tomáš, Pausova, Zdenka, Penninx, Brenda W J H, Polderman, Tinca J C, Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L, Lin, Honghuang, Veronica Witte, A., Rowland, Laura M, Sachdev, Perminder S, Sämann, Philipp G, Schumann, Gunter, Sim, Kang, Sisodiya, Sanjay M, Smoller, Jordan W, Sommer, Iris E, Pourcain, Beate St, Stein, Dan J, Beyer, Frauke, Toga, Arthur W, Trollor, Julian N, Van der Wee, Nic J A, van 't Ent, Dennis, Völzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R, Wright, Margaret J, Zhou, Juan, Loeffler, Markus, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, Kwok, John B, Trollor, Julian, Li, Shuo, Jiang, Jiyang, Vernooij, Meike W, Hofman, Albert, Uitterlinden, André G, Niessen, Wiro J, Völker, Uwe, Zare, Habil, Bruce Pike, G., Maingault, Sophie, Crivello, Fabrice, Tzourio, Christophe, Amouyel, Philippe, Mazoyer, Bernard, Neale, Michael C, Franz, Carol E, Lyons, Michael J, Ahmad, Shahzad, Panizzon, Matthew S, Logue, Mark, consortium, ENIGMA, Kremen, William S, Villringer, Arno, Satizabal, Claudia L, van Duijn, Cornelia M, Grabe, Hans, Longstreth, William T, Fornage, Myriam, Paus, Tomas, Debette, Stephanie, Ikram, M Arfan, Schmidt, Helena, Schmidt, Reinhold, Seshadri, Sudha, University of Graz, Medical University Graz, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), School of Public Health [Boston], University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), The University of Texas at San Antonio (UTSA), Murdoch University, The Hospital for sick children [Toronto] (SickKids), University of Washington [Seattle], Virginia Commonwealth University (VCU), QIMR Berghofer Medical Research Institute, University of Edinburgh, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Leipzig [Leipzig], Universität Greifswald - University of Greifswald, University of Mississippi Medical Center (UMMC), University of California [Davis] (UC Davis), University of California, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Pennington Biomedical Research Center, Louisiana State University (LSU), Los Angeles Biomedical Research Institute (LA BioMed), McGill University = Université McGill [Montréal, Canada], Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft, University of New South Wales [Sydney] (UNSW), Neuroscience Research Australia (NeuRA), The University of Sydney, University of Queensland [Brisbane], The Royal Melbourne Hospital, University of Melbourne, Harvard T.H. Chan School of Public Health, Delft University of Technology (TU Delft), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Toronto, University of Calgary, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of California [San Diego] (UC San Diego), University of Oslo (UiO), Oslo University Hospital [Oslo], VA Boston Healthcare System, University of Southern California (USC), Radboud University Medical Center [Nijmegen], Radboud university [Nijmegen], Janssen Research & Development, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Prince of Wales Hospital, University Hospital Leipzig, University of Oxford [Oxford], Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], Epidemiology, Medical Informatics, Radiology & Nuclear Medicine, Neurology, Complex Trait Genetics, Biological Psychology, Cognitive Psychology, IBBA, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Clinical Neuropsychology, Clinical Developmental Psychology, Amsterdam Neuroscience - Complex Trait Genetics, Movement Disorder (MD), Clinical Cognitive Neuropsychiatry Research Program (CCNP), General Paediatrics, ARD - Amsterdam Reproduction and Development, Karl-Franzens-Universität Graz, Universität Leipzig, University of California (UC), Radboud University [Nijmegen], University of Oxford, Psychiatry, Anatomy and neurosciences, Pediatric surgery, Human genetics, APH - Digital Health, and Karl-Franzens-Universität [Graz, Autriche]

Subjects
0301 basic medicine, Male, Genetics of the nervous system, Aging, General Physics and Astronomy, Genome-wide association study, Disease, VARIANTS, genetics [Mental Disorders], Genome-wide association studies, 0302 clinical medicine, Cognition, PARKINSONS-DISEASE, SCHIZOPHRENIA, 80 and over, 2.1 Biological and endogenous factors, Aetiology, lcsh:Science, Aged, 80 and over, education.field_of_study, Multidisciplinary, ENIGMA consortium, Mental Disorders, Brain, Neurodegenerative Diseases, Genomics, Single Nucleotide, Middle Aged, Biobank, ALZHEIMERS-DISEASE, Phenotype, VINTAGE, Neurology, Chromosome Structures, Schizophrenia, genetics [Aging], Neurological, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, ddc:500, Biotechnology, Adult, Science, geentics of the nervous system, 1.1 Normal biological development and functioning, Population, SURFACE-AREA, ORGANIZATION, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Underpinning research, THICKNESS, medicine, Genetics, Humans, Polymorphism, education, HEALTHY, METAANALYSIS, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Genetic heterogeneity, neurology, Human Genome, Neurosciences, General Chemistry, Heritability, medicine.disease, Brain Disorders, INDIVIDUALS, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Evolutionary biology, genetics [Neurodegenerative Diseases], VOLUME, genome-wide association studies, lcsh:Q, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging., Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Published
2020
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46. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L, Mazoyer, Bernard, Mosley, Thomas H, Roshchupkin, Gennady V, Satizabal, Claudia L, Schmidt, Reinhold, Seshadri, Sudha, Bernard, Manon, Yang, Qiong, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, Consortium, EPIGEN, Consortium, IMAGEN, Consortium, SYS, Initiative, Parkinson’s Progression Markers, Alvim, Marina K M, Ames, David, Anderson, Tim J, Brouwer, Rachel M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Baune, Bernhard T, Beckham, Jean C, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buimer, Elizabeth E L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Cairns, Murray J, Calhoun, Vince, Carr, Vaughan J, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Bülow, Robin, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Bürger, 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Tremont, Geoffrey, Bartzokis, George, Groenewold, Nynke A, Hsiung, Ging-Yuek Robin, Malferrari, Giulia, Chiang, Gloria, Pearlson, Godfrey D, Liang, Grace, Jicha, Greg, Sorensen, Greg, Todd, Gretchen, Jimenez, Gustavo, Grotegerd, Dominik, Zare, Habil, Grabe, Hans Jörgen, Vanderswag, Helen, Schmidt, Helena, Venkov, Heli, Lemaitre, Hervé, Gurholt, Tiril P, Grossman, Hillel, Shill, Holly, Soares, Holly, Lin, Honghuang, Capote, Horacio, Bergman, Howard, Chertkow, Howard, Feldman, Howard, Fillit, Howard, Rosen, Howard J, Gutman, Boris A, Koleva, Hristina, Fernandez, Hubert, Garavan, Hugh, Shim, Hyungsub, Grachev, Igor D, Richard, Irene, Filippi, Irina, Rachinsky, Irina, Wurster, Isabel, Lind, Penelope A, Hansell, Narelle K, Mintzer, Jacobo, Ziolkowski, Jaimie, Brewer, James, Lah, James J, Leverenz, James, Becker, James T, Tetrud, James, Singleton-Garvin, Jamika, Egebjerg, Jan, Cellar, Janet S, Harris, Mathew A, Pentilla, Jani, Brosch, Jared R, Tinklenberg, Jared, Karlawish, Jason H, Meyer, Javier Villanueva, Himali, Jayandra J, Poline, Jean-Baptiste, Gunter, Jeff, Kaye, Jeffrey A, Harrison, Marc B, Dalley, Jeffrey, Burns, Jeffrey M, Petrella, Jeffrey R, Mule, Jennifer, Salazar, Jennifer, Rotter, Jerome I, Yesavage, Jerome, Cedarbaum, Jesse, Jiang, Jiyang, Haswell, Courtney C, Allard, Joanne, Lord, Joanne L, Hetelle, Joel, Kwok, John B, Brockington, John, Morris, John C, Hsiao, John, Morris, John, Olichney, John, Trojanowki, John Q, Hauser, Michael, Rogers, John, Seibyl, John, Yankey, Jon, Dubow, Jordan S, Jankovic, Joseph, Quinn, Joseph, Kass, Joseph S, Taylor, Joy L, Heidebrink, Judith L, Herms, Stefan, Trollor, Julian, Fröhner, Juliane, Anderson, Karen, Blank, Karen, Crawford, Karen, Smith, Karen Ekstam, Bell, Karen L, Williams, Karen, Kieburtz, Karl, Heslenfeld, Dirk J, Gauss, Katharina, Gloer, Katherine, Johnson, Kathleen, Tingus, Kathleen, DeMarco, Kathryn, Sink, Kaycee M, Hawkins, Keith A, Johnson, Keith A, Kantarci, Kejal, Ho, New Fei, Faber, Kelley, Harless, Kelly, Makino, Kelly M, Marek, Kenneth, Spicer, Kenneth, Shianna, Kevin, Chen, Kewei, Nam, Ki Won, Martin, Kim, Poki-Walker, Kim, Hoehn, David, Seppi, Klaus, Johnson, Kris, Fargher, Kristin, Lipowski, Kristine, Espay, Kristy, Womack, Kyle, Chahine, Lama, Flashman, Laura A, Daedelow, Laura, Hoffmann, Per, Leary, Laura, Beckett, Laurel, Honig, Lawrence S, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Apostolova, Liana, Teodoro, Liberty, Rees, Linda, Pizzagalli, Fabrizio, Holleran, Laurena, Lewis, Lindsay, Hergesheimer, Lindsey, Silbert, Lisa C, Ravdin, Lisa, Taylor-Reinwald, Lisa, Uribe, Liz, Schneider, Lon S, Daiello, Lori A, Richer, Louis, Poustka, Luise, Hoogman, Martine, Pirpamer, Lukas, Mesulam, M Marcel, Ismail, M Saleem, Ranola, Madelaine, Korecka, Magdalena, Raichle, Marc, Seltzer, Marc, van der Brug, Marcel, Hottenga, Jouke-Jan, Mesulam, Marek-Marsel, Carrillo, Maria, Carroll, Maria, Knol, Maria J, Kataki, Maria, Greig-Custo, Maria T, Paillere, Marie-Laure, Albert, Marilyn, Love, 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Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020
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47. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucia, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R. K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C. P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A. A., Alnaes, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E. L., Bulow, Robin, Burger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tania K., de Zubicaray, Greig I., de Zwarte, Sonja M. C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Kramer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C. V., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Loohuis, Loes M. Olde, Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Putz, Benno, Quide, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Celine S., Repple, Jonathan, Richard, Genevieve, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sonderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutierrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M. J., van Eijk, Liza, van Erp, Theo G. M., van Haren, Neeltje E. M., van Rooij, Daan, van Tol, Marie-Jose, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Hausler, Alexander N., Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jr., Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskar, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, Van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Noethen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie-Laure Paillere, Pike, G. Bruce, Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fabio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H. H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Ikram, M. Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Mazoyer, Bernard, Mosley, Thomas H., Roshchupkin, Gennady V., Satizabal, Claudia L., Schmidt, Reinhold, Seshadri, Sudha, Yang, Qiong, Alvim, Marina K. M., Ames, David, Anderson, Tim J., Andreassen, Ole A., Arias-Vasquez, Alejandro, Bastin, Mark E., Baune, Bernhard T., Beckham, Jean C., Blangero, John, Boomsma, Dorret I., Brodaty, Henry, Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bustillo, Juan R., Cahn, Wiepke, Cairns, Murray J., Calhoun, Vince, Carr, Vaughan J., Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L., Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dannlowski, Udo, de Geus, Eco J. C., Deary, Ian J., Delanty, Norman, Depondt, Chantal, Desrivieres, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernandez, Guillen, Fisher, Simon E., Flor, Herta, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Glahn, David C., Gollub, Randy L., Grabe, Hans J., Gruber, Oliver, Haberg, Asta K., Hariri, Ahmad R., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A., Hillegers, Manon H. J., Hoekstra, Pieter J., Holmes, Avram J., Hong, L. Elliot, Hopkins, William D., Pol, Hilleke E. Hulshoff, Jernigan, Terry L., Jonsson, Erik G., Kahn, Rene S., Kennedy, Martin A., Kircher, Tilo T. J., Kochunov, Peter, Kwok, John B. J., Le Hellard, Stephanie, Loughland, Carmel M., Martin, Nicholas G., Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L., Meyer-Lindenberg, Andreas, Michie, Patricia T., Morey, Rajendra A., Mowry, Bryan, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A., Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Polderman, Tinca J. C., Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L., Rowland, Laura M., Sachdev, Perminder S., Samann, Philipp G., Schall, Ulrich, Schumann, Gunter, Scott, Rodney J., Sim, Kang, Sisodiya, Sanjay M., Smoller, Jordan W., Sommer, Iris E., St Pourcain, Beate, Stein, Dan J., Toga, Arthur W., Trollor, Julian N., Van der Wee, Nic J. A., van't Ent, Dennis, Volzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R., Wright, Margaret J., Zhou, Juan, Stein, Jason L., Thompson, Paul M., Medland, Sarah E., Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucia, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R. K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C. P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A. A., Alnaes, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E. L., Bulow, Robin, Burger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tania K., de Zubicaray, Greig I., de Zwarte, Sonja M. C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Kramer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C. V., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Loohuis, Loes M. Olde, Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Putz, Benno, Quide, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Celine S., Repple, Jonathan, Richard, Genevieve, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sonderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutierrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M. J., van Eijk, Liza, van Erp, Theo G. M., van Haren, Neeltje E. M., van Rooij, Daan, van Tol, Marie-Jose, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Hausler, Alexander N., Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jr., Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskar, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, Van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Noethen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie-Laure Paillere, Pike, G. Bruce, Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fabio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H. H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Ikram, M. Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Mazoyer, Bernard, Mosley, Thomas H., Roshchupkin, Gennady V., Satizabal, Claudia L., Schmidt, Reinhold, Seshadri, Sudha, Yang, Qiong, Alvim, Marina K. M., Ames, David, Anderson, Tim J., Andreassen, Ole A., Arias-Vasquez, Alejandro, Bastin, Mark E., Baune, Bernhard T., Beckham, Jean C., Blangero, John, Boomsma, Dorret I., Brodaty, Henry, Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bustillo, Juan R., Cahn, Wiepke, Cairns, Murray J., Calhoun, Vince, Carr, Vaughan J., Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L., Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dannlowski, Udo, de Geus, Eco J. C., Deary, Ian J., Delanty, Norman, Depondt, Chantal, Desrivieres, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernandez, Guillen, Fisher, Simon E., Flor, Herta, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Glahn, David C., Gollub, Randy L., Grabe, Hans J., Gruber, Oliver, Haberg, Asta K., Hariri, Ahmad R., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A., Hillegers, Manon H. J., Hoekstra, Pieter J., Holmes, Avram J., Hong, L. Elliot, Hopkins, William D., Pol, Hilleke E. Hulshoff, Jernigan, Terry L., Jonsson, Erik G., Kahn, Rene S., Kennedy, Martin A., Kircher, Tilo T. J., Kochunov, Peter, Kwok, John B. J., Le Hellard, Stephanie, Loughland, Carmel M., Martin, Nicholas G., Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L., Meyer-Lindenberg, Andreas, Michie, Patricia T., Morey, Rajendra A., Mowry, Bryan, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A., Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Polderman, Tinca J. C., Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L., Rowland, Laura M., Sachdev, Perminder S., Samann, Philipp G., Schall, Ulrich, Schumann, Gunter, Scott, Rodney J., Sim, Kang, Sisodiya, Sanjay M., Smoller, Jordan W., Sommer, Iris E., St Pourcain, Beate, Stein, Dan J., Toga, Arthur W., Trollor, Julian N., Van der Wee, Nic J. A., van't Ent, Dennis, Volzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R., Wright, Margaret J., Zhou, Juan, Stein, Jason L., Thompson, Paul M., and Medland, Sarah E.

Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020
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48. Attention-deficit/hyperactivity disorder symptoms and dietary habits in adulthood : A large population-based twin study in Sweden

Author

Li, Lin, Taylor, Mark J., Balter, Katarina, Kuja-Halkola, Ralf, Chen, Qi, Hegvik, Tor-Arne, Tate, Ashley E., Chang, Zheng, Arias-Vasquez, Alejandro, Hartman, Catharina A., Larsson, Henrik, Li, Lin, Taylor, Mark J., Balter, Katarina, Kuja-Halkola, Ralf, Chen, Qi, Hegvik, Tor-Arne, Tate, Ashley E., Chang, Zheng, Arias-Vasquez, Alejandro, Hartman, Catharina A., and Larsson, Henrik

Abstract

Associations between adult attention-deficit/hyperactivity disorder (ADHD) symptoms and dietary habits have not been well established and the underlying mechanisms remain unclear. We explored these associations using a Swedish population-based twin study with 17,999 individuals aged 20-47 years. We estimated correlations between inattention and hyperactivity/impulsivity with dietary habits and fitted twin models to determine the genetic and environmental contributions. Dietary habits were defined as (a) consumption of food groups, (b) consumption of food items rich in particular macronutrients, and (c) healthy and unhealthy dietary patterns. At the phenotypic level, inattention was positively correlated with seafood, high-fat, high-sugar, high-protein food consumptions, and unhealthy dietary pattern, with correlation coefficients ranging from 0.03 (95%CI: 0.01, 0.05) to 0.13 (95% CI: 0.11, 0.15). Inattention was negatively correlated with fruits, vegetables consumptions and healthy dietary pattern, with correlation coefficients ranging from -0.06 (95%CI: -0.08, -0.04) to -0.07 (95%CI: -0.09, -0.05). Hyperactivity/impulsivity and dietary habits showed similar but weaker patterns compared to inattention. All associations remained stable across age, sex and socioeconomic status. Nonshared environmental effects contributed substantially to the correlations of inattention (56-60%) and hyperactivity/impulsivity (63-80%) with dietary habits. The highest and lowest genetic correlations were between inattention and high-sugar food (r(A)= .16, 95% CI: 0.07, 0.25), and between hyperactivity/impulsivity and unhealthy dietary pattern (r(A)= .05, 95% CI: -0.05, 0.14), respectively. We found phenotypic and etiological overlap between ADHD and dietary habits, although these associations were weak. Our findings contribute to a better understanding of common etiological pathways between ADHD symptoms and various dietary habits.

Published
2020
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49. A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods

Author

HEE Team 1, JC onderzoeksprogramma Methodologie, Circulatory Health, Bosch, Annick, Bierens, Margreet, de Wit, Ardine G, Ly, Verena, van der Velde, Jessica, de Boer, Heleen, van Beek, Gerry, Appelman, Danielle, Visser, Sacha, Bos, Lisa, van der Meer, Jolanda, Kamphuis, Niki, Draaisma, Jos M T, Donders, Rogier, van de Loo-Neus, Gigi H H, Hoekstra, Pieter J, Bottelier, Marco, Arias-Vasquez, Alejandro, Klip, Helen, Buitelaar, Jan K, van den Berg, Saskia W, Rommelse, Nanda N, HEE Team 1, JC onderzoeksprogramma Methodologie, Circulatory Health, Bosch, Annick, Bierens, Margreet, de Wit, Ardine G, Ly, Verena, van der Velde, Jessica, de Boer, Heleen, van Beek, Gerry, Appelman, Danielle, Visser, Sacha, Bos, Lisa, van der Meer, Jolanda, Kamphuis, Niki, Draaisma, Jos M T, Donders, Rogier, van de Loo-Neus, Gigi H H, Hoekstra, Pieter J, Bottelier, Marco, Arias-Vasquez, Alejandro, Klip, Helen, Buitelaar, Jan K, van den Berg, Saskia W, and Rommelse, Nanda N

Published
2020

50. Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis

Author

van Hulzen, Kimm J E, Scholz, Claus J, Franke, Barbara, Ripke, Stephan, Klein, Marieke, McQuillin, Andrew, Sonuga-Barke, Edmund J S, PGC ADHD Working Group, Kelsoe, John R, Landén, Mikael, Andreassen, Ole A, et al, Walitza, Susanne, Steinhausen, Hans-Christoph, PGC Bipolar Disorder Working Group, Lesch, Klaus-Peter, Weber, Heike, Faraone, Stephen V, Arias-Vasquez, Alejandro, Reif, Andreas, University of Zurich, and Arias-Vasquez, Alejandro

Subjects
610 Medicine & health, 10058 Department of Child and Adolescent Psychiatry, 2803 Biological Psychiatry
Published
2017

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