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Oct 2, 2024 | 
biorxiv.org | Wenhan Lu |Siwei Chen |Danielle Posthuma |Benjamin M. Neale
AbstractGenome-wide association studies (GWAS) and rare-variant association studies (RVAS) have identified thousands of genes and variants that affect multiple phenotypes. Here, using rare variant association results from the UK Biobank (UKB) data, we identify pervasive gene-level pleiotropy across diverse phenotypic domains and highlight genes with apparent allelic series that provide additional association support through disease pathways.
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Sep 28, 2024 | 
medrxiv.org | Douglas P. Wightman |Bernardo Maciel |Rachel M. Brouwer |Danielle Posthuma
The authors have declared no competing interest. DP was funded by The Netherlands Organization for Scientific Research (NWO VICI 453-14-005), NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012), and a European Research Council advanced grant (Grant No, ERC-2018-AdG GWAS2FUNC 834057). DW was funded by NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012).
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Sep 24, 2024 | 
medrxiv.org | Jeanne E. Savage |Danielle Dick |Danielle Posthuma |Vrije Universiteit Amsterdam
The authors have declared no competing interest. This research was funded by a grant to J.E.S. (VI.VENI.201G-064) from The Netherlands Organization for Scientific Research (NWO).
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Aug 30, 2024 | 
biorxiv.org | Tom Bresser |Jeanne E. Savage |Danielle Posthuma |Elleke Tissink
AbstractInsomnia disorder, major depressive disorder and anxiety disorders are the most common mental health conditions, with high comorbidity and genetic overlap suggesting shared brain mechanisms. Studies on brain correlates of these disorders have not fully addressed this overlap.
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Jul 29, 2024 | 
medrxiv.org | Marijn Schipper |Jacob C. Ulirsch |Danielle Posthuma |Karl Heilbron
M.S., D.P., and S.R. have nothing to disclose. J.C.U. is an employee of Illumina. K.H. is a former employee of 23andMe, Inc. and owns 23andMe, Inc. stock options. SR discloses support for the research of this work from the German Center for Mental Health (DZPG), the European Union's Horizon program (101057454, "PsychSTRATA"), and The German Research Foundation (402170461, grant "TRR265").
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Jun 3, 2024 | 
nature.com | Oleksandr Frei |Guy Hindley |Espen Hagen |Nadine Staples Parker |Olav B. Smeland |Christiaan de Leeuw | +2 more
AbstractWhile genome-wide association studies are increasingly successful in discovering genomic loci associated with complex human traits and disorders, the biological interpretation of these findings remains challenging.
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May 1, 2024 | 
nature.com | Lijuan Hu |Marijn Schipper |Caleb C. Reagor |Xiaofei Li |Xiaoling He |Roger Barker | +2 more
AbstractThe human brain develops through a tightly organized cascade of patterning events, induced by transcription factor expression and changes in chromatin accessibility. Although gene expression across the developing brain has been described at single-cell resolution1, similar atlases of chromatin accessibility have been primarily focused on the forebrain2,3,4.
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Mar 15, 2024 | 
medrxiv.org | Jeanne E. Savage |Josefin Werme |Danielle Dick |Danielle Posthuma
The authors have declared no competing interest. This research was funded by a grant to J.E.S. (VI.VENI.201G-064) from The Netherlands Organization for Scientific Research (NWO) and has been conducted using the UK Biobank Resource (application no. 16406). Analyses were carried out on the Genetic Cluster Computer hosted by the Dutch National computing and Networking Services SURFsara.
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Jul 24, 2023 | 
nature.com | Danielle Dick |Danielle Posthuma |Anaïs B. Thijssen
SampleParticipants were volunteers of the UK Biobank (UKB), a population-based sample of ~500,000 adults in the UK aged 40–65 [18]. After providing informed consent, participants completed a self-report survey, and a subset (n = 157,366) later completed an online mental health questionnaire. Medical records of participants were linked via national health registries, and additional diagnoses were obtained through interviews and the online survey (self-reports of clinically diagnosed conditions).
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May 22, 2023 | 
nature.com | Danielle Posthuma
AbstractGenome-wide association studies have led to the identification of robust statistical associations of genetic variants with numerous brain-related traits, including neurological and psychiatric conditions, and psychological and behavioral measures. These results may provide insight into the biology underlying these traits and may facilitate clinically useful predictions.
