473 results on '"Anney, Richard"'
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2. Common risk alleles for schizophrenia within the major histocompatibility complex predict white matter microstructure
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Caseras, Xavier, Simmonds, Emily, Pardiñas, Antonio F., Anney, Richard, Legge, Sophie E., Walters, James T. R., Harrison, Neil A., O’Donovan, Michael C., and Escott-Price, Valentina
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- 2024
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3. Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
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Caseras, Xavier, Legge, Sophie E., Bracher-Smith, Matthew, Anney, Richard, Owen, Michael J., Escott-Price, Valentina, and Kirov, George
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- 2023
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4. Characterising depression trajectories in young people at high familial risk of depression
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Weavers, Bryony, Riglin, Lucy, Martin, Joanna, Anney, Richard, Collishaw, Stephan, Heron, Jon, Thapar, Ajay, Thapar, Anita, and Rice, Frances
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- 2023
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5. A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants
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Chawner, Samuel JRA, Doherty, Joanne L, Anney, Richard JL, Antshel, Kevin M, Bearden, Carrie E, Bernier, Raphael, Chung, Wendy K, Clements, Caitlin C, Curran, Sarah R, Cuturilo, Goran, Fiksinski, Ania M, Gallagher, Louise, Goin-Kochel, Robin P, Gur, Raquel E, Hanson, Ellen, Jacquemont, Sebastien, Kates, Wendy R, Kushan, Leila, Maillard, Anne M, McDonald-McGinn, Donna M, Mihaljevic, Marina, Miller, Judith S, Moss, Hayley, Pejovic-Milovancevic, Milica, Schultz, Robert T, Green-Snyder, LeeAnne, Vorstman, Jacob A, Wenger, Tara L, Hall, Jeremy, Owen, Michael J, and van den Bree, Marianne BM
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Clinical Research ,Genetics ,Prevention ,Human Genome ,Intellectual and Developmental Disabilities (IDD) ,Behavioral and Social Science ,Autism ,Pediatric ,Brain Disorders ,Mental Health ,Genetic Testing ,Aetiology ,2.1 Biological and endogenous factors ,Autistic Disorder ,Child ,DNA Copy Number Variations ,Gene Deletion ,Genetic Association Studies ,Genetic Predisposition to Disease ,Heterozygote ,Humans ,Interview ,Psychological ,Male ,Prevalence ,Risk Factors ,Severity of Illness Index ,IMAGINE-ID Consortium ,Copy Number Variants ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
ObjectiveCertain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.MethodsThis international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.ResultsThe four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.ConclusionsMany CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
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- 2021
6. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
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Satterstrom, F Kyle, Kosmicki, Jack A, Wang, Jiebiao, Breen, Michael S, De Rubeis, Silvia, An, Joon-Yong, Peng, Minshi, Collins, Ryan, Grove, Jakob, Klei, Lambertus, Stevens, Christine, Reichert, Jennifer, Mulhern, Maureen S, Artomov, Mykyta, Gerges, Sherif, Sheppard, Brooke, Xu, Xinyi, Bhaduri, Aparna, Norman, Utku, Brand, Harrison, Schwartz, Grace, Nguyen, Rachel, Guerrero, Elizabeth E, Dias, Caroline, Consortium, Autism Sequencing, Aleksic, Branko, Anney, Richard, Barbosa, Mafalda, Bishop, Somer, Brusco, Alfredo, Bybjerg-Grauholm, Jonas, Carracedo, Angel, Chan, Marcus CY, Chiocchetti, Andreas G, Chung, Brian HY, Coon, Hilary, Cuccaro, Michael L, Curró, Aurora, Bernardina, Bernardo Dalla, Doan, Ryan, Domenici, Enrico, Dong, Shan, Fallerini, Chiara, Fernández-Prieto, Montserrat, Ferrero, Giovanni Battista, Freitag, Christine M, Fromer, Menachem, Gargus, J Jay, Geschwind, Daniel, Giorgio, Elisa, González-Peñas, Javier, Guter, Stephen, Halpern, Danielle, Hansen-Kiss, Emily, He, Xin, Herman, Gail E, Hertz-Picciotto, Irva, Hougaard, David M, Hultman, Christina M, Ionita-Laza, Iuliana, Jacob, Suma, Jamison, Jesslyn, Jugessur, Astanand, Kaartinen, Miia, Knudsen, Gun Peggy, Kolevzon, Alexander, Kushima, Itaru, Lee, So Lun, Lehtimäki, Terho, Lim, Elaine T, Lintas, Carla, Lipkin, W Ian, Lopergolo, Diego, Lopes, Fátima, Ludena, Yunin, Maciel, Patricia, Magnus, Per, Mahjani, Behrang, Maltman, Nell, Manoach, Dara S, Meiri, Gal, Menashe, Idan, Miller, Judith, Minshew, Nancy, Montenegro, Eduarda MS, Moreira, Danielle, Morrow, Eric M, Mors, Ole, Mortensen, Preben Bo, Mosconi, Matthew, Muglia, Pierandrea, Neale, Benjamin M, Nordentoft, Merete, Ozaki, Norio, Palotie, Aarno, Parellada, Mara, Passos-Bueno, Maria Rita, Pericak-Vance, Margaret, Persico, Antonio M, and Pessah, Isaac
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Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Genetics ,Brain Disorders ,Mental Health ,Pediatric ,Human Genome ,Clinical Research ,Autism ,Intellectual and Developmental Disabilities (IDD) ,Neurosciences ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Neurological ,Autistic Disorder ,Case-Control Studies ,Cell Lineage ,Cerebral Cortex ,Cohort Studies ,Exome ,Female ,Gene Expression Regulation ,Developmental ,Gene Frequency ,Genetic Predisposition to Disease ,Humans ,Male ,Mutation ,Missense ,Neurobiology ,Neurons ,Phenotype ,Sex Factors ,Single-Cell Analysis ,Exome Sequencing ,Autism Sequencing Consortium ,iPSYCH-Broad Consortium ,autism spectrum disorder ,cell type ,cytoskeleton ,excitatory neurons ,excitatory-inhibitory balance ,exome sequencing ,genetics ,inhibitory neurons ,liability ,neurodevelopment ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
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- 2020
7. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
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Consortium, Cross-Disorder Group of the Psychiatric Genomics, Lee, Phil H, Anttila, Verneri, Won, Hyejung, Feng, Yen-Chen A, Rosenthal, Jacob, Zhu, Zhaozhong, Tucker-Drob, Elliot M, Nivard, Michel G, Grotzinger, Andrew D, Posthuma, Danielle, Wang, Meg M-J, Yu, Dongmei, Stahl, Eli A, Walters, Raymond K, Anney, Richard JL, Duncan, Laramie E, Ge, Tian, Adolfsson, Rolf, Banaschewski, Tobias, Belangero, Sintia, Cook, Edwin H, Coppola, Giovanni, Derks, Eske M, Hoekstra, Pieter J, Kaprio, Jaakko, Keski-Rahkonen, Anna, Kirov, George, Kranzler, Henry R, Luykx, Jurjen J, Rohde, Luis A, Zai, Clement C, Agerbo, Esben, Arranz, MJ, Asherson, Philip, Bækvad-Hansen, Marie, Baldursson, Gísli, Bellgrove, Mark, Belliveau, Richard A, Buitelaar, Jan, Burton, Christie L, Bybjerg-Grauholm, Jonas, Casas, Miquel, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Søren, Demontis, Ditte, Doyle, Alysa E, Dumont, Ashley, Elia, Josephine, Grove, Jakob, Gudmundsson, Olafur O, Haavik, Jan, Hakonarson, Hakon, Hansen, Christine S, Hartman, Catharina A, Hawi, Ziarih, Hervás, Amaia, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Leung, Patrick WL, Loo, Sandra K, Martin, Joanna, Martin, Alicia R, McGough, James J, Medland, Sarah E, Moran, Jennifer L, Mors, Ole, Mortensen, Preben B, Oades, Robert D, Palmer, Duncan S, Pedersen, Carsten B, Pedersen, Marianne G, Peters, Triinu, Poterba, Timothy, Poulsen, Jesper B, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Satterstrom, F Kyle, Schachar, Russell, Artigas, Maria Soler, Steinberg, Stacy, Stefansson, Hreinn, Turley, Patrick, Walters, G Bragi, Team, 23andMe Research, Werge, Thomas, Zayats, Tetyana, and Arking, Dan E
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Neurosciences ,Serious Mental Illness ,Human Genome ,Schizophrenia ,Intellectual and Developmental Disabilities (IDD) ,Brain Disorders ,Genetics ,Pediatric ,Mental Health ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Genetic Pleiotropy ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Mental Disorders ,Neurogenesis ,Quantitative Trait Loci ,Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu ,Cross-Disorder Group of the Psychiatric Genomics Consortium ,GWAS ,Psychiatric genetics ,cross-disorder genetics ,functional genomics ,gene expression ,genetic architecture ,genetic correlation ,neurodevelopment ,pleiotropy ,psychiatric disorders ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
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- 2019
8. Investigating Direct and Indirect Genetic Effects in Attention-Deficit/Hyperactivity Disorder Using Parent-Offspring Trios
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Martin, Joanna, Wray, Matthew, Agha, Sharifah Shameem, Lewis, Katie J.S., Anney, Richard J.L., O’Donovan, Michael C., Thapar, Anita, and Langley, Kate
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- 2023
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9. Genetic common variants associated with cerebellar volume and their overlap with mental disorders: a study on 33,265 individuals from the UK-Biobank
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Chambers, Tom, Escott-Price, Valentina, Legge, Sophie, Baker, Emily, Singh, Krish D., Walters, James T. R., Caseras, Xavier, and Anney, Richard J. L.
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- 2022
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10. Identification of common genetic risk variants for autism spectrum disorder
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Grove, Jakob, Ripke, Stephan, Als, Thomas D, Mattheisen, Manuel, Walters, Raymond K, Won, Hyejung, Pallesen, Jonatan, Agerbo, Esben, Andreassen, Ole A, Anney, Richard, Awashti, Swapnil, Belliveau, Rich, Bettella, Francesco, Buxbaum, Joseph D, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Christensen, Jane H, Churchhouse, Claire, Dellenvall, Karin, Demontis, Ditte, De Rubeis, Silvia, Devlin, Bernie, Djurovic, Srdjan, Dumont, Ashley L, Goldstein, Jacqueline I, Hansen, Christine S, Hauberg, Mads Engel, Hollegaard, Mads V, Hope, Sigrun, Howrigan, Daniel P, Huang, Hailiang, Hultman, Christina M, Klei, Lambertus, Maller, Julian, Martin, Joanna, Martin, Alicia R, Moran, Jennifer L, Nyegaard, Mette, Nærland, Terje, Palmer, Duncan S, Palotie, Aarno, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, dPoterba, Timothy, Poulsen, Jesper Buchhave, Pourcain, Beate St, Qvist, Per, Rehnström, Karola, Reichenberg, Abraham, Reichert, Jennifer, Robinson, Elise B, Roeder, Kathryn, Roussos, Panos, Saemundsen, Evald, Sandin, Sven, Satterstrom, F Kyle, Davey Smith, George, Stefansson, Hreinn, Steinberg, Stacy, Stevens, Christine R, Sullivan, Patrick F, Turley, Patrick, Walters, G Bragi, Xu, Xinyi, Stefansson, Kari, Geschwind, Daniel H, Nordentoft, Merete, Hougaard, David M, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Neale, Benjamin M, Daly, Mark J, and Børglum, Anders D
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Intellectual and Developmental Disabilities (IDD) ,Human Genome ,Pediatric ,Brain Disorders ,Autism ,Biotechnology ,Genetics ,Mental Health ,Prevention ,2.3 Psychological ,social and economic factors ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Adolescent ,Autism Spectrum Disorder ,Case-Control Studies ,Child ,Child ,Preschool ,Denmark ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Male ,Multifactorial Inheritance ,Phenotype ,Polymorphism ,Single Nucleotide ,Risk Factors ,Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium ,BUPGEN ,Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ,23andMe Research Team ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
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- 2019
11. Motivation and Cognitive Abilities as Mediators Between Polygenic Scores and Psychopathology in Children
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Pat, Narun, Riglin, Lucy, Anney, Richard, Wang, Yue, Barch, Deanna M., Thapar, Anita, and Stringaris, Argyris
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- 2022
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12. Sleep disturbances in ADHD: investigating the contribution of polygenic liability for ADHD and sleep-related phenotypes
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Lewis, Katie J. S., Martin, Joanna, Gregory, Alice M., Anney, Richard, Thapar, Anita, and Langley, Kate
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- 2022
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13. The antecedents and outcomes of persistent and remitting adolescent depressive symptom trajectories: a longitudinal, population-based English study
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Weavers, Bryony, Heron, Jon, Thapar, Ajay K, Stephens, Alice, Lennon, Jessica, Bevan Jones, Rhys, Eyre, Olga, Anney, Richard JL, Collishaw, Stephan, Thapar, Anita, and Rice, Frances
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- 2021
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14. Cis-effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders
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Hall, Lynsey S., Pain, Oliver, O’Brien, Heath E., Anney, Richard, Walters, James T. R., Owen, Michael J., O’Donovan, Michael C., and Bray, Nicholas J.
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- 2021
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15. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
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Weiner, Daniel J, Wigdor, Emilie M, Ripke, Stephan, Walters, Raymond K, Kosmicki, Jack A, Grove, Jakob, Samocha, Kaitlin E, Goldstein, Jacqueline I, Okbay, Aysu, Bybjerg-Grauholm, Jonas, Werge, Thomas, Hougaard, David M, Taylor, Jacob, Skuse, David, Devlin, Bernie, Anney, Richard, Sanders, Stephan J, Bishop, Somer, Mortensen, Preben Bo, Børglum, Anders D, Smith, George Davey, Daly, Mark J, and Robinson, Elise B
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Biological Sciences ,Genetics ,Autism ,Brain Disorders ,Prevention ,Mental Health ,Pediatric ,Intellectual and Developmental Disabilities (IDD) ,2.4 Surveillance and distribution ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Good Health and Well Being ,Adult ,Autism Spectrum Disorder ,Child ,Cohort Studies ,Educational Status ,Ethnicity ,Family Health ,Female ,Genetic Association Studies ,Genetic Predisposition to Disease ,Genetic Variation ,Genetics ,Behavioral ,Humans ,Intellectual Disability ,Intelligence ,Male ,Multifactorial Inheritance ,Phenotype ,Risk Factors ,Schizophrenia ,Sequence Deletion ,iPSYCH-Broad Autism Group ,Psychiatric Genomics Consortium Autism Group ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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- 2017
16. Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: a GWAS meta-analysis
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Powell, Victoria, Martin, Joanna, Thapar, Anita, Rice, Frances, and Anney, Richard J. L.
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- 2021
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17. Corrigendum to “Characterising depression trajectories in young people at high familial risk of depression” [J. Affect. Disord. 337 (2023) 66–74 (15 September)]
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Weavers, Bryony, primary, Riglin, Lucy, additional, Martin, Joanna, additional, Anney, Richard, additional, Collishaw, Stephan, additional, Heron, Jon, additional, Thapar, Ajay, additional, Thapar, Anita, additional, and Rice, Frances, additional
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- 2023
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18. What explains the link between childhood ADHD and adolescent depression? Investigating the role of peer relationships and academic attainment
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Powell, Victoria, Riglin, Lucy, Hammerton, Gemma, Eyre, Olga, Martin, Joanna, Anney, Richard, Thapar, Anita, and Rice, Frances
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- 2020
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19. Using Genetics to Examine a General Liability to Childhood Psychopathology
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Riglin, Lucy, Thapar, Ajay K., Leppert, Beate, Martin, Joanna, Richards, Alexander, Anney, Richard, Davey Smith, George, Tilling, Kate, Stergiakouli, Evie, Lahey, Benjamin B., O’Donovan, Michael C., Collishaw, Stephan, and Thapar, Anita
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- 2020
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20. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
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O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Parikshak, Neelroop N, Newhouse, Stephen, Ripke, Stephan, Neale, Benjamin M, Purcell, Shaun M, Posthuma, Danielle, Nurnberger, John I, Lee, S Hong, Faraone, Stephen V, Perlis, Roy H, Mowry, Bryan J, Thapar, Anita, Goddard, Michael E, Witte, John S, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan E, Asherson, Philip, Azevedo, Maria H, Backlund, Lena, Badner, Judith A, Bailey, Anthony J, Banaschewski, Tobias, Barchas, Jack D, Barnes, Michael R, Barrett, Thomas B, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayes, Monica, Bellivier, Frank, Bergen, Sarah E, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B, Black, Donald W, Blackwood, Douglas HR, Bloss, Cinnamon S, Boehnke, Michael, Boomsma, Dorret I, Breuer, Rene, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy G, Buitelaar, Jan K, Bunney, William E, Buxbaum, Joseph D, Byerley, William F, Byrne, Enda M, Caesar, Sian, Cahn, Wiepke, Cantor, Rita M, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Mattheisen, Manuel, Cloninger, C Robert, Collier, David A, Cook, Edwin H, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William H, Craig, David W, Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary J, Doyle, Alysa E, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard P, Edenberg, Howard J, Elia, Josephine, Ennis, Sean, Etain, Bruno, and Fanous, Ayman
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Human Genome ,Brain Disorders ,Serious Mental Illness ,Schizophrenia ,Genetics ,Depression ,Mental Health ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Good Health and Well Being ,Brain ,Databases ,Genetic ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Histones ,Humans ,Mental Disorders ,Signal Transduction ,Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium ,Neurosciences ,Psychology ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
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- 2015
21. Novel Insight Into the Etiology of Autism Spectrum Disorder Gained by Integrating Expression Data With Genome-wide Association Statistics
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Pain, Oliver, Pocklington, Andrew J., Holmans, Peter A., Bray, Nicholas J., O’Brien, Heath E., Hall, Lynsey S., Pardiñas, Antonio F., O’Donovan, Michael C., Owen, Michael J., and Anney, Richard
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- 2019
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22. Evidence of Assortative Mating in Autism Spectrum Disorder
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Connolly, Siobhan, Anney, Richard, Gallagher, Louise, and Heron, Elizabeth A.
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- 2019
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23. Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway
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Nicodemus, Kristin K, Hargreaves, April, Morris, Derek, Anney, Richard, Gill, Michael, Corvin, Aiden, and Donohoe, Gary
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Mental Health ,Schizophrenia ,Serious Mental Illness ,Genetics ,Clinical Research ,Behavioral and Social Science ,Neurosciences ,Brain Disorders ,Prevention ,2.3 Psychological ,social and economic factors ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Adult ,Cognition Disorders ,Epistasis ,Genetic ,Female ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Male ,Memory ,Short-Term ,Middle Aged ,Multifactorial Inheritance ,Neural Pathways ,Neuropsychological Tests ,Polymorphism ,Single Nucleotide ,Psychotic Disorders ,Zinc Fingers ,Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium ,Wellcome Trust Case Control Consortium 2 ,Other Medical and Health Sciences ,Psychology ,Cognitive Sciences - Abstract
ImportanceWe investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained.ObjectivesTo (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score.Design, setting, and participantsPatients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis).Main outcomes and measuresParticipants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition.ResultsHigher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants.Conclusions and relevanceThese data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.
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- 2014
24. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders
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Pinto, Dalila, Delaby, Elsa, Merico, Daniele, Barbosa, Mafalda, Merikangas, Alison, Klei, Lambertus, Thiruvahindrapuram, Bhooma, Xu, Xiao, Ziman, Robert, Wang, Zhuozhi, Vorstman, Jacob AS, Thompson, Ann, Regan, Regina, Pilorge, Marion, Pellecchia, Giovanna, Pagnamenta, Alistair T, Oliveira, Bárbara, Marshall, Christian R, Magalhaes, Tiago R, Lowe, Jennifer K, Howe, Jennifer L, Griswold, Anthony J, Gilbert, John, Duketis, Eftichia, Dombroski, Beth A, De Jonge, Maretha V, Cuccaro, Michael, Crawford, Emily L, Correia, Catarina T, Conroy, Judith, Conceição, Inês C, Chiocchetti, Andreas G, Casey, Jillian P, Cai, Guiqing, Cabrol, Christelle, Bolshakova, Nadia, Bacchelli, Elena, Anney, Richard, Gallinger, Steven, Cotterchio, Michelle, Casey, Graham, Zwaigenbaum, Lonnie, Wittemeyer, Kerstin, Wing, Kirsty, Wallace, Simon, van Engeland, Herman, Tryfon, Ana, Thomson, Susanne, Soorya, Latha, Rogé, Bernadette, Roberts, Wendy, Poustka, Fritz, Mouga, Susana, Minshew, Nancy, McInnes, L Alison, McGrew, Susan G, Lord, Catherine, Leboyer, Marion, Le Couteur, Ann S, Kolevzon, Alexander, González, Patricia Jiménez, Jacob, Suma, Holt, Richard, Guter, Stephen, Green, Jonathan, Green, Andrew, Gillberg, Christopher, Fernandez, Bridget A, Duque, Frederico, Delorme, Richard, Dawson, Geraldine, Chaste, Pauline, Café, Cátia, Brennan, Sean, Bourgeron, Thomas, Bolton, Patrick F, Bölte, Sven, Bernier, Raphael, Baird, Gillian, Bailey, Anthony J, Anagnostou, Evdokia, Almeida, Joana, Wijsman, Ellen M, Vieland, Veronica J, Vicente, Astrid M, Schellenberg, Gerard D, Pericak-Vance, Margaret, Paterson, Andrew D, Parr, Jeremy R, Oliveira, Guiomar, Nurnberger, John I, Monaco, Anthony P, Maestrini, Elena, Klauck, Sabine M, Hakonarson, Hakon, Haines, Jonathan L, Geschwind, Daniel H, Freitag, Christine M, Folstein, Susan E, and Ennis, Sean
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Genetics ,Brain Disorders ,Pediatric ,Mental Health ,Intellectual and Developmental Disabilities (IDD) ,Neurosciences ,Autism ,2.1 Biological and endogenous factors ,Aetiology ,Child ,Child Development Disorders ,Pervasive ,DNA Copy Number Variations ,Female ,Gene Regulatory Networks ,Humans ,Male ,Metabolic Networks and Pathways ,Multigene Family ,Pedigree ,Sequence Deletion ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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- 2014
25. The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses
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Buxbaum, Joseph D, Bolshakova, Nadia, Brownfeld, Jessica M, Anney, Richard JL, Bender, Patrick, Bernier, Raphael, Cook, Edwin H, Coon, Hilary, Cuccaro, Michael, Freitag, Christine M, Hallmayer, Joachim, Geschwind, Daniel, Klauck, Sabine M, Nurnberger, John I, Oliveira, Guiomar, Pinto, Dalila, Poustka, Fritz, Scherer, Stephen W, Shih, Andy, Sutcliffe, James S, Szatmari, Peter, Vicente, Astrid M, Vieland, Veronica, and Gallagher, Louise
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Intellectual and Developmental Disabilities (IDD) ,Clinical Research ,Brain Disorders ,Pediatric ,Autism ,Mental Health ,Genetics ,Behavioral and Social Science ,Human Genome ,Mental health ,Good Health and Well Being ,Clinical Sciences ,Neurosciences - Abstract
BackgroundThere is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD.MethodsIn a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year program to collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center.ResultsOver 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children's or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the focus is on sequencing complete trios. ASC sequencing for the first 1,000 samples (all from whole-blood DNA) is complete and data will be released in 2014. Data is being made available through NIH databases (database of Genotypes and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA released in Dist 11.0. Primary funding for the collection, genotyping, sequencing and distribution of TASC samples was provided by Autism Speaks and the NIH, including the National Institute of Mental Health (NIMH) and the National Human Genetics Research Institute (NHGRI).ConclusionsTASC represents an important sample set that leverages expert sites. Similar approaches, leveraging expert sites and ongoing studies, represent an important path towards further enhancing available ASD samples.
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- 2014
26. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.
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Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan, Asherson, Philip, Azevedo, Maria, Backlund, Lena, Badner, Judith, Bailey, Anthony, Banaschewski, Tobias, Barchas, Jack, Barnes, Michael, Barrett, Thomas, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayés, Mònica, Bellivier, Frank, Bergen, Sarah, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth, Black, Donald, Blackwood, Douglas, Boehnke, Michael, Boomsma, Dorret, Breen, Gerome, Breuer, René, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy, Buitelaar, Jan, Bunney, William, Buxbaum, Joseph, Byerley, William, Byrne, Enda, Caesar, Sian, Cahn, Wiepke, Cantor, Rita, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Cloninger, C, Collier, David, Cook, Edwin, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William, Craig, David, Craig, Ian, Crosbie, Jennifer, Cuccaro, Michael, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary, Doyle, Alysa, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard, Edenberg, Howard, Elia, Josephine, Ennis, Sean, Etain, Bruno, Fanous, Ayman, Farmer, Anne, Ferrier, I, Flickinger, Matthew, Fombonne, Eric, Foroud, Tatiana, Frank, Josef, Franke, Barbara, Fraser, Christine, Freedman, Robert, Giegling, Ina, Gill, Michael, Gordon, Scott, Gordon-Smith, Katherine, Green, Elaine, Greenwood, Tiffany, Grice, Dorothy, Gross, Magdalena, Grozeva, Detelina, and Guan, Weihua
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Adult ,Attention Deficit Disorder with Hyperactivity ,Bipolar Disorder ,Child ,Child Development Disorders ,Pervasive ,Crohn Disease ,Depressive Disorder ,Major ,Genetic Heterogeneity ,Genetic Predisposition to Disease ,Genome ,Human ,Genome-Wide Association Study ,Humans ,Inheritance Patterns ,Mental Disorders ,Polymorphism ,Single Nucleotide ,Schizophrenia - Abstract
Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohns disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
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- 2013
27. The role of rare compound heterozygous events in autism spectrum disorder
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Lin, Bochao Danae, Colas, Fabrice, Nijman, Isaac J., Medic, Jelena, Brands, William, Parr, Jeremy R., van Eijk, Kristel R., Klauck, Sabine M., Chiocchetti, Andreas G., Freitag, Christine M., Maestrini, Elena, Bacchelli, Elena, Coon, Hilary, Vicente, Astrid, Oliveira, Guiomar, Pagnamenta, Alistair T., Gallagher, Louise, Ennis, Sean, Anney, Richard, Bourgeron, Thomas, Luykx, Jurjen J., and Vorstman, Jacob
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- 2020
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28. High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression
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Hamshere, Marian L, Langley, Kate, Martin, Joanna, Agha, Sharifah Shameem, Stergiakouli, Evangelia, Anney, Richard JL, Buitelaar, Jan, Faraone, Stephen V, Lesch, Klaus-Peter, Neale, Benjamin M, Franke, Barbara, Sonuga-Barke, Edmund, Asherson, Philip, Merwood, Andrew, Kuntsi, Jonna, Medland, Sarah E, Ripke, Stephan, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J, Romanos, Marcel, Romanos, Jasmin, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Roeyers, Herbert, Biederman, Joseph, Doyle, Alysa E, Hakonarson, Hakon, Rothenberger, Aribert, Banaschewski, Tobias, Oades, Robert D, McGough, James J, Kent, Lindsey, Williams, Nigel, Owen, Michael J, Holmans, Peter, O’Donovan, Michael C, and Thapar, Anita
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Prevention ,Behavioral and Social Science ,Human Genome ,Genetics ,Mental Health ,Attention Deficit Hyperactivity Disorder (ADHD) ,Clinical Research ,Brain Disorders ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Aggression ,Anxiety Disorders ,Attention Deficit Disorder with Hyperactivity ,Child ,Child ,Preschool ,Comorbidity ,Conduct Disorder ,Depressive Disorder ,Female ,Genetic Predisposition to Disease ,Genetic Variation ,Humans ,Male ,Multifactorial Inheritance ,United Kingdom ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.
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- 2013
29. Individual common variants exert weak effects on the risk for autism spectrum disorders
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Anney, Richard, Klei, Lambertus, Pinto, Dalila, Almeida, Joana, Bacchelli, Elena, Baird, Gillian, Bolshakova, Nadia, Bölte, Sven, Bolton, Patrick F, Bourgeron, Thomas, Brennan, Sean, Brian, Jessica, Casey, Jillian, Conroy, Judith, Correia, Catarina, Corsello, Christina, Crawford, Emily L, de Jonge, Maretha, Delorme, Richard, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A, Folstein, Susan E, Fombonne, Eric, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T, Green, Andrew, Green, Jonathan, Guter, Stephen J, Heron, Elizabeth A, Holt, Richard, Howe, Jennifer L, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Jacob, Suma, Kenny, Graham P, Kim, Cecilia, Kolevzon, Alexander, Kustanovich, Vlad, Lajonchere, Clara M, Lamb, Janine A, Law-Smith, Miriam, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L, Liu, Xiao-Qing, Lombard, Frances, Lord, Catherine, Lotspeich, Linda, Lund, Sabata C, Magalhaes, Tiago R, Mantoulan, Carine, McDougle, Christopher J, Melhem, Nadine M, Merikangas, Alison, Minshew, Nancy J, Mirza, Ghazala K, Munson, Jeff, Noakes, Carolyn, Nygren, Gudrun, Papanikolaou, Katerina, Pagnamenta, Alistair T, Parrini, Barbara, Paton, Tara, Pickles, Andrew, Posey, David J, Poustka, Fritz, Ragoussis, Jiannis, Regan, Regina, Roberts, Wendy, Roeder, Kathryn, Roge, Bernadette, Rutter, Michael L, Schlitt, Sabine, Shah, Naisha, Sheffield, Val C, Soorya, Latha, Sousa, Inês, Stoppioni, Vera, Sykes, Nuala, Tancredi, Raffaella, Thompson, Ann P, Thomson, Susanne, Tryfon, Ana, Tsiantis, John, Van Engeland, Herman, Vincent, John B, Volkmar, Fred, Vorstman, JAS, Wallace, Simon, Wing, Kirsty, Wittemeyer, Kerstin, Wood, Shawn, Zurawiecki, Danielle, Zwaigenbaum, Lonnie, and Bailey, Anthony J
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Behavioral and Social Science ,Clinical Research ,Human Genome ,Mental Health ,Genetics ,Brain Disorders ,Pediatric ,Intellectual and Developmental Disabilities (IDD) ,Autism ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Alleles ,Child ,Child Development Disorders ,Pervasive ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Language Development ,Male ,Membrane Proteins ,Nerve Tissue Proteins ,Polymorphism ,Single Nucleotide ,Risk Factors ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
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- 2012
30. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder
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Casey, Jillian P, Magalhaes, Tiago, Conroy, Judith M, Regan, Regina, Shah, Naisha, Anney, Richard, Shields, Denis C, Abrahams, Brett S, Almeida, Joana, Bacchelli, Elena, Bailey, Anthony J, Baird, Gillian, Battaglia, Agatino, Berney, Tom, Bolshakova, Nadia, Bolton, Patrick F, Bourgeron, Thomas, Brennan, Sean, Cali, Phil, Correia, Catarina, Corsello, Christina, Coutanche, Marc, Dawson, Geraldine, de Jonge, Maretha, Delorme, Richard, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A, Folstein, Susan E, Foley, Suzanne, Fombonne, Eric, Freitag, Christine M, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T, Green, Jonathan, Guter, Stephen J, Hakonarson, Hakon, Holt, Richard, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Kim, Cecilia, Klauck, Sabine M, Kolevzon, Alexander, Lamb, Janine A, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L, Lord, Catherine, Lund, Sabata C, Maestrini, Elena, Mantoulan, Carine, Marshall, Christian R, McConachie, Helen, McDougle, Christopher J, McGrath, Jane, McMahon, William M, Merikangas, Alison, Miller, Judith, Minopoli, Fiorella, Mirza, Ghazala K, Munson, Jeff, Nelson, Stanley F, Nygren, Gudrun, Oliveira, Guiomar, Pagnamenta, Alistair T, Papanikolaou, Katerina, Parr, Jeremy R, Parrini, Barbara, Pickles, Andrew, Pinto, Dalila, Piven, Joseph, Posey, David J, Poustka, Annemarie, Poustka, Fritz, Ragoussis, Jiannis, Roge, Bernadette, Rutter, Michael L, Sequeira, Ana F, Soorya, Latha, Sousa, Inês, Sykes, Nuala, Stoppioni, Vera, Tancredi, Raffaella, Tauber, Maïté, Thompson, Ann P, Thomson, Susanne, Tsiantis, John, Van Engeland, Herman, Vincent, John B, Volkmar, Fred, Vorstman, Jacob AS, Wallace, Simon, Wang, Kai, Wassink, Thomas H, White, Kathy, and Wing, Kirsty
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Autism ,Genetics ,Mental Health ,Intellectual and Developmental Disabilities (IDD) ,Brain Disorders ,Biotechnology ,Pediatric ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Adult ,Child ,Child Development Disorders ,Pervasive ,Cluster Analysis ,Cohort Studies ,DNA Copy Number Variations ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Haplotypes ,Homozygote ,Humans ,Linkage Disequilibrium ,Male ,Middle Aged ,Nuclear Family ,Polymorphism ,Single Nucleotide ,Complementary and Alternative Medicine ,Paediatrics and Reproductive Medicine ,Genetics & Heredity - Abstract
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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- 2012
31. Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3
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Williams, Nigel M, Franke, Barbara, Mick, Eric, Anney, Richard JL, Freitag, Christine M, Gill, Michael, Thapar, Anita, O'Donovan, Michael C, Owen, Michael J, Holmans, Peter, Kent, Lindsey, Middleton, Frank, Zhang-James, Yanli, Liu, Lu, Meyer, Jobst, Nguyen, Thuy Trang, Romanos, Jasmin, Romanos, Marcel, Seitz, Christiane, Renner, Tobias J, Walitza, Susanne, Warnke, Andreas, Palmason, Haukur, Buitelaar, Jan, Rommelse, Nanda, Vasquez, Alejandro Arias, Hawi, Ziarih, Langley, Kate, Sergeant, Joseph, Steinhausen, Hans-Christoph, Roeyers, Herbert, Biederman, Joseph, Zaharieva, Irina, Hakonarson, Hakon, Elia, Josephine, Lionel, Anath C, Crosbie, Jennifer, Marshall, Christian R, Schachar, Russell, Scherer, Stephen W, Todorov, Alexandre, Smalley, Susan L, Loo, Sandra, Nelson, Stanley, Shtir, Corina, Asherson, Philip, Reif, Andreas, Lesch, Klaus-Peter, and Faraone, Stephen V
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Human Genome ,Clinical Research ,Mental Health ,Genetics ,Pediatric ,Attention Deficit Hyperactivity Disorder (ADHD) ,Brain Disorders ,Serious Mental Illness ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Attention Deficit Disorder with Hyperactivity ,Canada ,Causality ,Child ,Child ,Preschool ,Female ,Gene Dosage ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,In Situ Hybridization ,Fluorescence ,Inheritance Patterns ,Polymorphism ,Single Nucleotide ,Receptors ,Nicotinic ,Segmental Duplications ,Genomic ,United Kingdom ,United States ,alpha7 Nicotinic Acetylcholine Receptor ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
ObjectiveAttention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology.MethodThe authors performed a genome-wide analysis of large, rare CNVs (100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder.ConclusionsThese findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.
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- 2012
32. Polygenic risk for schizophrenia and subcortical brain anatomy in the UK Biobank cohort
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Grama, Steluta, Willcocks, Isabella, Hubert, John J., Pardiñas, Antonio F., Legge, Sophie E., Bracher-Smith, Matthew, Menzies, Georgina E., Hall, Lynsey S., Pocklington, Andrew J., Anney, Richard J. L., Bray, Nicholas J., Escott-Price, Valentina, and Caseras, Xavier
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- 2020
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33. A genome-wide scan for common alleles affecting risk for autism
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Anney, Richard, Klei, Lambertus, Pinto, Dalila, Regan, Regina, Conroy, Judith, Magalhaes, Tiago R, Correia, Catarina, Abrahams, Brett S, Sykes, Nuala, Pagnamenta, Alistair T, Almeida, Joana, Bacchelli, Elena, Bailey, Anthony J, Baird, Gillian, Battaglia, Agatino, Berney, Tom, Bolshakova, Nadia, Bölte, Sven, Bolton, Patrick F, Bourgeron, Thomas, Brennan, Sean, Brian, Jessica, Carson, Andrew R, Casallo, Guillermo, Casey, Jillian, Chu, Su H, Cochrane, Lynne, Corsello, Christina, Crawford, Emily L, Crossett, Andrew, Dawson, Geraldine, de Jonge, Maretha, Delorme, Richard, Drmic, Irene, Duketis, Eftichia, Duque, Frederico, Estes, Annette, Farrar, Penny, Fernandez, Bridget A, Folstein, Susan E, Fombonne, Eric, Freitag, Christine M, Gilbert, John, Gillberg, Christopher, Glessner, Joseph T, Goldberg, Jeremy, Green, Jonathan, Guter, Stephen J, Hakonarson, Hakon, Heron, Elizabeth A, Hill, Matthew, Holt, Richard, Howe, Jennifer L, Hughes, Gillian, Hus, Vanessa, Igliozzi, Roberta, Kim, Cecilia, Klauck, Sabine M, Kolevzon, Alexander, Korvatska, Olena, Kustanovich, Vlad, Lajonchere, Clara M, Lamb, Janine A, Laskawiec, Magdalena, Leboyer, Marion, Le Couteur, Ann, Leventhal, Bennett L, Lionel, Anath C, Liu, Xiao-Qing, Lord, Catherine, Lotspeich, Linda, Lund, Sabata C, Maestrini, Elena, Mahoney, William, Mantoulan, Carine, Marshall, Christian R, McConachie, Helen, McDougle, Christopher J, McGrath, Jane, McMahon, William M, Melhem, Nadine M, Merikangas, Alison, Migita, Ohsuke, Minshew, Nancy J, Mirza, Ghazala K, Munson, Jeff, Nelson, Stanley F, Noakes, Carolyn, Noor, Abdul, Nygren, Gudrun, Oliveira, Guiomar, Papanikolaou, Katerina, Parr, Jeremy R, Parrini, Barbara, Paton, Tara, Pickles, Andrew, Piven, Joseph, Posey, David J, Poustka, Annemarie, and Poustka, Fritz
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Clinical Research ,Human Genome ,Mental Health ,Genetics ,Brain Disorders ,Pediatric ,Biotechnology ,Intellectual and Developmental Disabilities (IDD) ,Autism ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Alleles ,Autistic Disorder ,DNA Copy Number Variations ,Databases ,Genetic ,Genetic Predisposition to Disease ,Genetic Variation ,Genome ,Human ,Genome-Wide Association Study ,Genotype ,Humans ,Polymorphism ,Single Nucleotide ,Risk Factors ,White People ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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- 2010
34. DRAGON-Data: a platform and protocol for integrating genomic and phenotypic data across large psychiatric cohorts
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Lynham, Amy J., primary, Knott, Sarah, additional, Underwood, Jack F. G., additional, Hubbard, Leon, additional, Agha, Sharifah S., additional, Bisson, Jonathan I., additional, van den Bree, Marianne B. M., additional, Chawner, Samuel J. R. A., additional, Craddock, Nicholas, additional, O'Donovan, Michael, additional, Jones, Ian R., additional, Kirov, George, additional, Langley, Kate, additional, Martin, Joanna, additional, Rice, Frances, additional, Roberts, Neil P., additional, Thapar, Anita, additional, Anney, Richard, additional, Owen, Michael J., additional, Hall, Jeremy, additional, Pardiñas, Antonio F., additional, and Walters, James T. R., additional
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- 2023
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35. Sleep disturbances in ADHD: investigating the contribution of polygenic liability for ADHD and sleep-related phenotypes.
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Lewis, Katie J. S., Martin, Joanna, Gregory, Alice M., Anney, Richard, Thapar, Anita, and Langley, Kate
- Subjects
ATTENTION-deficit hyperactivity disorder ,SLEEP disorders ,RESEARCH funding ,PHENOTYPES ,COMORBIDITY - Abstract
Sleep disturbances are common in attention deficit hyperactivity disorder (ADHD) and associated with poor outcomes. We tested whether, in children with ADHD, (1) polygenic liability for sleep phenotypes is over- or under-transmitted from parents, (2) this liability is linked to comorbid sleep disturbances, and (3) ADHD genetic risk is associated with comorbid sleep disturbances. We derived polygenic scores (PGS) for insomnia, chronotype, sleep duration, and ADHD, in 758 children (5–18 years old) diagnosed with ADHD and their parents. We conducted polygenic transmission disequilibrium tests for each sleep PGS in complete parent–offspring ADHD trios (N = 328) and an independent replication sample of ADHD trios (N = 844). Next, we tested whether insomnia, sleep duration, and ADHD PGS were associated with co-occurring sleep phenotypes (hypersomnia, insomnia, restless sleep, poor sleep quality, and nightmares) in children with ADHD. Children's insomnia and chronotype PGS did not differ from mid-parent average PGS but long sleep duration PGS were significantly over-transmitted to children with ADHD. This was supported by a combined analysis using the replication sample. Insomnia, sleep duration, and ADHD PGS were not associated with comorbid sleep disturbances. There is weak evidence that children with ADHD over-inherit polygenic liability for longer sleep duration and do not differentially inherit polygenic liability for insomnia or chronotype. There was insufficient evidence that childhood sleep disturbances were driven by polygenic liability for ADHD or sleep traits, suggesting that sleep disturbances in ADHD may be aetiologically different to general population sleep phenotypes and do not index greater ADHD genetic risk burden. [ABSTRACT FROM AUTHOR]
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- 2023
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36. T7. DOES POLYGENIC RISK FOR AUTISM PREDICT FOR DEPRESSIVE PHENOTYPIC DIFFERENCES ACROSS MENTAL HEALTH CONDITIONS? PRELIMINARY FINDINGS FROM THE DRAGON-DATA REPOSITORY
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Underwood, Jack, primary, Hall, Jeremy, additional, and Anney, Richard, additional
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- 2022
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37. Copy Number Variants increasing risk for schizophrenia: shared and distinct effects on brain morphometry and cognitive performance
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Caseras, Xavier, primary, Legge, Sophie E., additional, Bracher-Smith, Matthew, additional, Anney, Richard, additional, Owen, Michael J., additional, Escott-Price, Valentina, additional, and Kirov, George, additional
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- 2022
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38. T83. GENE-SET POLYGENIC RISK SCORE PREDICTION OF BRAIN PHENOTYPES
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Caseras, Xavier, primary, Pumfrey, Helena, additional, Baker, Emily, additional, Anney, Richard, additional, and Escott-Price, Valentina, additional
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- 2022
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39. SUB-DIAGNOSTIC EFFECTS OF GENETIC VARIANTS ASSOCIATED WITH AUTISM
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Rolland, Thomas, primary, Cliquet, Freddy, additional, Anney, Richard, additional, Moreau, Clara, additional, Huguet, Guillaume, additional, Duan, Jinjie, additional, Warrier, Varun, additional, Børglum, Anders, additional, Grove, Jakob, additional, Baron-Cohen, Simon, additional, Packer, Alan, additional, Chung, Wendy, additional, Jacquemont, Sébastien, additional, Delorme, Richard, additional, and Bourgeron, Thomas, additional
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- 2022
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40. Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p
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Weiner, Daniel J., Ling, Emi, Erdin, Serkan, Tai, Derek J. C., Yadav, Rachita, Grove, Jakob, Fu, Jack M., Nadig, Ajay, Carey, Caitlin E., Baya, Nikolas, Bybjerg-Grauholm, Jonas, Mortensen, Preben B., Werge, Thomas, Demontis, Ditte, Mors, Ole, Nordentoft, Merete, Als, Thomas D., Baekvad-Hansen, Marie, Rosengren, Anders, Havdahl, Alexandra, Hedemand, Anne, Palotie, Aarno, Chakravarti, Aravinda, Arking, Dan, Sulovari, Arvis, Starnawska, Anna, Thiruvahindrapuram, Bhooma, de Leeuw, Christiaan, Carey, Caitlin, Ladd-Acosta, Christine, van der Merwe, Celia, Devlin, Bernie, Cook, Edwin H., Eichler, Evan, Corfield, Elisabeth, Dieleman, Gwen, Schellenberg, Gerard, Hakonarson, Hakon, Coon, Hilary, Dziobek, Isabel, Vorstman, Jacob, Girault, Jessica, Sutcliffe, James S., Duan, Jinjie, Nurnberger, John, Hallmayer, Joachim, Buxbaum, Joseph, Piven, Joseph, Weiss, Lauren, Davis, Lea, Janecka, Magdalena, Mattheisen, Manuel, State, Matthew W., Gill, Michael, Daly, Mark, Uddin, Mohammed, Andreassen, Ole, Szatmari, Peter, Lee, Phil Hyoun, Anney, Richard, Ripke, Stephan, Satterstrom, Kyle, Santangelo, Susan, Kuo, Susan, van Elst, Ludger Tebartz, Rolland, Thomas, Bougeron, Thomas, Polderman, Tinca, Turner, Tychele, Underwood, Jack, Manikandan, Veera, Pillalamarri, Vamsee, Warrier, Varun, Philipsen, Alexandra, Reif, Andreas, Hinney, Anke, Cormand, Bru, Bau, Claiton H. D., Rovaris, Diego Luiz, Sonuga-Barke, Edmund, Corfield, Elizabeth, Grevet, Eugenio Horacio, Salum, Giovanni, Larsson, Henrik, Buitelaar, Jan, Haavik, Jan, McGough, James, Kuntsi, Jonna, Elia, Josephine, Lesch, Klaus-Peter, Klein, Marieke, Bellgrove, Mark, Tesli, Martin, Leung, Patrick W. L., Pan, Pedro M., Dalsgaard, Soren, Loo, Sandra, Medland, Sarah, Faraone, Stephen V., Reichborn-Kjennerud, Ted, Banaschewski, Tobias, Hawi, Ziarih, Berretta, Sabina, Macosko, Evan Z., Sebat, Jonathan, O’Connor, Luke J., Hougaard, David M., Børglum, Anders D., Talkowski, Michael E., McCarroll, Steven A., Robinson, Elise B., Pediatrics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Hinney, Anke (Beitragende*r), Child and Adolescent Psychiatry / Psychology, Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Complex Trait Genetics, and Clinical Developmental Psychology
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Genètica humana ,DNA Copy Number Variations ,Autism ,3112 Neurosciences ,Medizin ,Chromosomes ,Cromosomes ,Human genetics ,Genetics ,Humans ,Autistic Disorder ,Chromosome Deletion ,Chromosomes, Human, Pair 16/genetics ,Autisme ,Chromosomes, Human, Pair 16 ,Autistic Disorder/genetics - Abstract
in press, weitere Verfasser:innen aus Einrichtungen außerhalb der Universität Duisburg-Essen sind nicht aufgeführt. The canonical paradigm for converting genetic association to mechanism involves iteratively mapping individual associations to the proximal genes through which they act. In contrast, in the present study we demonstrate the feasibility of extracting biological insights from a very large region of the genome and leverage this strategy to study the genetic influences on autism. Using a new statistical approach, we identified the 33-Mb p-arm of chromosome 16 (16p) as harboring the greatest excess of autism’s common polygenic influences. The region also includes the mechanistically cryptic and autism-associated 16p11.2 copy number variant. Analysis of RNA-sequencing data revealed that both the common polygenic influences within 16p and the 16p11.2 deletion were associated with decreased average gene expression across 16p. The transcriptional effects of the rare deletion and diffuse common variation were correlated at the level of individual genes and analysis of Hi-C data revealed patterns of chromatin contact that may explain this transcriptional convergence. These results reflect a new approach for extracting biological insight from genetic association data and suggest convergence of common and rare genetic influences on autism at 16p.
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- 2022
41. The phenotypic manifestations of rare CNVs in schizophrenia
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Merikangas, Alison K., Segurado, Ricardo, Cormican, Paul, Heron, Elizabeth A., Anney, Richard J.L., Moore, Susan, Kelleher, Eric, Hargreaves, April, Anderson-Schmidt, Heike, Gill, Michael, Gallagher, Louise, and Corvin, Aiden
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- 2014
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42. Longitudinally stable, brain‐based predictive models mediate the relationships between childhood cognition and socio‐demographic, psychological and genetic factors
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Pat, Narun, primary, Wang, Yue, additional, Anney, Richard, additional, Riglin, Lucy, additional, Thapar, Anita, additional, and Stringaris, Argyris, additional
- Published
- 2022
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43. Investigating direct and indirect genetic effects in attention deficit hyperactivity disorder (ADHD) using parent-offspring trios
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Martin, Joanna, primary, Wray, Matthew, additional, Agha, Sharifah Shameem, additional, Lewis, Katie J. S., additional, Anney, Richard JL, additional, O'Donovan, Michael JL, additional, Thapar, Anita, additional, and Langley, Kate, additional
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- 2022
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44. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder
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Neale, Benjamin M., Medland, Sarah E., Ripke, Stephan, Asherson, Philip, Franke, Barbara, Lesch, Klaus-Peter, Faraone, Stephen V., Nguyen, Thuy Trang, Schafer, Helmut, Holmans, Peter, Daly, Mark, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J., Romanos, Marcel, Romanos, Jasmin, Walitza, Susanne, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Buitelaar, Jan, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Gill, Michael, Anney, Richard J. L., Langely, Kate, O'Donovan, Michael, Williams, Nigel, Owen, Michael, Thapar, Anita, Kent, Lindsey, Sergeant, Joseph, Roeyers, Herbert, Mick, Eric, Biederman, Joseph, Doyle, Alysa, Smalley, Susan, Loo, Sandra, Hakonarson, Hakon, Elia, Josephine, Todorov, Alexandre, Miranda, Ana, Mulas, Fernando, Ebstein, Richard P., Rothenberger, Aribert, Banaschewski, Tobias, Oades, Robert D., Sonuga-Barke, Edmund, McGough, James, Nisenbaum, Laura, Middleton, Frank, Hu, Xiaolan, and Nelson, Stan
- Abstract
Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. Method: We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. Results: No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. Conclusions: Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability. (Contains 3 figures and 3 tables.)
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- 2010
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45. Autism Symptoms in Attention-Deficit/Hyperactivity Disorder: A Familial Trait which Correlates with Conduct, Oppositional Defiant, Language and Motor Disorders
- Author
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Mulligan, Aisling, Anney, Richard J. L, and O'Regan, Myra
- Abstract
It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1 (31%) had few autism symptoms and low comorbidity; Classes 2-4 were intermediate; Class 5 (7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.
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- 2009
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46. DRAGON-Data: A platform and protocol for integrating genomic and phenotypic data across large psychiatric cohorts
- Author
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Hubbard, Leon, primary, Lynham, Amy J., additional, Knott, Sarah, additional, Underwood, Jack F. G., additional, Anney, Richard, additional, Bisson, Jonathan I., additional, van den Bree, Marianne.B.M, additional, Craddock, Nick, additional, O’Donovan, Michael, additional, Jones, Ian, additional, Kirov, George, additional, Langley, Kate, additional, Martin, Joanna, additional, Rice, Frances, additional, Roberts, Neil, additional, Thapar, Anita, additional, Owen, Michael J., additional, Hall, Jeremy, additional, Pardiñas, Antonio F., additional, and Walters, James T.R., additional
- Published
- 2022
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- View/download PDF
47. 27. USING A TRIO-BASED GENETIC DESIGN FOR INVESTIGATING THE AETIOLOGY OF ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD)
- Author
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Martin, Joanna, primary, Wray, Matthew, additional, Agha, Sharifah Shameem, additional, Lewis, Katie, additional, Anney, Richard, additional, O'Donovan, Michael, additional, Thapar, Anita, additional, and Langley, Kate, additional
- Published
- 2021
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48. Towards a gene-level map of resilience to genetic variants associated with autism
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Rolland, Thomas, Cliquet, Freddy, Anney, Richard, Traut, Nicolas, Mathieu, Alexandre, Huguet, Guillaume, Leblond, Claire, Douard, Elise, Amsellem, Frédérique, Malesys, Simon, Maruani, Anna, Toro, Roberto, Packer, Alan, Chung, Wendy, Jacquemont, Sébastien, Delorme, Richard, Bourgeron, Thomas, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Cardiff University, Centre de Recherches Interdisciplinaires (CRI), Université de Paris (UP), Université de Montréal (UdeM), Centre de recherche du CHU Sainte-Justine [Montreal], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Service psychiatrique de l'enfant et de l'adolescent [CHU Hôpital Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Simons Foundation, Columbia University Medical Center (CUMC), Columbia University [New York], This work was funded by Institut Pasteur, the Bettencourt-Schueller Foundation, Université de Paris, the Conny-Maeva Charitable Foundation, the Cognacq Jay Foundation, the Eranet-Neuron (ALTRUISM), the GenMed Labex, AIMS-2-TRIALS which received support from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 and the Inception program (Investissement d’Avenir grant ANR-16-CONV-0005). This project has received funding from the European Union’s Horizon 2020 research and innovative program CANDY under grant agreement No 847818., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Université Paris Cité (UPC)
- Subjects
genetic structures ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,mental disorders ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,behavioral disciplines and activities - Abstract
Posté sur medRxiv le 6 mars 2021.; While over 100 genes are now significantly associated with autism spectrum disorders (ASD), the penetrance of the variants affecting these genes remains poorly understood. Here, we quantified the prevalence of rare loss-of-function (LoF) mutations affecting 156 genes robustly associated with ASD (SPARK genes) using genetic data from more than 10,000 individuals with ASD and 100,000 undiagnosed individuals. We then investigated the clinical, brain imaging and genetic profiles of individuals heterozygous for these rare deleterious variants who were not diagnosed with ASD. These “resilient” individuals, observed in less than 1% of the general population, were equally distributed among males and females, but displayed low polygenic scores for ASD compared to LoF heterozygotes diagnosed with ASD. The interplay between rare and common variants may therefore contribute to the clinical profiles of the individuals carrying LoF in genes associated with ASD.
- Published
- 2021
49. Common variants in genes of the postsynaptic FMRP signalling pathway are risk factors for autism spectrum disorders
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Waltes, Regina, Duketis, Eftichia, Knapp, Michael, Anney, Richard J. L., Huguet, Guillaume, Schlitt, Sabine, Jarczok, Tomasz A., Sachse, Michael, Kämpfer, Laura M., Kleinböck, Tina, Poustka, Fritz, Bölte, Sven, Schmötzer, Gabriele, Voran, Anette, Huy, Ellen, Meyer, Jobst, Bourgeron, Thomas, Klauck, Sabine M., Freitag, Christine M., and Chiocchetti, Andreas G.
- Published
- 2014
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50. Detecting Allelic Expression Imbalance at Candidate Genes Using 5′ Exonuclease Genotyping Technology
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Gahan, Jillian M., primary, Byrne, Mikaela M., additional, Hill, Matthew, additional, Quinn, Emma M., additional, Murphy, Ross T., additional, Anney, Richard J. L., additional, and Ryan, Anthony W., additional
- Published
- 2015
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