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

Deliverables

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

Publications

An integrated framework for local genetic correlation analysis

Author(s): Josefin Werme, Sophie van der Sluis, Danielle Posthuma, Christiaan 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

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

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 November 5, 2020, 2020, Page(s) Article Number: 5606, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-19378-5

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

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

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

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

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

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

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

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

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

Deliverables

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