Is this you? As a journalist, you can create a free Muck Rack account to customize your profile, list your contact preferences, and upload a portfolio of your best work.
Claim your profile
Articles by Danielle Posthuma
Age-dependent genetic effects on body mass index in the UK Biobank: a SNP-level approach
Abstract Human traits frequently change with age, but this variability is often overlooked in traditional genome-wide association studies (GWASs). One such trait, for which genetic and environmental influences change with age, is BMI. Using a SNP-by-age interaction (GxA) GWAS (fastGWA-GE), we estimated age-varying genetic effects on BMI in the UK Biobank (N unrelated = 380,138; N unrelated + related = 451,696).
Distinguishing different psychiatric disorders using DDx-PRS
|
Abstract Despite great progress on case–control polygenic prediction, an unmet need remains for a method that genetically distinguishes clinically related disorders (e.g., schizophrenia (SCZ) versus bipolar disorder (BIP) versus major depressive disorder (MDD) versus controls).
By Wouter J. Peyrot, Georgia Panagiotaropoulou, Loes M. Olde Loohuis, Mark Adams, Ole A. Andreassen, Swapnil Awasthi, Andreas J. Forstner, Tian Ge, ANDREW McIntosh, Andrew Mcintosh, Brittany Mitchell Verified, Niamh Mullins, Kevin O’Connell, Brenda W.J.H. Penninx, Danielle Posthuma, Stephan Ripke, Douglas M Ruderfer, Emil Uffelmann, Bjarni J Vilhjálmsson, Zhihong Zhu, Jordan W. Smoller, Alkes L Price
|
Nature
Verified
Rare-variant aggregation highlights disease-linked genes associated with brain volume variation
Keywords rare variant exome wide association study brain volume PTEN DISP1 SCUBE2 FA2H neurological disease cerebellum white matter Get full text access Log in, subscribe or purchase for full access. References 1. Boedhoe, P.S.W. ∙ van Rooij, D. ∙ Hoogman, M. ... Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups Am. J. Psychiatry. 2020; 177:834-843 2. van Erp, T.G.M. ∙ Walton, E. ∙ Hibar, D.P. ...
Re-Evaluating Local Genetic Correlation Analysis in the HDL Framework
Choose an area of interest and we will send you notifications of new preprints at your preferred frequency.
Local Genetic Sex Differences in Quantitative Traits
Abstract Many traits show small global sex differences in genetic correlations and heritability. However, how these differences are distributed across the genome remains unknown. Here, we use LAVA to test for local genetic sex differences in genetic correlations, heritabilities, and the magnitude of genetic effects across 157 quantitative traits in the UK Biobank. Nearly every trait shows evidence for sex-dimorphic effects in at least one locus.
Effect heterogeneity reveals complex pleiotropic effects of rare coding variants
Abstract Genome-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.
Rare variant aggregation highlights rare disease genes associated with brain volume variation
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).
Drinking motives and alcohol sensitivity mediate multi-dimensional genetic influences on alcohol use behaviors
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).
Multimodal brain imaging of insomnia, depression and anxiety symptoms: transdiagnostic commonalities and differences
Abstract Insomnia 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.
Simplifying causal gene identification in GWAS loci
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").
Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets - Nature Genetics
Abstract While 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.
Chromatin accessibility during human first-trimester neurodevelopment - Nature
Abstract The 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.
Refining the scope of genetic influences on alcohol misuse through environmental stratification and gene-environment interaction
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.
Investigating genetically stratified subgroups to better understand the etiology of alcohol misuse - Molecular Psychiatry
Sample Participants 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).
Addressing the ethical and societal challenges posed by genome-wide association studies of behavioral and brain-related traits - Nature Neuroscience
Abstract Genome-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.
Local Genetic Sex Differences in Quantitative Traits
Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website.
The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks
Results GWAS of RSN-SC and RSN-FC properties identify six genome-wide significant loci Following previously described procedures (Wei et al., 2019), we started our analysis by grouping cortical areas into seven RSN as defined by Yeo et al. (2011; visual, somatomotor, limbic, dorsal attention, ventral attention, frontoparietal, and default-mode network; Extended Data Fig.
Genome-wide association studies of polygenic risk score-derived phenotypes may lead to inflated false positive rates - Scientific Reports
Introduction arising from: C. Gouveia et al.; Scientific Reports https://doi.org/10.1038/s41598-022-12391-2 (2022). Gouveia and colleagues (2022)1 conducted a genome-wide association study (GWAS) of a polygenic risk score (PRS)-derived phenotype (N = 37,784), in which they identified 246 independent loci and 473 lead SNPs. This is an enormous increase compared to the most recent and largest GWAS of AD2 (N = 1,126,563), which identified 38 loci.
Exploring the genetic overlap between twelve psychiatric disorders - Nature Genetics
Author notes These authors jointly supervised this work: Mats Nagel, Sophie van der Sluis.
Genome-wide association studies of polygenic risk score-derived phenotypes may lead to inflated false positive rates
Contradictory Results doi: https://doi.org/10.1101/2022.09.10.507410 Abstract In a recent study, a polygenic risk score (PRS) for Alzheimer's disease was used to construct a new phenotype for a subsequent genome-wide association study (GWAS). Here we show that the applied method, in which the same genetic variants are used to construct the PRS-derived phenotype as well as to assess their effect in a GWAS of the same phenotype, leads to inflated false positive rates.
Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways - Nature Genetics
Abstract Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment currently exists. Previous genome-wide association studies with up to 1.3 million subjects identified over 200 associated loci. This extreme polygenicity suggested that many more loci remain to be discovered. The current study almost doubled the sample size to 593,724 cases and 1,771,286 controls, thereby increasing statistical power, and identified 554 risk loci (including 364 novel loci).
Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease - Nature Genetics
|
Correction to: Nature Genetics https://doi.org/10.1038/s41588-021-00921-z, published online 7 September 2021. In the version of this article initially published, the Acknowledgements section omitted the text “European Research Council advanced grant (grant no. ERC-2018-AdG GWAS2FUNC 834057 (to D.P.)),” which has now been included in the HTML and PDF versions of the article. Author information Author notes These authors contributed equally: Ole A. Andreassen, Danielle Posthuma.
By Jeanne E. Savage, Alexey Shadrin, Arvid Rongve, Sigrid Børte, Bendik S Winsvold, Cristen J. Willer, Geir Bråthen, Lars G. Fritsche, Laurent Thomas, Linda Pedersen, Wei Zhou, Petroula Proitsi, Angela Hodges, Richard J. B. Dobson, Latha Velayudhan, Julia M. Sealock, Lea K. Davis, Chandra A Reynolds, Hreinn Stefánsson, Anna Zettergren, Eystein Stordal, Ingvild Saltvedt, Srdjan Djurovic, Tormod Fladby, Geir Selbæk, Stephan Ripke, Kari Stefansson, Danielle Posthuma, Douglas P. Wightman, Sigurdur Magnusson
|
Nature
Verified
Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia - Nature Genetics
|
Abstract We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes.
By Duncan Palmer, Daniel P. Howrigan, Sinéad B. Chapman, Douglas H. Blackwood, Chia-Yen Chen, David Curtis, Nelson B. Freimer, Fernando S. Goes, Ian Jones, Lisa Jones, René S. Kahn, Mikael Landén, Adam E. Locke, Andrew McIntosh, Andrew Mcintosh, Andrew McQuillin, Derek Morris, Michael O’Donovan, Roel A. Ophoff, Michael Owen, Danielle Posthuma, Andreas Reif, Catherine A. Schaefer, Laura Scott, Tarjinder Singh, Jordan W. Smoller, Weiqing Wang, Benjamin M. Neale
|
Nature
Verified
Our faces and brains
Neurological, cognitive and genetic sciences share a longstanding interest in studying the relationship between the shape of the human skull and of the brain. However, the downstream biological genetic underpinnings of such interactions, if they exist, remain largely unknown. A new genetic study now reports on a set of genes that may be involved in substantially shaping the profile of our face and the physical shape of our brain, but not so much its capabilities. Fig.
Education, Religion, and Prosociality: A Study of Identical Twins
Loading citations... APA MLA Chicago Get more citations Cite as:
Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure
We use GSA implemented in MAGMA (v1.07), a detailed description of which can be found in De Leeuw et al.5. Briefly, the model is based on a linear regression framework with genes as data points, with the regression equation Z=β +Bβ +Sβ +ε, with \(\varepsilon \sim {\mathrm{MVN}}\left( {0,\sigma _e^2{\hat{\mathrm \Sigma }}} \right)\). Gene p-values P are first computed from the SNP data for each gene g .
Item-level analyses reveal genetic heterogeneity in neuroticism
The UK Biobank Study is a major data resource, containing phenotypic measures from 503,325 participants and genetic data from 489,212 participants (July 2017 release)15. The data was released in two phases (May 2015 and July 2017), and based on this we created two separate samples on which we performed the GWA analyses.
Functional mapping and annotation of genetic associations with FUMA
FUMA incorporates 18 biological data repositories and tools to process GWAS summary statistics and provide a variety of annotations (Supplementary Table 1). To accomplish this task, FUMA consists of two separate processes described in detail below.
Show More
loading
Actions
Is this you?
As a journalist, you can create a free Muck Rack account to customize your profile, list your contact preferences, and upload a portfolio of your best work.Get in touch with Danielle
Contact Danielle, search articles and posts on X, monitor coverage, and track replies from one place.
Learn more about Muck Rack