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

Project Information

GWAS2FUNC

Grant agreement ID: 834057

DOI

10.3030/834057

Project closed

EC signature date 25 July 2019

Start date 1 September 2019

End date 31 August 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 378 412,00

EU contribution

€ 2 378 412,00

Coordinated by

STICHTING VU
Netherlands

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

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.

Publications

Peer reviewed articles (27)

An integrated framework for local genetic correlation analysis

Author(s): Josefin Werme, Sophie van der Sluis, Danielle Posthuma, Christiaan A. de Leeuw
Published in: Nature Genetics, Issue March 14, 2022, 2022, ISSN 1061-4036
Publisher: 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

Author(s): Yongbin Wei, Siemon C. de Lange, Rory Pijnenburg, Lianne H. Scholtens, Dirk Jan Ardesch, Kyoko Watanabe, Danielle Posthuma, Martijn P. van den Heuvel
Published in: Human Brain Mapping, Issue Feb 15 2022, 2021, Page(s) 885-901, ISSN 1097-0193
Publisher: 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

Author(s): 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
Published in: Communications Biology, Issue 5(710), 2022, ISSN 2399-3642
Publisher: Springer Nature
DOI: 10.1038/s42003-022-03672-7

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

Author(s): 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
Published in: Nature Communications, Issue 15, 2024, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-024-46817-4

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

Author(s): 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
Published in: Acta Neuropathologica, Issue Volume 144, 2022, Page(s) 821-842, ISSN 0001-6322
Publisher: Springer Verlag
DOI: 10.1007/s00401-022-02454-z

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

Author(s): 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
Published in: eNeuro, Issue 10(4), 2023, ISSN 2373-2822
Publisher: 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

Author(s): 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
Published in: Neurobiology of Disease, Issue 183, 2024, Page(s) 106174, ISSN 0969-9961
Publisher: Academic Press
DOI: 10.1016/j.nbd.2023.106174

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

Author(s): 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
Published in: Nature Communications, Issue 11, 2022, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-19378-5

Local genetic sex differences in quantitative traits

Author(s): Emil Uffelmann, Christiaan de Leeuw, Marijn Schipper, Danielle Posthuma
Published in: Nature Communications, Issue 16, 2025, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-025-62504-4

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

Author(s): 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
Published in: NPJ Parkinson's Disease, 2025, ISSN 2373-8057
Publisher: 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

Author(s): Emil Uffelmann, Danielle Posthuma, Wouter J. Peyrot
Published in: Scientific Reports - Nature, Issue 4219 (2023), 2023, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-023-29428-9

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

Author(s): 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
Published in: Nature Genetics, Issue 54(8), 2022, Page(s) 1125-1132, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-022-01124-w

Estimating disorder probability based on polygenic prediction using the BPC approach

Author(s): 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
Published in: Nature Communications, Issue 16, 2025, ISSN 2041-1723
Publisher: 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

Author(s): Douglas P. Wightman, Jeanne E. Savage, Elleke Tissink, Cato Romero, Iris E. Jansen, Danielle Posthuma
Published in: Neurobiology of Aging, Issue Volume 127, 2023, Page(s) 99-112, ISSN 0197-4580
Publisher: Elsevier BV
DOI: 10.1016/j.neurobiolaging.2023.03.004

Emerging Methods and Resources for Biological Interrogation of Neuropsychiatric Polygenic Signal

Author(s): Emil Uffelmann, Danielle Posthuma
Published in: Biological Psychiatry, Issue 89/1, 2021, Page(s) 41-53, ISSN 0006-3223
Publisher: Elsevier BV
DOI: 10.1016/j.biopsych.2020.05.022

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

Author(s): Josefin Werme, Sophie van der Sluis, Danielle Posthuma & Christiaan A. de Leeuw
Published in: Translational Psychiatry, Issue March 22, 2021, 2021, Page(s) Article number: 180, ISSN 2158-3188
Publisher: 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

Author(s): 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
Published in: Nature Genetics, Issue September 7, 2021, 2021, Page(s) 1276–1282, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-021-00977-x

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

Author(s): 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
Published in: Nature Genetics, Issue 57, 2025, Page(s) 1389-1401, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-025-02189-z

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

Author(s): 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
Published in: Molecular Psychiatry, Issue 28, 2024, Page(s) 4225-4233, ISSN 1359-4184
Publisher: Nature Publishing Group
DOI: 10.1038/s41380-023-02174-0

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

Author(s): Ilan Libedinsky, Yongbin Wei, Christiaan de Leeuw, James K Rilling, Danielle Posthuma, Martijn P van den Heuvel
Published in: Cerebral Cortex, Issue 35, 2025, ISSN 1047-3211
Publisher: Oxford University Press
DOI: 10.1093/cercor/bhaf127

Exploring the genetic overlap between twelve psychiatric disorders

Author(s): 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
Published in: Nature Genetics, Issue 54, 2022, Page(s) 1795-1802, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-022-01245-2

On the interpretation of transcriptome-wide association studies

Author(s): Christiaan de Leeuw, Josefin Werme, Jeanne E. Savage, Wouter J. Peyrot, Danielle Posthuma
Published in: PLOS Genetics, Issue 19(9): e101092, 2023, ISSN 1553-7390
Publisher: Public Library of Science
DOI: 10.1371/journal.pgen.1010921

Genome-wide association studies

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

Prioritizing effector genes at trait-associated loci using multimodal evidence

Author(s): 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
Published in: Nature Genetics, Issue 57, 2025, Page(s) 323-333, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-025-02084-7

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

Author(s): Douglas P. Wightman, Jeanne E. Savage, Christiaan A. de Leeuw, Iris E. Jansen, Danielle Posthuma
Published in: Scientific Reports, Issue 13, 2023, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-023-29108-8

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

Author(s): Marijn Schipper, Danielle Posthuma
Published in: Human Molecular Genetics, Issue Volume 31, Issue R1, 2022, Page(s) R73-R83, ISSN 0964-6906
Publisher: 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

Author(s): Matthieu C. de Hemptinne, Danielle Posthuma
Published in: Nature Neuroscience, Issue 26, 2023, Page(s) 932-941, ISSN 1097-6256
Publisher: Nature Publishing Group
DOI: 10.1038/s41593-023-01333-4

Other (15)

Mapping the genetic evolutionary timeline of human neural and cognitive traits

Author(s): Ilan Libedinsky; Yongbin Wei; Christiaan de Leeuw; James K. Rilling; Danielle Posthuma; Martijn P. van den Heuvel
Published in: bioRxiv, Issue Sep 28, 2023, 2023
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.02.05.525539

Genome-wide association study of cerebellar volume

Author(s): 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
Published in: bioRxiv, Issue November 4, 2021, 2021
Publisher: 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

Author(s): Stephanie Beekhuis-Hoekstra; Karen Laupman; Yongbin Wei; Kyoko Watanabe; Paulien Cornelissen-Steijger; Patrick Sullivan; Danielle Posthuma; Vivi Heine
Published in: Research Square, Issue 15 JUl, 2022, 2022, ISSN 2693-5015
Publisher: Research Square
DOI: 10.21203/rs.3.rs-1811182/v1

Reconsidering the validity of transcriptome-wide association studies

Author(s): Christiaan de Leeuw, Josefin Werme, Jeanne Savage, Wouter Peyrot, Danielle Posthuma
Published in: BioRxiv, Issue August 15, 2021, 2021
Publisher: BioRxiv
DOI: 10.1101/2021.08.15.456414

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

Author(s): 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
Published in: medRxiv, 2022
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2020.11.20.20235275

Estimating Disorder Probability Based on Polygenic Prediction Using the BPC Approach

Author(s): 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
Published in: medRxiv, Issue January 14, 2024, 2024
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.01.12.24301157

The genetic landscape of heterogeneity in human functional brain connectivity

Author(s): Bernardo de APC Maciel, Marijn Schipper, Cato Romero, Christiaan de Leeuw, Koen Helwegen, Danielle Posthuma, Jeanne E. Savage, Martijn P. van den Heuvel
Published in: medRxiv, 2025
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2025.04.08.25325384

Genomic analyses reveal new insights into Alzheimer’s disease

Author(s): 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
Published in: medRxiv, 2025, ISSN 3067-2007
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2025.10.10.25337470

Local Genetic Sex Differences in Quantitative Traits

Author(s): Emil Uffelmann, Christiaan de Leeuw, Danielle Posthuma
Published in: medRxiv, Issue May 4, 2023, 2023
Publisher: 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

Author(s): Douglas P Wightman, Jeanne E Savage, Christiaan A de Leeuw, Iris E Jansen, Danielle Posthuma
Published in: medRxiv, Issue October 18, 2021, 2021
Publisher: medRxiv
DOI: 10.1101/2021.10.17.21265070

Re-Evaluating Local Genetic Correlation Analysis in the HDL Framework

Author(s): Christiaan de Leeuw, Josefin Werme, Danielle Posthuma
Published in: Preprints.org, 2025
Publisher: MDPI AG
DOI: 10.20944/preprints202507.0966.v1

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

Author(s): 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
Published in: medRxiv, Issue December 7, 2020, 2020
Publisher: bioRxiv
DOI: 10.1101/2020.12.07.20245209

Simplifying causal gene identification in GWAS loci

Author(s): Marijn Schipper, Jacob Ulirsch, Danielle Posthuma, Stephan Ripke, Karl Heilbron
Published in: medRxiv, 2025
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.07.26.24311057

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

Author(s): 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
Published in: bioRxiv, Issue 20 December, 2022, 2022
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2022.12.20.521181

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

Author(s): J. Werme; E.P. Tissink; S.C. de Lange; M.P. van den Heuvel; D. Posthuma; C.A. de Leeuw
Published in: medRxiv, Issue March 3, 2023, 2023
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.03.01.23286613

Conference proceedings (1)

Identifying drug targets for schizophrenia through gene prioritization

Author(s): Julia Kraft, Alice Braun, Swapnil Awasthi, Georgia Panagiotaropoulou, Marijn Schipper, Nathaniel Bell, Danielle Posthuma, Antonio F. Pardiñas, null null, Stephan Ripke, Karl Heilbron
Published in: medRxiv, 2024
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.05.15.24307423