Search

Your search keyword '"Roussos P"' showing total 30 results
Start Over Author "Roussos P" Journal nature communications
30 results on '"Roussos P"'

1. A multi-regional human brain atlas of chromatin accessibility and gene expression facilitates promoter-isoform resolution genetic fine-mapping

Author

Pengfei Dong, Liting Song, Jaroslav Bendl, Ruth Misir, Zhiping Shao, Jonathan Edelstien, David A. Davis, Vahram Haroutunian, William K. Scott, Susanne Acker, Nathan Lawless, Gabriel E. Hoffman, John F. Fullard, and Panos Roussos

Subjects
Science
Abstract

Abstract Brain region- and cell-specific transcriptomic and epigenomic features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression profiles in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions. Genes with distinct promoter-isoform usage across brain regions were strongly enriched for neuropsychiatric disease risk variants. Moreover, we built enhancer-promoter interactions at promoter-isoform resolution across different brain regions and highlighted the contribution of brain region-specific and promoter-isoform-specific regulation to neuropsychiatric disorders. Including promoter-isoform resolution uncovers additional distal elements implicated in the heritability of diseases, thereby increasing the power to fine-map risk genes. Our results provide a valuable resource for studying molecular regulation across multiple regions of the human brain and underscore the importance of considering isoform information in gene regulation.

Published
2024
Full Text
View/download PDF

3. Author Correction: Divergent landscapes of A-to-I editing in postmortem and living human brain

Author

Rodriguez de los Santos, Miguel, Kopell, Brian H., Buxbaum Grice, Ariela, Ganesh, Gauri, Yang, Andy, Amini, Pardis, Liharska, Lora E., Vornholt, Eric, Fullard, John F., Dong, Pengfei, Park, Eric, Zipkowitz, Sarah, Kaji, Deepak A., Thompson, Ryan C., Liu, Donjing, Park, You Jeong, Cheng, Esther, Ziafat, Kimia, Moya, Emily, Fennessy, Brian, Wilkins, Lillian, Silk, Hannah, Linares, Lisa M., Sullivan, Brendan, Cohen, Vanessa, Kota, Prashant, Feng, Claudia, Johnson, Jessica S., Rieder, Marysia-Kolbe, Scarpa, Joseph, Nadkarni, Girish N., Wang, Minghui, Zhang, Bin, Sklar, Pamela, Beckmann, Noam D., Schadt, Eric E., Roussos, Panos, Charney, Alexander W., and Breen, Michael S.

Published
2024
Full Text
View/download PDF

5. Divergent landscapes of A-to-I editing in postmortem and living human brain

Author

Rodriguez de los Santos, Miguel, Kopell, Brian H., Buxbaum Grice, Ariela, Ganesh, Gauri, Yang, Andy, Amini, Pardis, Liharska, Lora E., Vornholt, Eric, Fullard, John F., Dong, Pengfei, Park, Eric, Zipkowitz, Sarah, Kaji, Deepak A., Thompson, Ryan C., Liu, Donjing, Park, You Jeong, Cheng, Esther, Ziafat, Kimia, Moya, Emily, Fennessy, Brian, Wilkins, Lillian, Silk, Hannah, Linares, Lisa M., Sullivan, Brendan, Cohen, Vanessa, Kota, Prashant, Feng, Claudia, Johnson, Jessica S., Rieder, Marysia-Kolbe, Scarpa, Joseph, Nadkarni, Girish N., Wang, Minghui, Zhang, Bin, Sklar, Pamela, Beckmann, Noam D., Schadt, Eric E., Roussos, Panos, Charney, Alexander W., and Breen, Michael S.

Published
2024
Full Text
View/download PDF

6. Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease

Author

Qi Wang, Jerry Antone, Eric Alsop, Rebecca Reiman, Cory Funk, Jaroslav Bendl, Joel T. Dudley, Winnie S. Liang, Timothy L. Karr, Panos Roussos, David A. Bennett, Philip L. De Jager, Geidy E. Serrano, Thomas G. Beach, Kendall Van Keuren-Jensen, Diego Mastroeni, Eric M. Reiman, and Benjamin P. Readhead

Subjects
Science
Abstract

Abstract The emergence of single nucleus RNA sequencing (snRNA-seq) offers to revolutionize the study of Alzheimer’s disease (AD). Integration with complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link cell subpopulations and molecular networks with a broader disease-relevant context. We report snRNA-seq profiles from superior frontal gyrus samples from 101 well characterized subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants with CR1 expression in oligodendrocytes as well as alterations in hematological parameters. We observed an AD-associated CD83(+) microglial subtype with unique molecular networks and which is associated with immunoglobulin IgG4 production in the transverse colon. Our major observations were replicated in two additional, independent snRNA-seq data sets. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal disease biology.

Published
2024
Full Text
View/download PDF

7. Divergent landscapes of A-to-I editing in postmortem and living human brain

Author

Miguel Rodriguez de los Santos, Brian H. Kopell, Ariela Buxbaum Grice, Gauri Ganesh, Andy Yang, Pardis Amini, Lora E. Liharska, Eric Vornholt, John F. Fullard, Pengfei Dong, Eric Park, Sarah Zipkowitz, Deepak A. Kaji, Ryan C. Thompson, Donjing Liu, You Jeong Park, Esther Cheng, Kimia Ziafat, Emily Moya, Brian Fennessy, Lillian Wilkins, Hannah Silk, Lisa M. Linares, Brendan Sullivan, Vanessa Cohen, Prashant Kota, Claudia Feng, Jessica S. Johnson, Marysia-Kolbe Rieder, Joseph Scarpa, Girish N. Nadkarni, Minghui Wang, Bin Zhang, Pamela Sklar, Noam D. Beckmann, Eric E. Schadt, Panos Roussos, Alexander W. Charney, and Michael S. Breen

Subjects
Science
Abstract

Abstract Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.

Published
2024
Full Text
View/download PDF

8. Author Correction: Divergent landscapes of A-to-I editing in postmortem and living human brain

Author

Miguel Rodriguez de los Santos, Brian H. Kopell, Ariela Buxbaum Grice, Gauri Ganesh, Andy Yang, Pardis Amini, Lora E. Liharska, Eric Vornholt, John F. Fullard, Pengfei Dong, Eric Park, Sarah Zipkowitz, Deepak A. Kaji, Ryan C. Thompson, Donjing Liu, You Jeong Park, Esther Cheng, Kimia Ziafat, Emily Moya, Brian Fennessy, Lillian Wilkins, Hannah Silk, Lisa M. Linares, Brendan Sullivan, Vanessa Cohen, Prashant Kota, Claudia Feng, Jessica S. Johnson, Marysia-Kolbe Rieder, Joseph Scarpa, Girish N. Nadkarni, Minghui Wang, Bin Zhang, Pamela Sklar, Noam D. Beckmann, Eric E. Schadt, Panos Roussos, Alexander W. Charney, and Michael S. Breen

Subjects
Science
Published
2024
Full Text
View/download PDF

9. Integration of Alzheimer’s disease genetics and myeloid genomics identifies disease risk regulatory elements and genes

Author

Novikova, Gloriia, Kapoor, Manav, TCW, Julia, Abud, Edsel M, Efthymiou, Anastasia G, Chen, Steven X, Cheng, Haoxiang, Fullard, John F, Bendl, Jaroslav, Liu, Yiyuan, Roussos, Panos, Björkegren, Johan LM, Liu, Yunlong, Poon, Wayne W, Hao, Ke, Marcora, Edoardo, and Goate, Alison M

Subjects
Biological Sciences, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Dementia, Alzheimer's Disease, Aging, Stem Cell Research, Human Genome, Biotechnology, Prevention, Brain Disorders, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alleles, Alzheimer Disease, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Induced Pluripotent Stem Cells, Macrophages, Microglia, Myeloid Cells, Regulatory Sequences, Nucleic Acid, Transcriptome
Abstract

Genome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer's disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that AD risk alleles are enriched in myeloid-specific epigenomic annotations. Here, we show that they are specifically enriched in active enhancers of monocytes, macrophages and microglia. We integrated AD GWAS with myeloid epigenomic and transcriptomic datasets using analytical approaches to link myeloid enhancer activity to target gene expression regulation and AD risk modification. We identify AD risk enhancers and nominate candidate causal genes among their likely targets (including AP4E1, AP4M1, APBB3, BIN1, MS4A4A, MS4A6A, PILRA, RABEP1, SPI1, TP53INP1, and ZYX) in twenty loci. Fine-mapping of these enhancers nominates candidate functional variants that likely modify AD risk by regulating gene expression in myeloid cells. In the MS4A locus we identified a single candidate functional variant and validated it in human induced pluripotent stem cell (hiPSC)-derived microglia and brain. Taken together, this study integrates AD GWAS with multiple myeloid genomic datasets to investigate the mechanisms of AD risk alleles and nominates candidate functional variants, regulatory elements and genes that likely modulate disease susceptibility.

Published
2021

10. Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome

Author

Sasha L. Fulton, Wendy Wenderski, Ashley E. Lepack, Andrew L. Eagle, Tomas Fanutza, Ryan M. Bastle, Aarthi Ramakrishnan, Emma C. Hays, Arianna Neal, Jaroslav Bendl, Lorna A. Farrelly, Amni Al-Kachak, Yang Lyu, Bulent Cetin, Jennifer C. Chan, Tina N. Tran, Rachael L. Neve, Randall J. Roper, Kristen J. Brennand, Panos Roussos, John C. Schimenti, Allyson K. Friedman, Li Shen, Robert D. Blitzer, Alfred J. Robison, Gerald R. Crabtree, and Ian Maze

Subjects
Science
Abstract

The molecular mechanisms underlying deficits in Down syndrome remain unclear. Here, the authors show that copy number restoration of a chromatin remodeler in trisomic mice is sufficient to rescue epigenomic, physiological and cognitive deficits.

Published
2022
Full Text
View/download PDF

11. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

Author

Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S, Finan, Chris, Bis, Joshua C, Huntley, Rachael P, Lovering, Ruth C, Tajuddin, Salman M, Winkler, Thomas W, Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V, Hofer, Edith, van Leeuwen, Elisabeth M, Nolte, Ilja M, Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkänen, Niina, Franzén, Oscar, Joshi, Peter K, Noordam, Raymond, Marioni, Riccardo E, Hwang, Shih-Jen, Musani, Solomon K, Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B, Hofman, Albert, Teumer, Alexander, Cox, Amanda J, Uitterlinden, André G, Wong, Andrew, Smit, Andries J, Newman, Anne B, Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W, Langefeld, Carl D, Wassel, Christina L, Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H, Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E, Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Völzke, Henry, Markus, Hugh S, Deary, Ian J, Jukema, J Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C, Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D, Dhana, Klodian, Kiemeney, Lambertus ALM, Lind, Lars, Raffield, Laura M, Launer, Lenore J, Holdt, Lesca M, Dörr, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A, Melander, Olle, Raitakari, Olli, Franco, Oscar H, Rueda-Ochoa, Oscar L, Roussos, Panos, Whincup, Peter H, Amouyel, Philippe, and Giral, Philippe

Subjects
MEGASTROKE Consortium, Humans, Coronary Disease, Genetic Predisposition to Disease, Amino Acid Oxidoreductases, Protein-Lysine 6-Oxidase, Risk Factors, Lod Score, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Plaque, Atherosclerotic, Carotid Intima-Media Thickness, ADAMTS9 Protein, Plaque, Atherosclerotic, Polymorphism, Single Nucleotide
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018

12. Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome

Author

Fulton, Sasha L., Wenderski, Wendy, Lepack, Ashley E., Eagle, Andrew L., Fanutza, Tomas, Bastle, Ryan M., Ramakrishnan, Aarthi, Hays, Emma C., Neal, Arianna, Bendl, Jaroslav, Farrelly, Lorna A., Al-Kachak, Amni, Lyu, Yang, Cetin, Bulent, Chan, Jennifer C., Tran, Tina N., Neve, Rachael L., Roper, Randall J., Brennand, Kristen J., Roussos, Panos, Schimenti, John C., Friedman, Allyson K., Shen, Li, Blitzer, Robert D., Robison, Alfred J., Crabtree, Gerald R., and Maze, Ian

Published
2022
Full Text
View/download PDF

13. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children

Author

Noam D. Beckmann, Phillip H. Comella, Esther Cheng, Lauren Lepow, Aviva G. Beckmann, Scott R. Tyler, Konstantinos Mouskas, Nicole W. Simons, Gabriel E. Hoffman, Nancy J. Francoeur, Diane Marie Del Valle, Gurpawan Kang, Anh Do, Emily Moya, Lillian Wilkins, Jessica Le Berichel, Christie Chang, Robert Marvin, Sharlene Calorossi, Alona Lansky, Laura Walker, Nancy Yi, Alex Yu, Jonathan Chung, Matthew Hartnett, Melody Eaton, Sandra Hatem, Hajra Jamal, Alara Akyatan, Alexandra Tabachnikova, Lora E. Liharska, Liam Cotter, Brian Fennessy, Akhil Vaid, Guillermo Barturen, Hardik Shah, Ying-chih Wang, Shwetha Hara Sridhar, Juan Soto, Swaroop Bose, Kent Madrid, Ethan Ellis, Elyze Merzier, Konstantinos Vlachos, Nataly Fishman, Manying Tin, Melissa Smith, Hui Xie, Manishkumar Patel, Kai Nie, Kimberly Argueta, Jocelyn Harris, Neha Karekar, Craig Batchelor, Jose Lacunza, Mahlet Yishak, Kevin Tuballes, Ieisha Scott, Arvind Kumar, Suraj Jaladanki, Charuta Agashe, Ryan Thompson, Evan Clark, Bojan Losic, Lauren Peters, The Mount Sinai COVID-19 Biobank Team, Panagiotis Roussos, Jun Zhu, Wenhui Wang, Andrew Kasarskis, Benjamin S. Glicksberg, Girish Nadkarni, Dusan Bogunovic, Cordelia Elaiho, Sandeep Gangadharan, George Ofori-Amanfo, Kasey Alesso-Carra, Kenan Onel, Karen M. Wilson, Carmen Argmann, Supinda Bunyavanich, Marta E. Alarcón-Riquelme, Thomas U. Marron, Adeeb Rahman, Seunghee Kim-Schulze, Sacha Gnjatic, Bruce D. Gelb, Miriam Merad, Robert Sebra, Eric E. Schadt, and Alexander W. Charney

Subjects
Science
Abstract

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Published
2021
Full Text
View/download PDF

14. Integration of Alzheimer’s disease genetics and myeloid genomics identifies disease risk regulatory elements and genes

Author

Gloriia Novikova, Manav Kapoor, Julia TCW, Edsel M. Abud, Anastasia G. Efthymiou, Steven X. Chen, Haoxiang Cheng, John F. Fullard, Jaroslav Bendl, Yiyuan Liu, Panos Roussos, Johan LM Björkegren, Yunlong Liu, Wayne W. Poon, Ke Hao, Edoardo Marcora, and Alison M. Goate

Subjects
Science
Abstract

This study integrates Alzheimer’s disease (AD) GWAS data with myeloid cell genomics, and reports that myeloid active enhancers are most burdened by AD risk alleles. The authors also nominate candidate causal regulatory elements, variants and genes that likely modulate the risk for AD.

Published
2021
Full Text
View/download PDF

15. Common schizophrenia risk variants are enriched in open chromatin regions of human glutamatergic neurons

Author

Mads E. Hauberg, Jordi Creus-Muncunill, Jaroslav Bendl, Alexey Kozlenkov, Biao Zeng, Chuhyon Corwin, Sarah Chowdhury, Harald Kranz, Yasmin L. Hurd, Michael Wegner, Anders D. Børglum, Stella Dracheva, Michelle E. Ehrlich, John F. Fullard, and Panos Roussos

Subjects
Science
Abstract

Here, the authors perform ATAC-seq on four distinct cell populations from three different regions of the human brain, finding that chromatin accessibility varies greatly by cell type and less by brain region. This study reveals differences in biological function and gene regulation, as well as overlap of genetic variants associated with schizophrenia and other neuropsychiatric traits.

Published
2020
Full Text
View/download PDF

16. Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder

Author

Gabor Egervari, Diana Akpoyibo, Tanni Rahman, John F. Fullard, James E. Callens, Joseph A. Landry, Annie Ly, Xianxiao Zhou, Noël Warren, Mads E. Hauberg, Gabriel Hoffman, Randy Ellis, Jacqueline-Marie N. Ferland, Michael L. Miller, Eva Keller, Bin Zhang, Panos Roussos, and Yasmin L. Hurd

Subjects
Science
Abstract

Epigenetic mechanisms have emerged as contributors to the molecular impairments caused by exposure to environmental factors such as abused substances. Here the authors perform epigenetic profiling of the striatum and identify the tyrosine kinase FYN is an important driver of neurodegenerative-like pathology and drug-taking behaviour.

Published
2020
Full Text
View/download PDF

17. Functional annotation of rare structural variation in the human brain

Author

Lide Han, Xuefang Zhao, Mary Lauren Benton, Thaneer Perumal, Ryan L. Collins, Gabriel E. Hoffman, Jessica S. Johnson, Laura Sloofman, Harold Z. Wang, Matthew R. Stone, CommonMind Consortium, Kristen J. Brennand, Harrison Brand, Solveig K. Sieberts, Stefano Marenco, Mette A. Peters, Barbara K. Lipska, Panos Roussos, John A. Capra, Michael Talkowski, and Douglas M. Ruderfer

Subjects
Science
Abstract

Structural variants (SVs) contribute to the genetic architecture of many brain-related disorders. Here, the authors integrate SV calls from genome sequencing (n = 755) with RNA-seq data (n = 629) from post-mortem dorsal lateral prefrontal cortex to annotate the gene regulatory effects of SVs in the human brain and their potential to contribute to disease.

Published
2020
Full Text
View/download PDF

18. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children

Author

Beckmann, Noam D., Comella, Phillip H., Cheng, Esther, Lepow, Lauren, Beckmann, Aviva G., Tyler, Scott R., Mouskas, Konstantinos, Simons, Nicole W., Hoffman, Gabriel E., Francoeur, Nancy J., Del Valle, Diane Marie, Kang, Gurpawan, Do, Anh, Moya, Emily, Wilkins, Lillian, Le Berichel, Jessica, Chang, Christie, Marvin, Robert, Calorossi, Sharlene, Lansky, Alona, Walker, Laura, Yi, Nancy, Yu, Alex, Chung, Jonathan, Hartnett, Matthew, Eaton, Melody, Hatem, Sandra, Jamal, Hajra, Akyatan, Alara, Tabachnikova, Alexandra, Liharska, Lora E., Cotter, Liam, Fennessy, Brian, Vaid, Akhil, Barturen, Guillermo, Shah, Hardik, Wang, Ying-chih, Sridhar, Shwetha Hara, Soto, Juan, Bose, Swaroop, Madrid, Kent, Ellis, Ethan, Merzier, Elyze, Vlachos, Konstantinos, Fishman, Nataly, Tin, Manying, Smith, Melissa, Xie, Hui, Patel, Manishkumar, Nie, Kai, Argueta, Kimberly, Harris, Jocelyn, Karekar, Neha, Batchelor, Craig, Lacunza, Jose, Yishak, Mahlet, Tuballes, Kevin, Scott, Ieisha, Kumar, Arvind, Jaladanki, Suraj, Agashe, Charuta, Thompson, Ryan, Clark, Evan, Losic, Bojan, Peters, Lauren, Roussos, Panagiotis, Zhu, Jun, Wang, Wenhui, Kasarskis, Andrew, Glicksberg, Benjamin S., Nadkarni, Girish, Bogunovic, Dusan, Elaiho, Cordelia, Gangadharan, Sandeep, Ofori-Amanfo, George, Alesso-Carra, Kasey, Onel, Kenan, Wilson, Karen M., Argmann, Carmen, Bunyavanich, Supinda, Alarcón-Riquelme, Marta E., Marron, Thomas U., Rahman, Adeeb, Kim-Schulze, Seunghee, Gnjatic, Sacha, Gelb, Bruce D., Merad, Miriam, Sebra, Robert, Schadt, Eric E., and Charney, Alexander W.

Published
2021
Full Text
View/download PDF

19. Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits

Author

Wen Zhang, Georgios Voloudakis, Veera M. Rajagopal, Ben Readhead, Joel T. Dudley, Eric E. Schadt, Johan L. M. Björkegren, Yungil Kim, John F. Fullard, Gabriel E. Hoffman, and Panos Roussos

Subjects
Science
Abstract

PrediXcan is a widely used gene expression imputation method that links genetic variants to gene expression. Here, the authors develop EpiXcan which leverages epigenetic annotations to inform transcriptomic imputation and further use the obtained gene-trait associations for computational drug repurposing.

Published
2019
Full Text
View/download PDF

20. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Christina M. Lill, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, and Ian J. Deary

Subjects
Science
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Published
2019
Full Text
View/download PDF

21. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Nora Franceschini, Claudia Giambartolomei, Paul S. de Vries, Chris Finan, Joshua C. Bis, Rachael P. Huntley, Ruth C. Lovering, Salman M. Tajuddin, Thomas W. Winkler, Misa Graff, Maryam Kavousi, Caroline Dale, Albert V. Smith, Edith Hofer, Elisabeth M. van Leeuwen, Ilja M. Nolte, Lingyi Lu, Markus Scholz, Muralidharan Sargurupremraj, Niina Pitkänen, Oscar Franzén, Peter K. Joshi, Raymond Noordam, Riccardo E. Marioni, Shih-Jen Hwang, Solomon K. Musani, Ulf Schminke, Walter Palmas, Aaron Isaacs, Adolfo Correa, Alan B. Zonderman, Albert Hofman, Alexander Teumer, Amanda J. Cox, André G. Uitterlinden, Andrew Wong, Andries J. Smit, Anne B. Newman, Annie Britton, Arno Ruusalepp, Bengt Sennblad, Bo Hedblad, Bogdan Pasaniuc, Brenda W. Penninx, Carl D. Langefeld, Christina L. Wassel, Christophe Tzourio, Cristiano Fava, Damiano Baldassarre, Daniel H. O’Leary, Daniel Teupser, Diana Kuh, Elena Tremoli, Elmo Mannarino, Enzo Grossi, Eric Boerwinkle, Eric E. Schadt, Erik Ingelsson, Fabrizio Veglia, Fernando Rivadeneira, Frank Beutner, Ganesh Chauhan, Gerardo Heiss, Harold Snieder, Harry Campbell, Henry Völzke, Hugh S. Markus, Ian J. Deary, J. Wouter Jukema, Jacqueline de Graaf, Jacqueline Price, Janne Pott, Jemma C. Hopewell, Jingjing Liang, Joachim Thiery, Jorgen Engmann, Karl Gertow, Kenneth Rice, Kent D. Taylor, Klodian Dhana, Lambertus A. L. M. Kiemeney, Lars Lind, Laura M. Raffield, Lenore J. Launer, Lesca M. Holdt, Marcus Dörr, Martin Dichgans, Matthew Traylor, Matthias Sitzer, Meena Kumari, Mika Kivimaki, Mike A. Nalls, Olle Melander, Olli Raitakari, Oscar H. Franco, Oscar L. Rueda-Ochoa, Panos Roussos, Peter H. Whincup, Philippe Amouyel, Philippe Giral, Pramod Anugu, Quenna Wong, Rainer Malik, Rainer Rauramaa, Ralph Burkhardt, Rebecca Hardy, Reinhold Schmidt, Renée de Mutsert, Richard W. Morris, Rona J. Strawbridge, S. Goya Wannamethee, Sara Hägg, Sonia Shah, Stela McLachlan, Stella Trompet, Sudha Seshadri, Sudhir Kurl, Susan R. Heckbert, Susan Ring, Tamara B. Harris, Terho Lehtimäki, Tessel E. Galesloot, Tina Shah, Ulf de Faire, Vincent Plagnol, Wayne D. Rosamond, Wendy Post, Xiaofeng Zhu, Xiaoling Zhang, Xiuqing Guo, Yasaman Saba, MEGASTROKE Consortium, Abbas Dehghan, Adrie Seldenrijk, Alanna C. Morrison, Anders Hamsten, Bruce M. Psaty, Cornelia M. van Duijn, Deborah A. Lawlor, Dennis O. Mook-Kanamori, Donald W. Bowden, Helena Schmidt, James F. Wilson, James G. Wilson, Jerome I. Rotter, Joanna M. Wardlaw, John Deanfield, Julian Halcox, Leo-Pekka Lyytikäinen, Markus Loeffler, Michele K. Evans, Stéphanie Debette, Steve E. Humphries, Uwe Völker, Vilmundur Gudnason, Aroon D. Hingorani, Johan L. M. Björkegren, Juan P. Casas, and Christopher J. O’Donnell

Subjects
Science
Abstract

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Published
2018
Full Text
View/download PDF

22. Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia

Author

Julien Bryois, Melanie E. Garrett, Lingyun Song, Alexias Safi, Paola Giusti-Rodriguez, Graham D. Johnson, Annie W. Shieh, Alfonso Buil, John F. Fullard, Panos Roussos, Pamela Sklar, Schahram Akbarian, Vahram Haroutunian, Craig A. Stockmeier, Gregory A. Wray, Kevin P. White, Chunyu Liu, Timothy E. Reddy, Allison Ashley-Koch, Patrick F. Sullivan, and Gregory E. Crawford

Subjects
Science
Abstract

Chromatin accessibility may be altered in disease states. Here the authors carry out ATAC-seq on a large number of samples of dorsolateral prefrontal cortex from individuals with schizophrenia, and healthy controls.

Published
2018
Full Text
View/download PDF

23. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Christina M. Lill, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, and Ian J. Deary

Subjects
Science
Abstract

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Published
2018
Full Text
View/download PDF

26. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Böhmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kähönen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M., Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Jr, Will T., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hägg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Räikkönen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Jr, Thomas H., Bressler, Jan, Lencz, Todd, and Deary, Ian J.

Published
2019
Full Text
View/download PDF

27. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Böhmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kähönen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M., Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Jr, Will T., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hägg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Räikkönen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Jr, Thomas H., Bressler, Jan, Lencz, Todd, and Deary, Ian J.

Published
2018
Full Text
View/download PDF

28. Functional annotation of rare structural variation in the human brain.

Author

Han L, Zhao X, Benton ML, Perumal T, Collins RL, Hoffman GE, Johnson JS, Sloofman L, Wang HZ, Stone MR, Brennand KJ, Brand H, Sieberts SK, Marenco S, Peters MA, Lipska BK, Roussos P, Capra JA, Talkowski M, and Ruderfer DM

Subjects
Autopsy methods, Brain pathology, Female, Gene Expression Profiling methods, Humans, Male, Neurodevelopmental Disorders genetics, Sequence Analysis, RNA methods, Brain metabolism, DNA Copy Number Variations, Gene Expression Regulation, Genetic Variation, Genome, Human genetics
Abstract

Structural variants (SVs) contribute to many disorders, yet, functionally annotating them remains a major challenge. Here, we integrate SVs with RNA-sequencing from human post-mortem brains to quantify their dosage and regulatory effects. We show that genic and regulatory SVs exist at significantly lower frequencies than intergenic SVs. Functional impact of copy number variants (CNVs) stems from both the proportion of genic and regulatory content altered and loss-of-function intolerance of the gene. We train a linear model to predict expression effects of rare CNVs and use it to annotate regulatory disruption of CNVs from 14,891 independent genome-sequenced individuals. Pathogenic deletions implicated in neurodevelopmental disorders show significantly more extreme regulatory disruption scores and if rank ordered would be prioritized higher than using frequency or length alone. This work shows the deleteriousness of regulatory SVs, particularly those altering CTCF sites and provides a simple approach for functionally annotating the regulatory consequences of CNVs.

Published
2020
Full Text
View/download PDF

29. Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits.

Author

Zhang W, Voloudakis G, Rajagopal VM, Readhead B, Dudley JT, Schadt EE, Björkegren JLM, Kim Y, Fullard JF, Hoffman GE, and Roussos P

Subjects
Animals, Databases, Genetic, Datasets as Topic, Humans, Mice, Models, Genetic, Software, Epigenomics methods, Gene Expression Profiling methods, Genetic Pleiotropy, Genetic Predisposition to Disease, Quantitative Trait Loci
Abstract

Transcriptome-wide association studies integrate gene expression data with common risk variation to identify gene-trait associations. By incorporating epigenome data to estimate the functional importance of genetic variation on gene expression, we generate a small but significant improvement in the accuracy of transcriptome prediction and increase the power to detect significant expression-trait associations. Joint analysis of 14 large-scale transcriptome datasets and 58 traits identify 13,724 significant expression-trait associations that converge on biological processes and relevant phenotypes in human and mouse phenotype databases. We perform drug repurposing analysis and identify compounds that mimic, or reverse, trait-specific changes. We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that converge on shared biological pathways and elucidate distinct processes in disease etiopathogenesis. Overall, this comprehensive analysis provides insight into the specificity and convergence of gene expression on susceptibility to complex traits.

Published
2019
Full Text
View/download PDF

30. Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia.

Author

Bryois J, Garrett ME, Song L, Safi A, Giusti-Rodriguez P, Johnson GD, Shieh AW, Buil A, Fullard JF, Roussos P, Sklar P, Akbarian S, Haroutunian V, Stockmeier CA, Wray GA, White KP, Liu C, Reddy TE, Ashley-Koch A, Sullivan PF, and Crawford GE

Subjects
Aged, Aged, 80 and over, Brain physiopathology, Female, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, Sequence Analysis, DNA, Chromatin chemistry, Genome-Wide Association Study, Prefrontal Cortex metabolism, Quantitative Trait Loci, Schizophrenia genetics, Schizophrenia metabolism
Abstract

Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability. Accessible chromatin regions that overlap evolutionarily conserved regions exhibit an even higher heritability enrichment, indicating that sequence conservation can further refine functional risk variants. We identify few differences in chromatin accessibility between cases and controls, in contrast to thousands of age-related differential accessible chromatin regions. Altogether, we characterize chromatin accessibility in the human prefrontal cortex, the effect of schizophrenia and age on chromatin accessibility, and provide evidence that our dataset will allow for fine mapping of risk variants.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results