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Your search keyword '"Joel, Gelernter"' showing total 14 results
Start Over Author "Joel, Gelernter" Journal nature communications
14 results on '"Joel, Gelernter"'

1. Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction

Author

Alice Braun, Sudhanshu Shekhar, Daniel F. Levey, Peter Straub, Julia Kraft, Georgia M. Panagiotaropoulou, Karl Heilbron, Swapnil Awasthi, Rafael Meleka Hanna, Sarah Hoffmann, Maike Stein, Sophie Lehnerer, Philipp Mergenthaler, Abdelrahman G. Elnahas, Apostolia Topaloudi, Maria Koromina, Teemu Palviainen, Bergrun Asbjornsdottir, Hreinn Stefansson, Astros Th. Skuladóttir, Ingileif Jónsdóttir, Kari Stefansson, Kadri Reis, Tõnu Esko, Aarno Palotie, Frank Leypoldt, Murray B. Stein, Pierre Fontanillas, Estonian Biobank Research Team, andMe Research Team, Jaakko Kaprio, Joel Gelernter, Lea K. Davis, Peristera Paschou, Martijn R. Tannemaat, Jan J.G.M. Verschuuren, Gregor Kuhlenbäumer, Peter K. Gregersen, Maartje G. Huijbers, Frauke Stascheit, Andreas Meisel, and Stephan Ripke

Subjects
Science
Abstract

Abstract Myasthenia gravis (MG) is a rare autoantibody-mediated disease affecting the neuromuscular junction. We performed a genome-wide association study of 5708 MG cases and 432,028 controls of European ancestry and a replication study in 3989 cases and 226,643 controls provided by 23andMe Inc. We identified 12 independent genome-wide significant hits (P

Published
2024
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2. Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression

Author

Ruoyu Tian, Tian Ge, Hyeokmoon Kweon, Daniel B. Rocha, Max Lam, Jimmy Z. Liu, Kritika Singh, Biogen Biobank Team, Daniel F. Levey, Joel Gelernter, Murray B. Stein, Ellen A. Tsai, Hailiang Huang, Christopher F. Chabris, Todd Lencz, Heiko Runz, and Chia-Yen Chen

Subjects
Science
Abstract

Abstract Nearly two hundred common-variant depression risk loci have been identified by genome-wide association studies (GWAS). However, the impact of rare coding variants on depression remains poorly understood. Here, we present whole-exome sequencing analyses of depression with seven different definitions based on survey, questionnaire, and electronic health records in 320,356 UK Biobank participants. We showed that the burden of rare damaging coding variants in loss-of-function intolerant genes is significantly associated with risk of depression with various definitions. We compared the rare and common genetic architecture across depression definitions by genetic correlation and showed different genetic relationships between definitions across common and rare variants. In addition, we demonstrated that the effects of rare damaging coding variant burden and polygenic risk score on depression risk are additive. The gene set burden analyses revealed overlapping rare genetic variant components with developmental disorder, autism, and schizophrenia. Our study provides insights into the contribution of rare coding variants, separately and in conjunction with common variants, on depression with various definitions and their genetic relationships with neurodevelopmental disorders.

Published
2024
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3. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration

Author

Isabelle Austin-Zimmerman, Daniel F. Levey, Olga Giannakopoulou, Joseph D. Deak, Marco Galimberti, Keyrun Adhikari, Hang Zhou, Spiros Denaxas, Haritz Irizar, Karoline Kuchenbaecker, Andrew McQuillin, the Million Veteran Program, John Concato, Daniel J. Buysse, J. Michael Gaziano, Daniel J. Gottlieb, Renato Polimanti, Murray B. Stein, Elvira Bramon, and Joel Gelernter

Subjects
Science
Abstract

Abstract Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

Published
2023
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4. Profiling neuronal methylome and hydroxymethylome of opioid use disorder in the human orbitofrontal cortex

Author

Gregory Rompala, Sheila T. Nagamatsu, José Jaime Martínez-Magaña, Diana L. Nuñez-Ríos, Jiawei Wang, Matthew J. Girgenti, John H. Krystal, Joel Gelernter, Traumatic Stress Brain Research Group, Yasmin L. Hurd, and Janitza L. Montalvo-Ortiz

Subjects
Science
Abstract

Abstract Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD = 26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.

Published
2023
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5. Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology

Author

Max Lam, Chia-Yen Chen, W. David Hill, Charley Xia, Ruoyu Tian, Daniel F. Levey, Joel Gelernter, Murray B. Stein, Alexander S. Hatoum, Hailiang Huang, Anil K. Malhotra, Heiko Runz, Tian Ge, and Todd Lencz

Subjects
Science
Abstract

Cognitive impairments are a key feature of psychopathology. Here, authors exploit the genetic overlap between cognitive dimensions and psychopathology to parse the biology of psychiatric illness and identify “meta-loci” genome segments characterized by specific patterns of overlap.

Published
2022
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6. Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells

Author

Mary-Ellen Lynall, Blagoje Soskic, James Hayhurst, Jeremy Schwartzentruber, Daniel F. Levey, Gita A. Pathak, Renato Polimanti, Joel Gelernter, Murray B. Stein, Gosia Trynka, Menna R. Clatworthy, and Ed Bullmore

Subjects
Science
Abstract

The role of the immune system in the pathogenesis of psychiatric disorders is unclear. Here, the authors show that genetic risk variants for multiple psychiatric disorders are enriched in regions of the genome active in the brain and in lymphoid cells, especially stimulated T cells, but not in myeloid cells.

Published
2022
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7. Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

Author

Bryan C. Quach, Michael J. Bray, Nathan C. Gaddis, Mengzhen Liu, Teemu Palviainen, Camelia C. Minica, Stephanie Zellers, Richard Sherva, Fazil Aliev, Michael Nothnagel, Kendra A. Young, Jesse A. Marks, Hannah Young, Megan U. Carnes, Yuelong Guo, Alex Waldrop, Nancy Y. A. Sey, Maria T. Landi, Daniel W. McNeil, Dmitriy Drichel, Lindsay A. Farrer, Christina A. Markunas, Jacqueline M. Vink, Jouke-Jan Hottenga, William G. Iacono, Henry R. Kranzler, Nancy L. Saccone, Michael C. Neale, Pamela Madden, Marcella Rietschel, Mary L. Marazita, Matthew McGue, Hyejung Won, Georg Winterer, Richard Grucza, Danielle M. Dick, Joel Gelernter, Neil E. Caporaso, Timothy B. Baker, Dorret I. Boomsma, Jaakko Kaprio, John E. Hokanson, Scott Vrieze, Laura J. Bierut, Eric O. Johnson, and Dana B. Hancock

Subjects
Science
Abstract

There is strong genetic evidence for cigarette smoking behaviors, yet little is known on nicotine dependence (ND). Here, the authors perform a genome-wide association study on ND in 58,000 smokers, identifying five genome-wide significant loci.

Published
2020
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8. Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals

Author

Ke Xu, Boyang Li, Kathleen A. McGinnis, Rachel Vickers-Smith, Cecilia Dao, Ning Sun, Rachel L. Kember, Hang Zhou, William C. Becker, Joel Gelernter, Henry R. Kranzler, Hongyu Zhao, Amy C. Justice, and VA Million Veteran Program

Subjects
Science
Abstract

Genome-wide association studies (GWASs) for cigarette smoking have identified several hundred loci that account for a small proportion of the overall genetic risk. Here, the authors report a large GWAS for smoking trajectories and meta-analysis for smoking status, finding multiple plausible loci.

Published
2020
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9. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author

Caroline M. Nievergelt, Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, Jonathan R. I. Coleman, Shareefa Dalvie, Laramie E. Duncan, Joel Gelernter, Daniel F. Levey, Mark W. Logue, Renato Polimanti, Allison C. Provost, Andrew Ratanatharathorn, Murray B. Stein, Katy Torres, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Søren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Dragan Babić, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Anders D. Børglum, Bekh Bradley, Megan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, José M. Caldas- de- Almeida, Anders M. Dale, Mark J. Daly, Nikolaos P. Daskalakis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Alma Dzubur-Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Elbert Geuze, Charles Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Supriya Harnal, Michael A. Hauser, Andrew C. Heath, Sian M. J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Angela G. Junglen, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A. M. Lebois, Catrin E. Lewis, Sarah D. Linnstaedt, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica Maples-Keller, Charles Marmar, Alicia R. Martin, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Sarah McLeay, Divya Mehta, William P. Milberg, Mark W. Miller, Rajendra A. Morey, Charles Phillip Morris, Ole Mors, Preben B. Mortensen, Benjamin M. Neale, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Stephan Ripke, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Ken Ruggiero, Ariane Rung, Bart P. F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Jonathan D. Wolff, Rachel Yehuda, Ross McD. Young, Keith A. Young, Hongyu Zhao, Lori A. Zoellner, Israel Liberzon, Kerry J. Ressler, Magali Haas, and Karestan C. Koenen

Subjects
Science
Abstract

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Published
2019
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10. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Author

Henry R. Kranzler, Hang Zhou, Rachel L. Kember, Rachel Vickers Smith, Amy C. Justice, Scott Damrauer, Philip S. Tsao, Derek Klarin, Aris Baras, Jeffrey Reid, John Overton, Daniel J. Rader, Zhongshan Cheng, Janet P. Tate, William C. Becker, John Concato, Ke Xu, Renato Polimanti, Hongyu Zhao, and Joel Gelernter

Subjects
Science
Abstract

The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.

Published
2019
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11. Author Correction: Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Author

Henry R. Kranzler, Hang Zhou, Rachel L. Kember, Rachel Vickers Smith, Amy C. Justice, Scott Damrauer, Philip S. Tsao, Derek Klarin, Aris Baras, Jeffrey Reid, John Overton, Daniel J. Rader, Zhongshan Cheng, Janet P. Tate, William C. Becker, John Concato, Ke Xu, Renato Polimanti, Hongyu Zhao, and Joel Gelernter

Subjects
Science
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019
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12. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Author

Zhongshan Cheng, Jeffrey S. Reid, Aris Baras, Ke Xu, William C. Becker, Philip S. Tsao, Daniel J. Rader, Derek Klarin, Scott M. Damrauer, Joel Gelernter, Renato Polimanti, Hang Zhou, Amy C. Justice, Hongyu Zhao, Henry R. Kranzler, John D. Overton, Rachel Vickers Smith, John Concato, Janet P. Tate, and Rachel L. Kember

Subjects
Adult, Male, 0301 basic medicine, Multifactorial Inheritance, Alcohol Drinking, Epidemiology, Science, Addiction, General Physics and Astronomy, Genome-wide association study, 02 engineering and technology, Alcohol use disorder, Biology, Polymorphism, Single Nucleotide, Genome-wide association studies, Genetic correlation, Article, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, Genetics research, mental disorders, medicine, Humans, Longitudinal Studies, Risk factor, Young adult, Author Correction, lcsh:Science, Aged, Genetic association, Aged, 80 and over, Multidisciplinary, General Chemistry, Middle Aged, Heritability, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, Alcoholism, Phenotype, 030104 developmental biology, Female, lcsh:Q, 0210 nano-technology, Genome-Wide Association Study, Demography
Abstract

Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample (N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder., The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.

Published
2019

13. Author Correction: Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Author

Derek Klarin, Daniel J. Rader, Amy C. Justice, Zhongshan Cheng, Philip S. Tsao, Aris Baras, Joel Gelernter, Scott M. Damrauer, Jeffrey S. Reid, Ke Xu, Rachel L. Kember, Renato Polimanti, Hang Zhou, Hongyu Zhao, William C. Becker, Janet P. Tate, Henry R. Kranzler, John D. Overton, Rachel Vickers Smith, and John Concato

Subjects
0301 basic medicine, medicine.medical_specialty, Epidemiology, Science, MEDLINE, General Physics and Astronomy, Addiction, Genome-wide association study, 02 engineering and technology, Genome-wide association studies, General Biochemistry, Genetics and Molecular Biology, GeneralLiterature_MISCELLANEOUS, 03 medical and health sciences, Genetics research, medicine, Center (algebra and category theory), Psychiatry, Author Correction, lcsh:Science, health care economics and organizations, Service (business), Multidisciplinary, Published Erratum, General Chemistry, 021001 nanoscience & nanotechnology, Mental illness, medicine.disease, humanities, 030104 developmental biology, ComputingMilieux_COMPUTERSANDSOCIETY, lcsh:Q, 0210 nano-technology, Psychology, Alcohol consumption
Abstract

The original version of this Article omitted the following from the Acknowledgements: ‘Supported by the Mental Illness Research, Education and Clinical Center of the Veterans Integrated Service Network 4 of the Department of Veterans Affairs.’ This has now been corrected in both the PDF and HTML versions of the Article.

Published
2019

14. Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals

Author

William C. Becker, Rachel Vickers-Smith, Cecilia Dao, Henry R. Kranzler, Amy C. Justice, Ke Xu, Kathleen A. McGinnis, VA Million Veteran Program, Hongyu Zhao, Hang Zhou, Joel Gelernter, Ning Sun, Boyang Li, and Rachel L. Kember

Subjects
0301 basic medicine, Male, Science, medicine.medical_treatment, Quantitative Trait Loci, General Physics and Astronomy, Genetic predisposition to disease, Locus (genetics), Genome-wide association study, Predictive markers, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, White People, Article, Nicotine, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Longitudinal Studies, lcsh:Science, Genetic association, Multidisciplinary, business.industry, Smoking, General Chemistry, Hispanic or Latino, Middle Aged, Black or African American, 030104 developmental biology, Risk factors, Meta-analysis, Expression quantitative trait loci, Smoking cessation, Smoking status, lcsh:Q, Female, business, 030217 neurology & neurosurgery, Demography, medicine.drug, Genome-Wide Association Study
Abstract

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (Ntotal = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior., Genome-wide association studies (GWASs) for cigarette smoking have identified several hundred loci that account for a small proportion of the overall genetic risk. Here, the authors report a large GWAS for smoking trajectories and meta-analysis for smoking status, finding multiple plausible loci.

Published
2019

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