Search

Your search keyword '"Grasby, Katrina"' showing total 14 results
Start Over Author "Grasby, Katrina" Topic genome-wide association study
14 results on '"Grasby, Katrina"'

1. Elucidating the relationship between migraine risk and brain structure using genetic data.

Author

Mitchell BL, Diaz-Torres S, Bivol S, Cuellar-Partida G, Gerring ZF, Martin NG, Medland SE, Grasby KL, Nyholt DR, and Rentería ME

Subjects
Amygdala, Brain diagnostic imaging, Genetic Predisposition to Disease genetics, Hippocampus, Humans, Genome-Wide Association Study methods, Migraine Disorders genetics
Abstract

Migraine is a highly common and debilitating disorder that often affects individuals in their most productive years of life. Previous studies have identified both genetic variants and brain morphometry differences associated with migraine risk. However, the relationship between migraine and brain morphometry has not been examined on a genetic level, and the causal nature of the association between brain structure and migraine risk has not been determined. Using the largest available genome-wide association studies to date, we examined the genome-wide genetic overlap between migraine and intracranial volume, as well as the regional volumes of nine subcortical brain structures. We further focused the identification and biological annotation of genetic overlap between migraine and each brain structure on specific regions of the genome shared between migraine and brain structure. Finally, we examined whether the size of any of the examined brain regions causally increased migraine risk using a Mendelian randomization approach. We observed a significant genome-wide negative genetic correlation between migraine risk and intracranial volume (rG = -0.11, P = 1 × 10-3) but not with any subcortical region. However, we identified jointly associated regional genomic overlap between migraine and every brain structure. Gene enrichment in these shared genomic regions pointed to possible links with neuronal signalling and vascular regulation. Finally, we provide evidence of a possible causal relationship between smaller total brain, hippocampal and ventral diencephalon volume and increased migraine risk, as well as a causal relationship between increased risk of migraine and a larger volume of the amygdala. We leveraged the power of large genome-wide association studies to show evidence of shared genetic pathways that jointly influence migraine risk and several brain structures, suggesting that altered brain morphometry in individuals with high migraine risk may be genetically mediated. Further interrogation of these results showed support for the neurovascular hypothesis of migraine aetiology and shed light on potentially viable therapeutic targets., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2022
Full Text
View/download PDF

2. Genetic variants associated with longitudinal changes in brain structure across the lifespan.

Author

Brouwer RM, Klein M, Grasby KL, Schnack HG, Jahanshad N, Teeuw J, Thomopoulos SI, Sprooten E, Franz CE, Gogtay N, Kremen WS, Panizzon MS, Olde Loohuis LM, Whelan CD, Aghajani M, Alloza C, Alnæs D, Artiges E, Ayesa-Arriola R, Barker GJ, Bastin ME, Blok E, Bøen E, Breukelaar IA, Bright JK, Buimer EEL, Bülow R, Cannon DM, Ciufolini S, Crossley NA, Damatac CG, Dazzan P, de Mol CL, de Zwarte SMC, Desrivières S, Díaz-Caneja CM, Doan NT, Dohm K, Fröhner JH, Goltermann J, Grigis A, Grotegerd D, Han LKM, Harris MA, Hartman CA, Heany SJ, Heindel W, Heslenfeld DJ, Hohmann S, Ittermann B, Jansen PR, Janssen J, Jia T, Jiang J, Jockwitz C, Karali T, Keeser D, Koevoets MGJC, Lenroot RK, Malchow B, Mandl RCW, Medel V, Meinert S, Morgan CA, Mühleisen TW, Nabulsi L, Opel N, de la Foz VO, Overs BJ, Paillère Martinot ML, Redlich R, Marques TR, Repple J, Roberts G, Roshchupkin GV, Setiaman N, Shumskaya E, Stein F, Sudre G, Takahashi S, Thalamuthu A, Tordesillas-Gutiérrez D, van der Lugt A, van Haren NEM, Wardlaw JM, Wen W, Westeneng HJ, Wittfeld K, Zhu AH, Zugman A, Armstrong NJ, Bonfiglio G, Bralten J, Dalvie S, Davies G, Di Forti M, Ding L, Donohoe G, Forstner AJ, Gonzalez-Peñas J, Guimaraes JPOFT, Homuth G, Hottenga JJ, Knol MJ, Kwok JBJ, Le Hellard S, Mather KA, Milaneschi Y, Morris DW, Nöthen MM, Papiol S, Rietschel M, Santoro ML, Steen VM, Stein JL, Streit F, Tankard RM, Teumer A, van 't Ent D, van der Meer D, van Eijk KR, Vassos E, Vázquez-Bourgon J, Witt SH, Adams HHH, Agartz I, Ames D, Amunts K, Andreassen OA, Arango C, Banaschewski T, Baune BT, Belangero SI, Bokde ALW, Boomsma DI, Bressan RA, Brodaty H, Buitelaar JK, Cahn W, Caspers S, Cichon S, Crespo-Facorro B, Cox SR, Dannlowski U, Elvsåshagen T, Espeseth T, Falkai PG, Fisher SE, Flor H, Fullerton JM, Garavan H, Gowland PA, Grabe HJ, Hahn T, Heinz A, Hillegers M, Hoare J, Hoekstra PJ, Ikram MA, Jackowski AP, Jansen A, Jönsson EG, Kahn RS, Kircher T, Korgaonkar MS, Krug A, Lemaitre H, Malt UF, Martinot JL, McDonald C, Mitchell PB, Muetzel RL, Murray RM, Nees F, Nenadić I, Oosterlaan J, Ophoff RA, Pan PM, Penninx BWJH, Poustka L, Sachdev PS, Salum GA, Schofield PR, Schumann G, Shaw P, Sim K, Smolka MN, Stein DJ, Trollor JN, van den Berg LH, Veldink JH, Walter H, Westlye LT, Whelan R, White T, Wright MJ, Medland SE, Franke B, Thompson PM, and Hulshoff Pol HE

Subjects
Aging genetics, Brain, Humans, Magnetic Resonance Imaging, Genome-Wide Association Study, Longevity genetics
Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2022
Full Text
View/download PDF

3. Shared Genetic Etiology between Cortical Brain Morphology and Tobacco, Alcohol, and Cannabis Use.

Author

Rabinowitz JA, Campos AI, Ong JS, García-Marín LM, Alcauter S, Mitchell BL, Grasby KL, Cuéllar-Partida G, Gillespie NA, Huhn AS, Martin NG, Thompson PM, Medland SE, Maher BS, and Rentería ME

Subjects
Adolescent, Brain diagnostic imaging, Humans, Multifactorial Inheritance, Nicotiana genetics, Cannabis, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have identified genetic variants associated with brain morphology and substance use behaviors (SUB). However, the genetic overlap between brain structure and SUB has not been well characterized. We leveraged GWAS summary data of 71 brain imaging measures and alcohol, tobacco, and cannabis use to investigate their genetic overlap using linkage disequilibrium score regression. We used genomic structural equation modeling to model a "common SUB genetic factor" and investigated its genetic overlap with brain structure. Furthermore, we estimated SUB polygenic risk scores (PRS) and examined whether they predicted brain imaging traits using the Adolescent Behavior and Cognitive Development (ABCD) study. We identified 8 significant negative genetic correlations, including between (1) alcoholic drinks per week and average cortical thickness, and (2) intracranial volume with age of smoking initiation. We observed 5 positive genetic correlations, including those between (1) insula surface area and lifetime cannabis use, and (2) the common SUB genetic factor and pericalcarine surface area. SUB PRS were associated with brain structure variation in ABCD. Our findings highlight a shared genetic etiology between cortical brain morphology and SUB and suggest that genetic variants associated with SUB may be causally related to brain structure differences., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2022
Full Text
View/download PDF

4. Ten years of enhancing neuro-imaging genetics through meta-analysis: An overview from the ENIGMA Genetics Working Group.

Author

Medland SE, Grasby KL, Jahanshad N, Painter JN, Colodro-Conde L, Bralten J, Hibar DP, Lind PA, Pizzagalli F, Thomopoulos SI, Stein JL, Franke B, Martin NG, and Thompson PM

Subjects
Humans, Multicenter Studies as Topic, Brain anatomy & histology, Brain diagnostic imaging, Genetics, Genome-Wide Association Study, Mental Disorders diagnostic imaging, Mental Disorders genetics, Mental Disorders pathology, Meta-Analysis as Topic, Nervous System Diseases diagnostic imaging, Nervous System Diseases genetics, Nervous System Diseases pathology, Neuroimaging
Abstract

Here we review the motivation for creating the enhancing neuroimaging genetics through meta-analysis (ENIGMA) Consortium and the genetic analyses undertaken by the consortium so far. We discuss the methodological challenges, findings, and future directions of the genetics working group. A major goal of the working group is tackling the reproducibility crisis affecting "candidate gene" and genome-wide association analyses in neuroimaging. To address this, we developed harmonized analytic methods, and support their use in coordinated analyses across sites worldwide, which also makes it possible to understand heterogeneity in results across sites. These efforts have resulted in the identification of hundreds of common genomic loci robustly associated with brain structure. We have found both pleiotropic and specific genetic effects associated with brain structures, as well as genetic correlations with psychiatric and neurological diseases., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
Full Text
View/download PDF

5. The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area.

Author

Tilot AK, Khramtsova EA, Liang D, Grasby KL, Jahanshad N, Painter J, Colodro-Conde L, Bralten J, Hibar DP, Lind PA, Liu S, Brotman SM, Thompson PM, Medland SE, Macciardi F, Stranger BE, Davis LK, Fisher SE, and Stein JL

Subjects
Genetic Testing methods, Humans, Magnetic Resonance Imaging trends, Multifactorial Inheritance genetics, Organ Size genetics, Quantitative Trait Loci genetics, Biological Evolution, Cerebral Cortex diagnostic imaging, Cerebral Cortex physiology, Genetic Variation genetics, Genome-Wide Association Study methods
Abstract

Structural brain changes along the lineage leading to modern Homo sapiens contributed to our distinctive cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens. We find that alleles with evidence of recent positive polygenic selection over the past 2000-3000 years are associated with increased surface area (SA) of the entire cortex, as well as specific regions, including those involved in spoken language and visual processing. Therefore, polygenic selective pressures impact the structure of specific cortical areas even over relatively recent timescales. Moreover, common sequence variation within human gained enhancers active in the prenatal cortex is associated with postnatal global SA. We show that such variation modulates the function of a regulatory element of the developmentally relevant transcription factor HEY2 in human neural progenitor cells and is associated with structural changes in the inferior frontal cortex. These results indicate that non-coding genomic regions active during prenatal cortical development are involved in the evolution of human brain structure and identify novel regulatory elements and genes impacting modern human brain structure., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Published
2021
Full Text
View/download PDF

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

Author

Hofer E, Roshchupkin GV, Adams HHH, Knol MJ, Lin H, Li S, Zare H, Ahmad S, Armstrong NJ, Satizabal CL, Bernard M, Bis JC, Gillespie NA, Luciano M, Mishra A, Scholz M, Teumer A, Xia R, Jian X, Mosley TH, Saba Y, Pirpamer L, Seiler S, Becker JT, Carmichael O, Rotter JI, Psaty BM, Lopez OL, Amin N, van der Lee SJ, Yang Q, Himali JJ, Maillard P, Beiser AS, DeCarli C, Karama S, Lewis L, Harris M, Bastin ME, Deary IJ, Veronica Witte A, Beyer F, Loeffler M, Mather KA, Schofield PR, Thalamuthu A, Kwok JB, Wright MJ, Ames D, Trollor J, Jiang J, Brodaty H, Wen W, Vernooij MW, Hofman A, Uitterlinden AG, Niessen WJ, Wittfeld K, Bülow R, Völker U, Pausova Z, Bruce Pike G, Maingault S, Crivello F, Tzourio C, Amouyel P, Mazoyer B, Neale MC, Franz CE, Lyons MJ, Panizzon MS, Andreassen OA, Dale AM, Logue M, Grasby KL, Jahanshad N, Painter JN, Colodro-Conde L, Bralten J, Hibar DP, Lind PA, Pizzagalli F, Stein JL, Thompson PM, Medland SE, Sachdev PS, Kremen WS, Wardlaw JM, Villringer A, van Duijn CM, Grabe HJ, Longstreth WT Jr, Fornage M, Paus T, Debette S, Ikram MA, Schmidt H, Schmidt R, and Seshadri S

Subjects
Adult, Aged, Aged, 80 and over, Chromosome Structures, Cognition, Female, Genomics, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Aging genetics, Brain, Genome-Wide Association Study, Mental Disorders genetics, Neurodegenerative Diseases genetics
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.

Published
2020
Full Text
View/download PDF

7. Heritability and GWAS Analyses of Acne in Australian Adolescent Twins.

Author

Mina-Vargas A, Colodro-Conde L, Grasby K, Zhu G, Gordon S, Medland SE, and Martin NG

Subjects
Acne Vulgaris epidemiology, Acne Vulgaris physiopathology, Adolescent, Adult, Australia epidemiology, Child, Diseases in Twins epidemiology, Diseases in Twins physiopathology, Female, Humans, Male, Phenotype, Polymorphism, Single Nucleotide genetics, Registries, Twins, Dizygotic genetics, Twins, Monozygotic genetics, Young Adult, Acne Vulgaris genetics, Diseases in Twins genetics, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

Acne vulgaris is a skin disease with a multifactorial and complex pathology. While several twin studies have estimated that acne has a heritability of up to 80%, the genomic elements responsible for the origin and pathology of acne are still undiscovered. Here we performed a twin-based structural equation model, using available data on acne severity for an Australian sample of 4,491 twins and their siblings aged from 10 to 24. This study extends by a factor of 3 an earlier analysis of the genetic factors of acne. Acne severity was rated by nurses on a 4-point scale (1 = absent to 4 = severe) on up to three body sites (face, back, chest) and on up to three occasions (age 12, 14, and 16). The phenotype that we analyzed was the most severe rating at any site or age. The polychoric correlation for monozygotic twins was higher (r MZ = 0.86, 95% CI [0.81, 0.90]) than for dizygotic twins (r DZ = 0.42, 95% CI [0.35, 0.47]). A model that includes additive genetic effects and unique environmental effects was the most parsimonious model to explain the genetic variance of acne severity, and the estimated heritability was 0.85 (95% CI [0.82, 0.87]). We then conducted a genome-wide analysis including an additional 271 siblings - for a total of 4,762 individuals. A genome-wide association study (GWAS) scan did not detect loci associated with the severity of acne at the threshold of 5E-08 but suggestive association was found for three SNPs: rs10515088 locus 5q13.1 (p = 3.9E-07), rs12738078 locus 1p35.5 (p = 6.7E-07), and rs117943429 locus 18q21.2 (p = 9.1E-07). The 5q13.1 locus is close to PIK3R1, a gene that has a potential regulatory effect on sebocyte differentiation.

Published
2017
Full Text
View/download PDF

8. Genetic association study of childhood aggression across raters, instruments, and age.

Author

Ip, Hill, van der Laan, Camiel, Krapohl, Eva, Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja, St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol, Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke, Adkins, Daniel, Border, Richard, Peterson, Roseann, Prinz, Joseph, Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer, Day, Felix, Hottenga, Jouke-Jan, Allegrini, Andrea, Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José, Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James, Vinkhuyzen, Anna, Shabalin, Andrey, Corley, Robin, Evans, Luke, Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth, Ehli, Erik, Hagenbeek, Fiona, De Zeeuw, Eveline, Van Beijsterveldt, Toos, Larsson, Henrik, Snieder, Harold, Verhulst, Frank, Amin, Najaf, Whipp, Alyce, Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard, Uitterlinden, André, Heath, Andrew, Madden, Pamela, Haavik, Jan, Harris, Jennifer, Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun, Njolstad, Pal, Lu, Qing, Rodriguez, Alina, Henders, Anjali, Mamun, Abdullah, Najman, Jackob, Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara, Silberg, Judy, Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, and Raitakari, Olli

Subjects
Adolescent, Aggression, Child, Child, Preschool, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Infant, Mental Disorders, Retrospective Studies
Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Published
2021

9. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Painter, Jodie N, Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P, Lind, Penelope A, Pizzagalli, Fabrizio, Ching, Christopher RK, McMahon, Mary Agnes B, Shatokhina, Natalia, Zsembik, Leo CP, Thomopoulos, Sophia I, Zhu, Alyssa H, Strike, Lachlan T, Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio AA, Alnæs, Dag, Amlien, Inge K, Andersson, Micael, Ard, Tyler, Armstrong, Nicola J, Ashley-Koch, Allison, Atkins, Joshua R, Bernard, Manon, Brouwer, Rachel M, Buimer, Elizabeth EL, Bülow, Robin, Bürger, Christian, Cannon, Dara M, Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W, Couvy-Duchesne, Baptiste, Dale, Anders M, Dalvie, Shareefa, de Araujo, Tânia K, de Zubicaray, Greig I, de Zwarte, Sonja MC, Braber, Anouk den, 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, Krämer, 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, and Milaneschi, Yuri

Subjects
Biological Sciences, Genetics, Neurosciences, Mental Health, Brain Disorders, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Neurological, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebral Cortex, Cognition, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Organ Size, Parkinson Disease, Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group, General Science & Technology
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

10. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.

Author

Demontis, Ditte, Walters, Raymond K, Martin, Joanna, Mattheisen, Manuel, Als, Thomas D, Agerbo, Esben, Baldursson, Gísli, Belliveau, Rich, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Dumont, Ashley, Eriksson, Nicholas, Gandal, Michael, Goldstein, Jacqueline I, Grasby, Katrina L, Grove, Jakob, Gudmundsson, Olafur O, Hansen, Christine S, Hauberg, Mads Engel, Hollegaard, Mads V, Howrigan, Daniel P, Huang, Hailiang, Maller, Julian B, Martin, Alicia R, Martin, Nicholas G, Moran, Jennifer, Pallesen, Jonatan, Palmer, Duncan S, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Poterba, Timothy, Poulsen, Jesper Buchhave, Ripke, Stephan, Robinson, Elise B, Satterstrom, F Kyle, Stefansson, Hreinn, Stevens, Christine, Turley, Patrick, Walters, G Bragi, Won, Hyejung, Wright, Margaret J, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Andreassen, Ole A, Asherson, Philip, Burton, Christie L, Boomsma, Dorret I, Cormand, Bru, Dalsgaard, Søren, Franke, Barbara, Gelernter, Joel, Geschwind, Daniel, Hakonarson, Hakon, Haavik, Jan, Kranzler, Henry R, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Middeldorp, Christel, Reif, Andreas, Rohde, Luis Augusto, Roussos, Panos, Schachar, Russell, Sklar, Pamela, Sonuga-Barke, Edmund JS, Sullivan, Patrick F, Thapar, Anita, Tung, Joyce Y, Waldman, Irwin D, Medland, Sarah E, Stefansson, Kari, Nordentoft, Merete, Hougaard, David M, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Daly, Mark J, Faraone, Stephen V, Børglum, Anders D, and Neale, Benjamin M

Subjects
ADHD Working Group of the Psychiatric Genomics Consortium, Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Brain, Humans, Genetic Predisposition to Disease, Risk, Cohort Studies, Attention Deficit Disorder with Hyperactivity, Gene Expression Regulation, Polymorphism, Single Nucleotide, Adolescent, Child, Child, Preschool, Female, Male, Genome-Wide Association Study, Genetic Loci, Clinical Research, Mental Health, Human Genome, Pediatric, Prevention, Genetics, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Aetiology, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

Published
2019

11. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Author

Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, and Christiansen, Lene

Subjects
Biological Sciences, Genetics, Brain Disorders, Mental Health, Human Genome, Biotechnology, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Aetiology, Mental health, Neurological, Adolescent, Brain, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intelligence, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

Published
2018

12. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author

Brouwer, Rachel M, Klein, Marieke, Grasby, Katrina L, Schnack, Hugo G, Jahanshad, Neda, Teeuw, Jalmar, Thomopoulos, Sophia I, Sprooten, Emma, Franz, Carol E, Gogtay, Nitin, Kremen, William S, Panizzon, Matthew S, Olde Loohuis, Loes M, Whelan, Christopher D, Aghajani, Moji, Alloza, Clara, Alnæs, Dag, Artiges, Eric, Ayesa-Arriola, Rosa, Barker, Gareth J, Bastin, Mark E, Blok, Elisabet, Bøen, Erlend, Breukelaar, Isabella A, Bright, Joanna K, Buimer, Elizabeth EL, Bülow, Robin, Cannon, Dara M, Ciufolini, Simone, Crossley, Nicolas A, Damatac, Christienne G, Dazzan, Paola, de Mol, Casper L, de Zwarte, Sonja MC, Desrivières, Sylvane, Díaz-Caneja, Covadonga M, Doan, Nhat Trung, Dohm, Katharina, Fröhner, Juliane H, Goltermann, Janik, Grigis, Antoine, Grotegerd, Dominik, Han, Laura KM, Harris, Mathew A, Hartman, Catharina A, Heany, Sarah J, Heindel, Walter, Heslenfeld, Dirk J, Hohmann, Sarah, Ittermann, Bernd, Jansen, Philip R, Janssen, Joost, Jia, Tianye, Jiang, Jiyang, Jockwitz, Christiane, Karali, Temmuz, Keeser, Daniel, Koevoets, Martijn GJC, Lenroot, Rhoshel K, Malchow, Berend, Mandl, René CW, Medel, Vicente, Meinert, Susanne, Morgan, Catherine A, Mühleisen, Thomas W, Nabulsi, Leila, Opel, Nils, de la Foz, Víctor Ortiz-García, Overs, Bronwyn J, Paillère Martinot, Marie-Laure, Redlich, Ronny, Marques, Tiago Reis, Repple, Jonathan, Roberts, Gloria, Roshchupkin, Gennady V, Setiaman, Nikita, Shumskaya, Elena, Stein, Frederike, Sudre, Gustavo, Takahashi, Shun, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, van der Lugt, Aad, van Haren, Neeltje EM, Wardlaw, Joanna M, Wen, Wei, Westeneng, Henk-Jan, Wittfeld, Katharina, Zhu, Alyssa H, Zugman, Andre, Armstrong, Nicola J, Bonfiglio, Gaia, Bralten, Janita, Dalvie, Shareefa, Davies, Gail, Di Forti, Marta, Ding, Linda, Donohoe, Gary, Forstner, Andreas J, and Gonzalez-Peñas, Javier

Subjects
Aging, Neurology & Neurosurgery, Prevention, Longevity, Human Genome, Neurosciences, Brain, Magnetic Resonance Imaging, Brain Disorders, Mental Health, Neurological, Genetics, Humans, Biomedical Imaging, 2.1 Biological and endogenous factors, Psychology, Mental health, Cognitive Sciences, Aetiology, IMAGEN Consortium, Genome-Wide Association Study, Biotechnology
Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Published
2022

13. 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

14. Genetic association study of childhood aggression across raters, instruments, and age

Author

Nicholas G. Martin, S. Alexandra Burt, Louise Arseneault, Fazil Aliev, Luke M. Evans, Hill F. Ip, Beate St Pourcain, Michel G. Nivard, William E. Copeland, Rebecca K. Vinding, Scott Gordon, Koen Bolhuis, Christian J. Hopfer, Gun Peggy Knudsen, Stefan Johansson, Avshalom Caspi, Richard Border, Chandra A. Reynolds, Pål R. Njølstad, Liisa Keltikangas-Järvinen, Dorret I. Boomsma, Klaus Bønnelykke, Teemu Palviainen, Marta Ribasés, Alina Rodriguez, Catharina A. Hartman, Ilkka Seppälä, Christel M. Middeldorp, Rosa Bosch, Jan Haavik, Gail M. Williams, Andrea G. Allegrini, Ruth Ks, John R. B. Perry, Hadi Zafarmand, Chang Jiang, Elizabeth J. Costello, Camiel M. van der Laan, Olli T. Raitakari, Miquel Casas, Isabell Brikell, William G. Iacono, Jaakko Kaprio, John K. Hewitt, Andrew C. Heath, Eero Vuoksimaa, Xiaoran Tong, Gemma Español, Erik A. Ehli, Richie Poulton, Gareth E. Davies, Albertine J. Oldehinkel, Hans Bisgaard, Naomi R. Wray, Ted Reichborn-Kjennerud, Robert Plomin, Michael C. Stallings, Qing Lu, Jackob M. Najman, Daniel E. Adkins, Yi Lu, Harold Snieder, Sally J. Wadsworth, Alexander Neumann, Alexandra Havdahl, Karen Sugden, Kelly L. Klump, Andrew Smolen, Henrik Larsson, Toos C. E. M. van Beijsterveldt, Kenneth Krauter, Tarunveer S. Ahluwalia, Tellervo Korhonen, Andrey A. Shabalin, Joachim Heinrich, Anke R. Hammerschlag, Shelby Marrington, Lærke Sass, Pamela A. F. Madden, Henning Tiemeier, Tanja Vrijkotte, Paul Lichtenstein, Terho Lehtimäki, Ville Karhunen, Cristina Sánchez-Mora, Robin P. Corley, Anna A. E. Vinkhuyzen, Richard J. Rose, Per Magnus, Sabrina Llop, Ilja M. Nolte, S.A. Brown, Christian Hakulinen, Anjali K. Henders, Marie Standl, Silvia Alemany, Gretchen R.B. Saunders, Jouke-Jan Hottenga, Eveline L. de Zeeuw, Meike Bartels, Elisabeth Thiering, José J. Morosoli, Fiona A. Hagenbeek, Laura Pulkki-Råback, Frank C. Verhulst, Martin A. Kennedy, Craig E. Pennell, Eva Krapohl, Kaili Rimfeld, Tetyana Zayats, Lucía Colodro-Conde, Judith B.M. Ensink, André G. Uitterlinden, Natalia Vilor-Tejedor, Felix R. Day, Jennifer R. Harris, George Davey Smith, Qi Chen, Sebastian Lundström, Marjo-Riitta Järvelin, Alyce M. Whipp, Katrina L. Grasby, L. John Horwood, John Pearson, Judy L. Silberg, Paula Rovira, Hermine H. Maes, Carol A. Wang, Roseann E. Peterson, Tamara L. Wall, Andrew J. O. Whitehouse, Maria-Jose Lopez-Espinosa, Najaf Amin, Jess Tyrrell, Danielle M. Dick, Sarah E. Medland, Allison L. Miller, Øyvind Helgeland, Josep Antoni Ramos Quiroga, Joseph M. Boden, Abdullah Mamun, James Scott, María Soler Artigas, Joseph A. Prinz, Lindon J. Eaves, Terrie E. Moffitt, Matt McGue, Jordi Sunyer, Joanna Martin, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Apollo-University Of Cambridge Repository, Ip, Hill F [0000-0003-1991-5019], Sánchez-Mora, Cristina [0000-0003-4211-1107], Nolte, Ilja M [0000-0001-5047-4077], St Pourcain, Beate [0000-0002-4680-3517], Palviainen, Teemu [0000-0002-7847-8384], Colodro-Conde, Lucía [0000-0002-9004-364X], Gordon, Scott [0000-0001-7623-328X], Aliev, Fazil [0000-0001-8357-4699], Karhunen, Ville [0000-0001-6064-1588], Border, Richard [0000-0002-6293-2968], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Day, Felix R [0000-0003-3789-7651], Hottenga, Jouke-Jan [0000-0002-5668-2368], Rimfeld, Kaili [0000-0001-5139-065X], Lu, Yi [0000-0001-9933-3654], Soler Artigas, María [0000-0002-3213-1107], Bosch, Rosa [0000-0002-7596-183X], Ramos Quiroga, Josep Antoni [0000-0003-1622-0350], Neumann, Alexander [0000-0001-6653-3203], Grasby, Katrina [0000-0001-8539-0228], Middeldorp, Christel [0000-0002-6218-0428], Evans, Luke M [0000-0002-7458-1720], Alemany, Silvia [0000-0002-7925-6767], Sass, Lærke [0000-0002-5217-7014], Ruth, Kate [0000-0003-4966-9170], Ehli, Erik A [0000-0002-7865-3015], Hagenbeek, Fiona A [0000-0002-8773-0430], Snieder, Harold [0000-0003-1949-2298], Uitterlinden, André G [0000-0002-7276-3387], Haavik, Jan [0000-0001-7865-2808], Johansson, Stefan [0000-0002-2298-7008], Knudsen, Gun Peggy S [0000-0002-6193-4291], Njolstad, Pal Rasmus [0000-0003-0304-6728], Rodriguez, Alina [0000-0003-1209-8802], Brown, Sandy [0000-0001-8780-0323], Miller, Allison [0000-0003-3816-2251], Keltikangas-Järvinen, Liisa [0000-0002-7977-3852], Havdahl, Alexandra [0000-0002-9268-0423], Perry, John RB [0000-0001-6483-3771], Lehtimäki, Terho [0000-0002-2555-4427], Arseneault, Louise [0000-0002-2938-2191], Boden, Joseph [0000-0003-1502-1608], Pearson, John [0000-0001-5607-4517], Kennedy, Martin [0000-0002-6445-8526], Poulton, Richie [0000-0002-1052-4583], Copeland, William E [0000-0002-1348-7781], Wray, Naomi [0000-0001-7421-3357], Järvelin, Marjo-Riitta [0000-0002-2149-0630], McGue, Matt [0000-0002-5580-1433], Pennell, Craig E [0000-0002-0937-6165], Dick, Danielle M [0000-0002-1636-893X], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Kaprio, Jaakko [0000-0002-3716-2455], Tiemeier, Henning [0000-0002-4395-1397], Davey Smith, George [0000-0002-1407-8314], Oldehinkel, Albertine J [0000-0003-3925-3913], Ribasés, Marta [0000-0003-1039-1116], Lichtenstein, Paul [0000-0003-3037-5287], Plomin, Robert [0000-0002-0756-3629], Bartels, Meike [0000-0002-9667-7555], Nivard, Michel G [0000-0003-2015-1888], Boomsma, Dorret I [0000-0002-7099-7972], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Child and Adolescent Psychiatry / Psychology, Epidemiology, Internal Medicine, Institute for Molecular Medicine Finland, Genetic Epidemiology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Tellervo Korhonen / Principal Investigator, Cognitive and Brain Aging, Faculty Common Matters (Faculty of Medicine), Medicum, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Helsinki Inequality Initiative (INEQ), Faculty Common Matters (Faculty of Education), Psychosocial factors and health, Behavioural Sciences, Department of Public Health, Adult Psychiatry, Epidemiology and Data Science, APH - Aging & Later Life, APH - Methodology, ARD - Amsterdam Reproduction and Development, Graduate School, Child Psychiatry, ACS - Pulmonary hypertension & thrombosis, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Public and occupational health, APH - Health Behaviors & Chronic Diseases, Institut Català de la Salut, [Ip HF] Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. [van der Laan CM] Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Netherlands Institute for the Study of Crime and Law Enforcement, Amsterdam, The Netherlands. [Krapohl EML] Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. [Brikell I] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Sánchez-Mora C, Soler Artigas M, Rovira P, Ribasés M] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Unitat de Genètica Psiquiàtrica, Grup de Recerca en Psiquiatria, Salut Mental i Addicció, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Nolte IM] Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. [Bosch R] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Servei de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Español G] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ramos Quiroga JA, Ribasés M] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Unitat de Genètica Psiquiàtrica, Grup de Recerca en Psiquiatria, Salut Mental i Addicció, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, Amsterdam Reproduction & Development, Perry, John R B [0000-0001-6483-3771], Ip, Hill F. [0000-0003-1991-5019], Nolte, Ilja M. [0000-0001-5047-4077], Ahluwalia, Tarunveer S. [0000-0002-7464-3354], Day, Felix R. [0000-0003-3789-7651], Evans, Luke M. [0000-0002-7458-1720], Ehli, Erik A. [0000-0002-7865-3015], Hagenbeek, Fiona A. [0000-0002-8773-0430], Uitterlinden, André G. [0000-0002-7276-3387], Knudsen, Gun Peggy S. [0000-0002-6193-4291], Perry, John R. B. [0000-0001-6483-3771], Copeland, William E. [0000-0002-1348-7781], Pennell, Craig E. [0000-0002-0937-6165], Dick, Danielle M. [0000-0002-1636-893X], Martin, Nicholas G. [0000-0003-4069-8020], Medland, Sarah E. [0000-0003-1382-380X], Oldehinkel, Albertine J. [0000-0003-3925-3913], Nivard, Michel G. [0000-0003-2015-1888], and Boomsma, Dorret I. [0000-0002-7099-7972]

Subjects
0301 basic medicine, DISORDER, 45/43, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, Child, Psychiatry, 0303 health sciences, trastornos mentales [PSIQUIATRÍA Y PSICOLOGÍA], HERITABILITY, Mental Disorders, Cognition, Genomics, Explained variation, Justice and Strong Institutions, Aggression, Psychiatry and Mental health, Meta-analysis, ADOLESCENCE, Child, Preschool, conducta y mecanismos de la conducta::conducta::síntomas conductuales::agresión [PSIQUIATRÍA Y PSICOLOGÍA], 631/208/212, Female, Biological psychiatry, medicine.symptom, Life Sciences & Biomedicine, Investigative Techniques::Genetic Techniques::Genetic Association Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], BEHAVIOR, RC321-571, Childhood aggression, Clinical psychology, SDG 16 - Peace, Adolescent, Mental Disorders [PSYCHIATRY AND PSYCHOLOGY], Neurosciences. Biological psychiatry. Neuropsychiatry, Single-nucleotide polymorphism, Biology, 3121 Internal medicine, Malalties mentals - Aspectes genètics, Genetic correlation, Article, 1117 Public Health and Health Services, Cellular and Molecular Neuroscience, 03 medical and health sciences, 631/477/2811, SDG 3 - Good Health and Well-being, Human behaviour, medicine, SNP, Humans, GENOME-WIDE ASSOCIATION, Biological Psychiatry, Genetic Association Studies, 030304 developmental biology, Genetic association, Retrospective Studies, técnicas de investigación::técnicas genéticas::estudios de asociación genética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Science & Technology, SDG 16 - Peace, Justice and Strong Institutions, Infant, Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Aggression [PSYCHIATRY AND PSYCHOLOGY], 1103 Clinical Sciences, Agressivitat en els infants, Heritability, 030104 developmental biology, 1701 Psychology, ORIGINS, Research Programm of Donders Centre for Neuroscience, 3111 Biomedicine, TRAJECTORIES, 030217 neurology & neurosurgery, Demography, Genome-Wide Association Study
Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results