10 results on '"Hariri, A. R."'
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2. Hariri_Supplemental_Material_rev – Supplemental material for What Is the Test-Retest Reliability of Common Task-Functional MRI Measures? New Empirical Evidence and a Meta-Analysis
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Elliott, Maxwell L., Knodt, Annchen R., Ireland, David, Meriwether L. Morris, Poulton, Richie, Ramrakha, Sandhya, Sison, Maria L., Moffitt, Terrie E., Caspi, Avshalom, and Hariri, Ahmad R.
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FOS: Psychology ,FOS: Clinical medicine ,170199 Psychology not elsewhere classified ,110319 Psychiatry (incl. Psychotherapy) ,110904 Neurology and Neuromuscular Diseases ,Neuroscience - Abstract
Supplemental material, Hariri_Supplemental_Material_rev for What Is the Test-Retest Reliability of Common Task-Functional MRI Measures? New Empirical Evidence and a Meta-Analysis by Maxwell L. Elliott, Annchen R. Knodt, David Ireland, Meriwether L. Morris, Richie Poulton, Sandhya Ramrakha, Maria L. Sison, Terrie E. Moffitt, Avshalom Caspi and Ahmad R. Hariri in Psychological Science
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- 2020
- Full Text
- View/download PDF
3. A role for the CD38 rs3796863 polymorphism in alcohol and monetary reward: evidence from CD38 knockout mice and alcohol self-administration, [11C]-raclopride binding, and functional MRI in humans
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Lee, Mary R., Shin, Jung H., Deschaine, Sara, Daurio, Allison M., Stangl, Bethany L., Yan, Jia, Ramchandani, Vijay A., Schwandt, Melanie L., Grodin, Erica N., Momenan, Reza, Corral-Frias, Nadia S., Hariri, Ahmad R., Bogdan, Ryan, Alvarez, Veronica A., and Leggio, Lorenzo
- Abstract
Background: Cluster of differentiation 38 (CD38) is a transmembrane protein expressed in dopaminergic reward pathways in the brain, including the nucleus accumbens (NAc). The GG genotype of a common single nucleotide polymorphism (SNP) within CD38, rs3796863, is associated with increased social reward. Objective: Examine whether CD38 rs3796863 and Cd38 knockout (KO) are associated with reward-related neural and behavioral phenotypes. Methods: Data from four independent human studies were used to test whether rs3796863 genotype is associated with: (1) intravenous alcohol self-administration (n = 64, 30 females), (2) alcohol-stimulated dopamine (DA) release measured using 11C-raclopride positron emission tomography (n = 22 men), (3) ventral striatum (VS) response to positive feedback measured using a card guessing functional magnetic resonance imaging (fMRI) paradigm (n = 531, 276 females), and (4) resting state functional connectivity (rsfc) of the VS (n = 51, 26 females). In a fifth study, we used a mouse model to examine whether cd38 knockout influences stimulated DA release in the NAc core and dorsal striatum using fast-scanning cyclic voltammetry. Results: Relative to T allele carriers, G homozygotes at rs3796863 within CD38 were characterized by greater alcohol self-administration, alcohol-stimulated dopamine release, VS response to positive feedback, and rsfc between the VS and anterior cingulate cortex. High-frequency stimulation reduced DA release among Cd38 KO mice had reduced dopamine release in the NAc. Conclusion: Converging evidence suggests that CD38 rs3796863 genotype may increase DA-related reward response and alcohol consumption.
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- 2020
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- View/download PDF
4. Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium
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Hofer, Edith, Roshchupkin, Gennady V., Adams, Hieab H. H., Knol, Maria J., Lin, Honghuang, Li, Shuo, Zare, Habil, Ahmad, Shahzad, Armstrong, Nicola J., Satizabal, Claudia L., Bernard, Manon, Bis, Joshua C., Gillespie, Nathan A., Luciano, Michelle, Mishra, Aniket, Scholz, Markus, Teumer, Alexander, Xia, Rui, Jian, Xueqiu, Mosley, Thomas H., Saba, Yasaman, Pirpamer, Lukas, Seiler, Stephan, Becker, James T., Carmichael, Owen, Rotter, Jerome I., Psaty, Bruce M., Lopez, Oscar L., Amin, Najaf, van der Lee, Sven J., Yang, Qiong, Himali, Jayandra J., Maillard, Pauline, Beiser, Alexa S., DeCarli, Charles, Karama, Sherif, Lewis, Lindsay, Harris, Mat, Bastin, Mark E., Deary, Ian J., Witte, A.Veronica, Beyer, Frauke, Loeffler, Markus, Mather, Karen A., Schofield, Peter R., Thalamuthu, Anbupalam, Kwok, John B., Wright, Margaret J., Ames, David, Trollor, Julian, Jiang, Jiyang, Brodaty, Henry, Wen, Wei, Vernooij, Meike W, Hofman, Albert, Uitterlinden, André G., Niessen, Wiro J., Wittfeld, Katharina, Bülow, Robin, Völker, Uwe, Pausova, Zdenka, Pike, G. Bruce, Maingault, Sophie, Crivello, Fabrice, Tzourio, Christophe, Amouye, Philippe, Mazoyer, Bernard, Neale, Michael C., Franz, Carol E., Lyons, Michael J., Panizzon, Matthew S., Andreassen, Ole A., Dale, Anders M., Logue, Mark, Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Stein, Jason L., Thompson, Paul M., Medland, Sarah E., Ching Christopher, R.K., McMahon Mary Agnes, B., Shatokhina, Natalia, Zsembik, Leo C.P., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A.A., Alnæs, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Ashley-Koch, Allison, Brouwer, Rachel M., Buimer, Elizabeth E.L., Bürger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dalvie, Shareefa, de Araujo, Tânia K., de Zubicaray, Greig I., de Zwarte, Sonja M.C., Braber, Anouk den, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Krämer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C.V., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M., Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Pütz, Benno, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Ronny, Redlich, Reinbold, Céline S., Repple, Jonathan, Richard, Geneviève, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E., Sprooten, Emma, Strike, Lachlan T., Tansey, Katherine E., Thomopoulos, Sophia I., Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza Ludovica, der Meer, Dennis van, van Donkelaar, Marjolein M.J., Eijk, Liza van, van Erp, Theo G.M., van Haren, Neeltje E.M., Rooij, Daan van, van Tol, Marie-José, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wolf, Christiane, Wolfers, Thomas, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zhu, Alyssa H., Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Häusler, Alexander N., Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack Jr., Clifford R., Jang, MiHyun, Jansen, Andreas, Kolskår, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mattay, Venkata S., Matthews, Sarah, Van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Nöthen, Markus M., O’Leary, Daniel S., Opel, Nils, Paillère Martinot, Marie-Laure, Preda, Adrian, Quinlan, Erin B., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Torres, Fábio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Alvim, Marina K.M., Anderson, Tim J., Arias-Vasquez, Alejandro, Baune, Bernhard T., Blangero, John, Boomsma, Dorret I., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bustillo, Juan R., Cahn, Wiepke, Calhoun, Vince, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L., Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dannlowski, Udo, de Geus, Eco J.C., Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E., Flor, Herta, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Glahn, David C., Gollub, Randy L., Grabe, Hans J., Gruber, Oliver, Håberg, Asta K., Hariri, Ahmad R., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Hillegers, Manon H.J., Hoekstra, Pieter J., Holmes, Avram J., Hong, L. Elliot, Hopkins, William D., Hulshoff Pol, Hilleke E., Jernigan, Terry L., Jönsson, Erik G., Kahn, René S., Kennedy, Martin A., Kircher, Tilo T.J., Kochunov, Peter, Kwok, John B.J., Hellard, Stephanie Le, Martin, Nicholas G., Martinot, Jean - Luc, McDonald, Colm, McMahon, Katie L., Meyer-Lindenberg, Andreas, Morey, Rajendra A., Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A., Paus, Tomáš, Penninx, Brenda W.J.H., Polderman, Tinca J.C., Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L., Rowland, Laura M., Sachdev, Perminder S., Sämann, Philipp G., Schumann, Gunter, Sim, Kang, Sisodiya, Sanjay M., Smoller, Jordan W., Sommer, Iris E., Pourcain, Beate St, Stein, Dan J., Toga, Arthur W., Trollor, Julian N., Van der Wee, Nic J.A., Ent, Dennis van’t, Völzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R., Zhou, Juan, Kremen, William S., Villringer, Arno, Duijn, Cornelia M. van, Jörgen Grabe, Hans, Longstreth Jr, William T., Fornage, Myriam, Paus, Tomas, Debette, Stephanie, Ikram, M. Arfan, Schmidt, Helena, Schmidt, Reinhold, Seshadri, Sudha, and ENIGMA consortium
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0303 health sciences ,biology ,Genetic heterogeneity ,Cognition ,Hindbrain ,Disease ,Heritability ,Biobank ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Evolutionary biology ,Cortex (anatomy) ,biology.protein ,medicine ,Sonic hedgehog ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
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- 2018
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5. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
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Savage, Jeanne E, Jansen, Philip R, Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, de Leeuw, Christiaan A, Nagel, Mats, Awasthi, Swapnil, Barr, Peter B, Coleman, Jonathan RI, Grasby, Katrina L, Hammerschlag, Anke R, Kaminski, Jakob A, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A, Trampush, Joey W, Young, Hannah, Zabaneh, Delilah, Hägg, Sara, Hansell, Narelle K, Karlsson, Ida K, Linnarsson, Sten, Montgomery, Grant W, Muñoz-Manchado, Ana B, Quinlan, Erin B, Schumann, Gunter, Skene, Nathan G, Webb, Bradley T, White, Tonya, Arking, Dan E, Avramopoulos, Dimitrios, Bilder, Robert M, Bitsios, Panos, Burdick, Katherine E, Cannon, Tyrone D, Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T, Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J, DeRosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G, Espeseth, Thomas, Freimer, Nelson A, Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C, Hariri, Ahmad R, Hatzimanolis, Alex, Keller, Matthew C, Knowles, Emma, Koltai, Deborah, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C, London, Edythe, Lundervold, Astri J, Malhotra, Anil K, Melle, Ingrid, Morris, Derek, Need, Anna C, Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A, Räikkönen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W, Scult, Matthew A, Smeland, Olav B, Smyrnis, Nikolaos, Starr, John M, Steen, Vidar M, Stefanis, Nikos C, Straub, Richard E, Sundet, Kjetil, Tiemeier, Henning, Voineskos, Aristotle N, Weinberger, Daniel R, Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A, Breen, Gerome, and Christiansen, Lene
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Male ,Adolescent ,1.1 Normal biological development and functioning ,Intelligence ,Quantitative Trait Loci ,Medical and Health Sciences ,Underpinning research ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Genetic Predisposition to Disease ,Aetiology ,Polymorphism ,Human Genome ,Neurosciences ,Brain ,Single Nucleotide ,Middle Aged ,Biological Sciences ,Brain Disorders ,Mental Health ,Neurological ,Female ,Biotechnology ,Genome-Wide Association Study ,Developmental Biology - Abstract
Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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- 2018
6. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
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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 CM, Okely, Judith A, Ahola-Olli, Ari V, Barnes, Catriona LK, 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 LR, 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, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, 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 HH, 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, Rujescu, Dan, 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, Thomas H, Bressler, Jan, Lencz, Todd, and Deary, Ian J
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quantitative trait ,cognitive neuroscience ,genetics of the nervous system ,genome-wide association studies ,3. Good health - Abstract
General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
7. GWAS meta-analysis (N=279,930) identifies new genes and functional links to general cognitive ability
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Savage, Jeanne E., Jansen, Philip R., Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, Leeuw, Christiaan A., Nagel, Mats, Awasthi, Swapnil, Barr, Peter B., Coleman, Jonathan R. I., Grasby, Katrina L., Hammerschlag, Anke R., Kaminski, Jakob, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A., Trampush, Joey W., Young, Hannah, Zabaneh, Delilah, Hagg, Sara, Hansell, Narelle K., Karlsson, Ida K., Linnarsson, Sten, Montgomery, Grant W., Munoz-Manchado, Ana B., Quinlan, Erin B., Schumann, Gunter, Skene, Nathan, Webb, Bradley T., White, Tonya, Arking, Dan E., Attix, Deborah K., Avramopoulos, Dimitrios, Bilder, Robert M., Bitsios, Panos, Burdick, Katherine E., Cannon, Tyrone D., Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T., Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J., Derosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G., Espeseth, Thomas, Freimer, Nelson A., Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C., Hariri, Ahmad R., Hatzimanolis, Alex, Keller, Matthew C., Knowles, Emma, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C., London, Edythe, Lundervold, Astri J., Malhotra, Anil K., Melle, Ingrid, Morris, Derek, Need, Anna C., Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A., Raikkonen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W., Scult, Matthew A., Smeland, Olav B., Smyrnis, Nikolaos, Starr, John M., Steen, Vidar M., Stefanis, Nikos C., Straub, Richard E., Sundet, Kjetil, Voineskos, Aristotle N., Weinberger, Daniel R., Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A., Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M., Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M. Arfan, Kendler, Kenneth S., Martin, Nicholas G., Medland, Sarah E., Pedersen, Nancy L., Plomin, Robert, Polderman, Tinca J. C., Ripke, Stephan, Sluis, Sophie, Sullivan, Patrick F., Tiemeier, Henning, Vrieze, Scott I., Margaret Wright, and Posthuma, Danielle
8. Exploring the mind: Integrating questionnaires and fMRI
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Salazar, E., Bogdan, R., Gorka, A., Hariri, A. R., and Lawrence Carin
9. A Novel Experimental Method for Measuring Proactive and Reactive Responses to Threat and an Examination of Their Personality and Neural Correlates
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Gorka, Adam and Hariri, Ahmad R
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Individual Differences ,fMRI ,Neurosciences ,Active Avoidance ,Psychobiology ,Threat ,Personality - Abstract
The goal of this dissertation is to characterize goal directed proactive behavioral responses to threat as well as reactive responses to threat exposure, and to identify the neural and personality correlates of individual differences in these responses. Three specific studies are reported wherein participants completed a novel shock avoidance paradigm while concurrent measures of behavioral, muscular, and sympathetic autonomic activity were collected; self-report was used to measure mood and trait personality; and blood oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI) was used to measure individual differences in threat-related amygdala reactivity and intrinsic connectivity within the corticolimbic circuit.Results from Study 1 demonstrate that during threat exposure, participants exhibit increased avoidance behavior, faster reaction times, and increased muscular and sympathetic activity. Moreover, results demonstrate that two broad patterns characterize individual differences in how participants respond during avoidance: 1) a generalized tendency to exhibit magnified threat responses across domains; and 2) a tendency to respond either with proactive behavioral responses or reactive autonomic responses. Heightened state anxiety during the shock avoidance paradigm, and increased trait anxiety were both associated with the generalized tendency to exhibit magnified threat responses. However, gender moderated the relationship between trait anxiety and generalized increases in threat responses during avoidance, such that only male participants exhibited a positive relationship between these two factors. Study 2 demonstrates that intrinsic connectivity between the dorsomedial prefrontal cortex and centromedial region of the amygdala prospectively predicts whether participants will respond proactively or reactively during active avoidance. Finally, Study 3 provides evidence that responses to threat-related facial expressions within the centromedial region of the amygdala are associated with more reactive and less proactive responses during avoidance. These results demonstrate that patterns observed in animal models of avoidance, specifically the competition between proactive and reactive responses to threat cues, extend to human participants. Moreover, our results suggest that while anxious mood during performance and heightened trait anxiety are associated with a generalized facilitation of threat responses across domains, measures of neural circuit function within the corticolimbic system predict whether individuals will exhibit increased proactive or reactive responses during active avoidance. In addition to facilitating the search for the neural processes underlying how the brain responds dynamically to threat, these results have the potential to aide researchers in characterizing the symptoms and neural processes underlying anxiety disorders.
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- 2015
10. Imputation of Microsatellite Markers With Tag SNPs
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Knodt, Annchen and Hariri, Ahmad R
- Subjects
Bioinformatics - Abstract
Of the two most common forms of genetic variation in the human genome, Single Nucleotide Polymorphisms (SNPs) and Variable Number Tandem Repeat Polymorphisms (VNTRs), SNPs are much more easily and inexpensively assayed in a high-throughput manner. For this reason, we seek to explore methods that can allow us to use the more readily available SNP genotype information to infer VNTR genotypes in nearby genomic regions. We focus in particular on imputing a VNTR polymorphism, 5-HTTLPR, in the promoter region of the serotonin transporter gene in a small sample of individuals from an ongoing neuroimaging genetics study, a portion of whom have both manual 5-HTTLPR genotypes and genome wide SNP data. We investigate four imputation methods: Tagger, Vertex Discriminant Analysis (VDA), IMPUTE2, and BEAGLE. We achieve an accuracy of 93% with VDA in our subsample of Caucasians with manual 5-HTTLPR genotypes. Further, we find that for the entire Caucasian subsample without manual genotypes, a majority of the imputation methods tested make the same 5-HTTLPR genotype call.
- Published
- 2012
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