From GWAS to functional studies: Tackling the complex nature of brain disorders

Información del proyecto

GWAS2FUNC

Identificador del acuerdo de subvención: 834057

DOI

10.3030/834057

Proyecto cerrado

Fecha de la firma de la CE 25 Julio 2019

Fecha de inicio 1 Septiembre 2019

Fecha de finalización 31 Agosto 2025

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 2 378 412,00

Aportación de la UE

€ 2 378 412,00

Coordinado por

STICHTING VU
Netherlands

CORDIS proporciona enlaces a los documentos públicos y las publicaciones de los proyectos de los programas marco HORIZONTE.

Los enlaces a los documentos y las publicaciones de los proyectos del Séptimo Programa Marco, así como los enlaces a algunos tipos de resultados específicos, como conjuntos de datos y «software», se obtienen dinámicamente de OpenAIRE .

Resultado final

Open Research Data Pilot (1)

Data Management Plan

After 6 months the initial data management plan will be delivered and updated during the lifespan of the project.

Publicaciones

Peer reviewed articles (26)

An integrated framework for local genetic correlation analysis

Autores: Josefin Werme, Sophie van der Sluis, Danielle Posthuma, Christiaan de Leeuw
Publicado en: Nature Genetics, Edición March 14, 2022, 2022, ISSN 1061-4036
Editor: Nature Publishing Group
DOI: 10.1101/2020.12.31.424652

Statistical testing in transcriptomic-neuroimaging studies: A how-to and evaluation of methods assessing spatial and gene specificity

Autores: Yongbin Wei, Siemon C. de Lange, Rory Pijnenburg, Lianne H. Scholtens, Dirk Jan Ardesch, Kyoko Watanabe, Danielle Posthuma, Martijn P. van den Heuvel
Publicado en: Human Brain Mapping, Edición Feb 15 2022, 2021, Página(s) 885-901, ISSN 1097-0193
Editor: Wiley Online Library
DOI: 10.1002/hbm.25711

Genome-wide association study of cerebellar volume provides insights into heritable mechanisms underlying brain development and mental health

Autores: Elleke Tissink; Siemon C. de Lange; Jeanne E. Savage; Douglas P. Wightman; Christiaan A. de Leeuw; Kristen M. Kelly; Mats Nagel; Martijn P. van den Heuvel; Danielle Posthuma
Publicado en: Communications Biology, Edición 5(710), 2022, ISSN 2399-3642
Editor: Springer Nature
DOI: 10.1038/s42003-022-03672-7

Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers

Autores: Jansen, Iris; van der Lee, Sven J; Bellenguez, Céline; Ramakers, Inez; Rodriguez-Rodriguez, Eloy; Rujescu, Dan; Saltvedt, Ingvild; Sanchez-Juan, Pascual; Scheltens, Philip; Scherbaum, Norbert; Schmid, Matthias; Schneider, Anja; Selbæk, Geir; Kleineidam, Luca; Selnes, Per; Shadrin, Alexey; Skoog, Ingmar; Soininen, Hilkka; Tárraga, Lluís; Teipel, Stefan; group, GR@ACE study; Tijms, Betty; Tsolak
Publicado en: Acta Neuropathologica, Edición Volume 144, 2022, Página(s) 821-842, ISSN 0001-6322
Editor: Springer Verlag
DOI: 10.1007/s00401-022-02454-z

The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

Autores: Elleke Tissink; Josefin Werme; Siemon C. de Lange; Jeanne E. Savage; Yongbin Wei; Christiaan A. de Leeuw; Mats Nagel; Danielle Posthuma; Martijn P. van den Heuvel
Publicado en: eNeuro, Edición 10(4), 2023, ISSN 2373-2822
Editor: Society for Neuroscience
DOI: 10.1523/eneuro.0242-22.2023

Shared genetic loci between Alzheimer's disease and multiple sclerosis: Crossroads between neurodegeneration and immune system

Autores: Vera Fominykh, Alexey A. Shadrin, Piotr P. Jaholkowski, Shahram Bahrami, Lavinia Athanasiu, Douglas P. Wightman, Emil Uffelmann, Danielle Posthuma, Geir Selbæk, Anders M. Dale, Srdjan Djurovic, Oleksandr Frei, Ole A. Andreassen
Publicado en: Neurobiology of Disease, Edición 183, 2024, Página(s) 106174, ISSN 0969-9961
Editor: Academic Press
DOI: 10.1016/j.nbd.2023.106174

Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence

Autores: Philip R. Jansen, Mats Nagel, Kyoko Watanabe, Yongbin Wei, Jeanne E. Savage, Christiaan A. de Leeuw, Martijn P. van den Heuvel, Sophie van der Sluis & Danielle Posthuma
Publicado en: Nature Communications, Edición November 5, 2020, 2020, Página(s) Article Number: 5606, ISSN 2041-1723
Editor: Nature Publishing Group
DOI: 10.1038/s41467-020-19378-5

Local genetic sex differences in quantitative traits

Autores: Emil Uffelmann, Christiaan de Leeuw, Marijn Schipper, Danielle Posthuma
Publicado en: Nature Communications, Edición 16, 2025, ISSN 2041-1723
Editor: Nature Publishing Group
DOI: 10.1038/s41467-025-62504-4

Prioritizing Parkinson’s disease risk genes in genome-wide association loci

Autores: Lara M. Lange, Catalina Cerquera-Cleves, Marijn Schipper, Georgia Panagiotaropoulou, Alice Braun, Julia Kraft, Swapnil Awasthi, Nathaniel Bell, Danielle Posthuma, Stephan Ripke, Cornelis Blauwendraat, Karl Heilbron
Publicado en: NPJ Parkinson's Disease, 2025, ISSN 2373-8057
Editor: Springer Nature
DOI: 10.1101/2024.12.13.24318996

Genome-wide association studies of polygenic risk score-derived phenotypes may lead to inflated false positive rates

Autores: Emil Uffelmann, Danielle Posthuma, Wouter J. Peyrot
Publicado en: Scientific Reports - Nature, Edición 4219 (2023), 2023, ISSN 2045-2322
Editor: Nature Publishing Group
DOI: 10.1038/s41598-023-29428-9

Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways

Autores: Kyoko Watanabe; Philip R. Jansen; Jeanne E. Savage; Priyanka Nandakumar; Xin Wang; Michelle Agee; Stella Aslibekyan; Adam Auton; Robert K. Bell; Katarzyna Bryc; Sarah K. Clark; Sarah L. Elson; Kipper Fletez-Brant; Pierre Fontanillas; Nicholas A. Furlotte; Pooja M. Gandhi; Karl Heilbron; Barry Hicks; Karen E. Huber; Ethan M. Jewett; Yunxuan Jiang; Aaron Kleinman; Keng-Han Lin; Nadia K. Litterman; J
Publicado en: Nature Genetics, Edición 54(8), 2022, Página(s) 1125-1132, ISSN 1061-4036
Editor: Nature Publishing Group
DOI: 10.1038/s41588-022-01124-w

Estimating disorder probability based on polygenic prediction using the BPC approach

Autores: Emil Uffelmann, null null, Cathryn M. Lewis, Andrew M. McIntosh, null null, Micheal C. O’Donovan, James T. R. Walters, Alkes L. Price, Danielle Posthuma, Wouter J. Peyrot
Publicado en: Nature Communications, Edición 16, 2025, ISSN 2041-1723
Editor: Nature Publishing Group
DOI: 10.1038/s41467-025-62929-x

The genetic overlap between Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease

Autores: Douglas P. Wightman, Jeanne E. Savage, Elleke Tissink, Cato Romero, Iris E. Jansen, Danielle Posthuma
Publicado en: Neurobiology of Aging, Edición Volume 127, 2023, Página(s) 99-112, ISSN 0197-4580
Editor: Elsevier BV
DOI: 10.1016/j.neurobiolaging.2023.03.004

Emerging Methods and Resources for Biological Interrogation of Neuropsychiatric Polygenic Signal

Autores: Emil Uffelmann, Danielle Posthuma
Publicado en: Biological Psychiatry, Edición 89/1, 2021, Página(s) 41-53, ISSN 0006-3223
Editor: Elsevier BV
DOI: 10.1016/j.biopsych.2020.05.022

Genome-wide gene-environment interactions in neuroticism: an exploratory study across 25 environments

Autores: Josefin Werme, Sophie van der Sluis, Danielle Posthuma & Christiaan A. de Leeuw
Publicado en: Translational Psychiatry, Edición March 22, 2021, 2021, Página(s) Article number: 180, ISSN 2158-3188
Editor: Nature Publishing Group
DOI: 10.1038/s41398-021-01334-6

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease

Autores: Douglas P. Wightman, Iris E. Jansen, Jeanne E. Savage, Alexey A. Shadrin, Shahram Bahrami, Dominic Holland, Arvid Rongve, Sigrid Børte, Bendik S. Winsvold, Ole Kristian Drange, Amy E. Martinsen, Anne Heidi Skogholt, Cristen Willer, Geir Bråthen, Ingunn Bosnes, Jonas Bille Nielsen, Lars G. Fritsche, Laurent F. Thomas, Linda M. Pedersen, Maiken E. Gabrielsen, Marianne Bakke Johnsen, Tore Wergeland
Publicado en: Nature Genetics, Edición September 7, 2021, 2021, Página(s) 1276–1282, ISSN 1061-4036
Editor: Nature Publishing Group
DOI: 10.1038/s41588-021-00977-x

Genome-wide analyses identify 30 loci associated with obsessive–compulsive disorder

Autores: Nora I. Strom, Zachary F. Gerring, Marco Galimberti, Dongmei Yu, Matthew W. Halvorsen, Abdel Abdellaoui, Cristina Rodriguez-Fontenla, Julia M. Sealock, Tim Bigdeli, Jonathan R. Coleman, Behrang Mahjani, Jackson G. Thorp, Katharina Bey, Christie L. Burton, Jurjen J. Luykx, Gwyneth Zai, Silvia Alemany, Christine Andre, Kathleen D. Askland, Julia Bäckman, Nerisa Banaj, Cristina Barlassina, Judith Be
Publicado en: Nature Genetics, Edición 57, 2025, Página(s) 1389-1401, ISSN 1061-4036
Editor: Nature Publishing Group
DOI: 10.1038/s41588-025-02189-z

Investigating genetically stratified subgroups to better understand the etiology of alcohol misuse

Autores: Anaïs B. Thijssen, null null, null null, Karen Chartier, null null, Ananda Amstadter, null null, Danielle M. Dick, null null, Emily Lilley, Renolda Gelzinis, Anne Morris, null null, Katie Bountress, Amy E. Adkins, Nathaniel Thomas, Zoe Neale, Kimberly Pedersen, Thomas Bannard, Seung B. Cho, null null, Peter Barr, Holly Byers, Erin C. Berenz, Erin Caraway, James S. Clifford, Megan Cooke, Elizabeth
Publicado en: Molecular Psychiatry, Edición 28, 2024, Página(s) 4225-4233, ISSN 1359-4184
Editor: Nature Publishing Group
DOI: 10.1038/s41380-023-02174-0

The emergence of genetic variants linked to brain and cognitive traits in human evolution

Autores: Ilan Libedinsky, Yongbin Wei, Christiaan de Leeuw, James K Rilling, Danielle Posthuma, Martijn P van den Heuvel
Publicado en: Cerebral Cortex, Edición 35, 2025, ISSN 1047-3211
Editor: Oxford University Press
DOI: 10.1093/cercor/bhaf127

Exploring the genetic overlap between twelve psychiatric disorders

Autores: ato Romero, Josefin Werme, Philip R. Jansen, Joel Gelernter, Murray B. Stein, Daniel Levey, Renato Polimanti, Christiaan de Leeuw, Danielle Posthuma, Mats Nagel, Sophie van der Sluis
Publicado en: Nature Genetics, Edición 54, 2022, Página(s) 1795-1802, ISSN 1061-4036
Editor: Nature Publishing Group
DOI: 10.1038/s41588-022-01245-2

On the interpretation of transcriptome-wide association studies

Autores: Christiaan de Leeuw, Josefin Werme, Jeanne E. Savage, Wouter J. Peyrot, Danielle Posthuma
Publicado en: PLOS Genetics, Edición 19(9): e101092, 2023, ISSN 1553-7390
Editor: Public Library of Science
DOI: 10.1371/journal.pgen.1010921

Genome-wide association studies

Autores: Emil Uffelmann, Qin Qin Huang, Nchangwi Syntia Munung, Jantina de Vries, Yukinori Okada, Alicia R. Martin, Hilary C. Martin, Tuuli Lappalainen & Danielle Posthuma
Publicado en: Nature Reviews Methods Primers, Edición August 29, 2021, 2021, Página(s) Article number: 59, ISSN 2662-8449
Editor: Nature portfolio
DOI: 10.1038/s43586-021-00056-9

Prioritizing effector genes at trait-associated loci using multimodal evidence

Autores: Marijn Schipper, Christiaan A. de Leeuw, Bernardo A. P. C. Maciel, Douglas P. Wightman, Nikki Hubers, Dorret I. Boomsma, Michael C. O’Donovan, Danielle Posthuma
Publicado en: Nature Genetics, Edición 57, 2025, Página(s) 323-333, ISSN 1061-4036
Editor: Nature Publishing Group
DOI: 10.1038/s41588-025-02084-7

Rare variant aggregation in 148,508 exomes identifies genes associated with proxy dementia

Autores: Douglas P. Wightman, Jeanne E. Savage, Christiaan A. de Leeuw, Iris E. Jansen, Danielle Posthuma
Publicado en: Scientific Reports, Edición 13, 2023, ISSN 2045-2322
Editor: Nature Publishing Group
DOI: 10.1038/s41598-023-29108-8

Demystifying non-coding GWAS variants: an overview of computational tools and methods

Autores: Marijn Schipper, Danielle Posthuma
Publicado en: Human Molecular Genetics, Edición Volume 31, Edición R1, 2022, Página(s) R73-R83, ISSN 0964-6906
Editor: Oxford University Press
DOI: 10.1093/hmg/ddac198

Addressing the ethical and societal challenges posed by genome-wide association studies of behavioral and brain-related traits

Autores: Matthieu C. de Hemptinne, Danielle Posthuma
Publicado en: Nature Neuroscience, Edición 26, 2023, Página(s) 932-941, ISSN 1097-6256
Editor: Nature Publishing Group
DOI: 10.1038/s41593-023-01333-4

Other (13)

Mapping the genetic evolutionary timeline of human neural and cognitive traits

Autores: Ilan Libedinsky; Yongbin Wei; Christiaan de Leeuw; James K. Rilling; Danielle Posthuma; Martijn P. van den Heuvel
Publicado en: bioRxiv, Edición Sep 28, 2023, 2023
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.02.05.525539

Genome-wide association study of cerebellar volume

Autores: E.P. Tissink, S.C. de Lange, J.E. Savage, D.P. Wightman, K.M. Kelly, M. Nagel, M.P. van den Heuvel, D. Posthuma
Publicado en: bioRxiv, Edición November 4, 2021, 2021
Editor: bioRxiv
DOI: 10.1101/2021.11.04.467250

Patient iPSC-derived astrocytes with high polygenic risk for schizophrenia reveals a role for mitochondrial glutamate carrier SLC25A18

Autores: Stephanie Beekhuis-Hoekstra; Karen Laupman; Yongbin Wei; Kyoko Watanabe; Paulien Cornelissen-Steijger; Patrick Sullivan; Danielle Posthuma; Vivi Heine
Publicado en: Research Square, Edición 15 JUl, 2022, 2022, ISSN 2693-5015
Editor: Research Square
DOI: 10.21203/rs.3.rs-1811182/v1

Reconsidering the validity of transcriptome-wide association studies

Autores: Christiaan de Leeuw, Josefin Werme, Jeanne Savage, Wouter Peyrot, Danielle Posthuma
Publicado en: BioRxiv, Edición August 15, 2021, 2021
Editor: BioRxiv
DOI: 10.1101/2021.08.15.456414

Largest GWAS (N=1,126,563) of Alzheimer’s Disease Implicates Microglia and Immune Cells

Autores: Douglas P Wightman, Iris E Jansen, Jeanne E. Savage, Alexey A Shadrin, Shahram Bahrami, Arvid Rongve, Sigrid Børte, Bendik S Winsvold, Ole Kristian Drange, Amy E Martinsen, Anne Heidi Skogholt, Cristen Willer, Geir Bråthen, Ingunn Bosnes, Jonas Bille Nielsen, Lars Fritsche, Laurent F. Thomas, Linda M Pedersen, Maiken E Gabrielsen, Marianne Bakke Johnsen, Tore Wergeland Meisingset, Wei Zhou, Petr
Publicado en: medRxiv, 2022
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2020.11.20.20235275

Estimating Disorder Probability Based on Polygenic Prediction Using the BPC Approach

Autores: Emil Uffelmann, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Alkes L. Price, Danielle Posthuma, Wouter J. Peyrot
Publicado en: medRxiv, Edición January 14, 2024, 2024
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.01.12.24301157

The genetic landscape of heterogeneity in human functional brain connectivity

Autores: Bernardo de APC Maciel, Marijn Schipper, Cato Romero, Christiaan de Leeuw, Koen Helwegen, Danielle Posthuma, Jeanne E. Savage, Martijn P. van den Heuvel
Publicado en: medRxiv, 2025
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2025.04.08.25325384

Local Genetic Sex Differences in Quantitative Traits

Autores: Emil Uffelmann, Christiaan de Leeuw, Danielle Posthuma
Publicado en: medRxiv, Edición May 4, 2023, 2023
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.05.04.539410

Rare Variant Aggregation in 148,508 Exomes Identifies Genes Associated with Proxy Alzheimer’s Disease

Autores: Douglas P Wightman, Jeanne E Savage, Christiaan A de Leeuw, Iris E Jansen, Danielle Posthuma
Publicado en: medRxiv, Edición October 18, 2021, 2021
Editor: medRxiv
DOI: 10.1101/2021.10.17.21265070

Genome-wide meta-analysis of insomnia in over 2.3 million individuals implicates involvement of specific biological pathways through gene-prioritization

Autores: Kyoko Watanabe, Philip R. Jansen, Jeanne E. Savage, Priyanka Nandakumar, Xin Wang, 23andMe Research Team, David A. Hinds, Joel Gelernter, Daniel F. Levey, Renato Polimanti, Murray B. Stein, Eus J.W. Van Someren, August B. Smit, Danielle Posthuma
Publicado en: medRxiv, Edición December 7, 2020, 2020
Editor: bioRxiv
DOI: 10.1101/2020.12.07.20245209

Simplifying causal gene identification in GWAS loci

Autores: Marijn Schipper, Jacob Ulirsch, Danielle Posthuma, Stephan Ripke, Karl Heilbron
Publicado en: medRxiv, 2025
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.07.26.24311057

Abundant pleiotropy across neuroimaging modalities identified through a multivariate genome-wide association study

Autores: E.P. Tissink; A.A. Shadrin; D. van der Meer; N. Parker; G. Hindley; D. Roelfs; O. Frei; C.C. Fan; M. Nagel; T. Nærland; M. Budisteanu; S. Djurovic; L. T. Westlye; M.P. van den Heuvel; D. Posthuma; T. Kaufmann; A.M. Dale; O.A. Andreassen
Publicado en: bioRxiv, Edición 20 December, 2022, 2022
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2022.12.20.521181

Local genetic correlation analysis links depression with molecular and brain imaging endophenotypes

Autores: J. Werme; E.P. Tissink; S.C. de Lange; M.P. van den Heuvel; D. Posthuma; C.A. de Leeuw
Publicado en: medRxiv, Edición March 3, 2023, 2023
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.03.01.23286613

Conference proceedings (1)

Identifying drug targets for schizophrenia through gene prioritization

Autores: Julia Kraft, Alice Braun, Swapnil Awasthi, Georgia Panagiotaropoulou, Marijn Schipper, Nathaniel Bell, Danielle Posthuma, Antonio F. Pardiñas, null null, Stephan Ripke, Karl Heilbron
Publicado en: medRxiv, 2024
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.05.15.24307423

Non-peer reviewed articles (1)

Genomic analyses reveal new insights into Alzheimer’s disease

Autores: Emil Uffelmann, Douglas P. Wightman, Shahram Bahrami, Alexey A. Shadrin, Vera Fominykh, Takafumi Ojima, Chenyang Jiang, Christian Benner, Elisa Moreno, Adrian I. Campos, Jesper Q. Thomassen, Emmanuel Minois-Genin, Hei Man Wu, G. Bragi Walters, Richard Sherva, Tian Lin, Julien Bryois, Kristi Krebs, Marijn Schipper, Akira Narita, Alessandro Serretti, Anja H. Simonsen, Anna L. van Seumeren, Anne Corb
Publicado en: medRxiv, 2025, ISSN 3067-2007
Editor: Cold Spring Harbor Laboratory
DOI: 10.1101/2025.10.10.25337470