Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
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 Andreas; 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; 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; Liu, Tian; Koini, Marisa; London, Edythe; Longstreth, Will T.; Lopez, Oscar L.; Loukola, Anu; Luck, Tobias; Lundervold, Astri; Lundquist, Anders; Lyytikäinen, Leo-Pekka; Martin, Nicholas G.; Montgomery, Grant W.; Murray, Alison D.; Need, Anna C.; Noordam, Raymond; Nyberg, Lars; Ollier, William; Papenberg, Göran; 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 Søren; 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; Widén, 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; 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 Martin; 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; Deary, Ian J.
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https://doi.org/10.1038/s41467-018-04362-xAbstract
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.
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Nature ResearchJournal
Nature CommunicationsCopyright
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R.; Hormiga, Claudia M.; Horta, Bernardo L.; Houti, Leila; Howitt, Christina; Htay, Thein Thein; Htet, Aung Soe; Htike, Maung Maung Than; Hu, Yonghua; Huerta, José María; Huhtaniemi, Ilpo Tapani; Huiart, Laetitia; Petrescu, Constanta Huidumac; Huisman, Martijn; Husseini, Abdullatif; Huu, Chinh Nguyen; Huybrechts, Inge; Hwalla, Nahla; Hyska, Jolanda; Iacoviello, Licia; Iakupova, Ellina M.; Ibarluzea, Jesús M.; Ibrahim, Mohsen M.; Wong, Norazizah Ibrahim; Ikram, M. Arfan; Iñiguez, Carmen; Iotova, Violeta; Irazola, Vilma E.; Ishida, Takafumi; Isiguzo, Godsent C.; Islam, Muhammad; Islam, Sheikh Mohammed Shariful; Islek, Duygu; Ivanova-Pandourska, Ivaila Y.; Iwasaki, Masanori; Jääskeläinen, Tuija; Jackson, Rod T.; Jacobs, Jeremy M.; Jadoul, Michel; Jafar, Tazeen; Jallow, Bakary; James, Kenneth; Jamil, Kazi M.; Jamrozik, Konrad; Jansson, Anna; Janszky, Imre; Janus, Edward; Jarani, Juel; Jarvelin, Marjo-Riitta; Jasienska, Grazyna; Jelaković, Ana; Jelaković, Bojan; Jennings, Garry; Jiang, Chao Qiang; Jimenez, Ramon O.; Jöckel, Karl-Heinz; Joffres, Michel; Jokelainen, Jari J.; Jonas, Jost B.; Jonnagaddala, Jitendra; Jørgensen, Torben; Joshi, Pradeep; Josipović, Josipa; Joukar, Farahnaz; Jóźwiak, Jacek J.; Judge, Debra S.; Juolevi, Anne; Jurak, Gregor; Simina, Iulia Jurca; Juresa, Vesna; Kaaks, Rudolf; Kaducu, Felix O.; Kafatos, Anthony; Kaj, Mónika; Kajantie, Eero Olavi; Kakutia, Natia; Kállayová, Daniela; Kalmatayeva, Zhanna; Kalter-Leibovici, Ofra; Kameli, Yves; Kampmann, Freja B.; Kanala, Kodanda R.; Kannan, Srinivasan; Kapantais, Efthymios; Karaglani, Eva; Karakosta, Argyro; Kårhus, Line L.; Karki, Khem B.; Katchunga, Philippe B.; Katibeh, Marzieh; Katz, Joanne; Katzmarzyk, Peter T.; Kauhanen, Jussi; Kaur, Prabhdeep; Kavousi, Maryam; Kazakbaeva, Gyulli M.; Kaze, François F.; Ke, Calvin; Keil, Ulrich; Boker, Lital Keinan; Keinänen-Kiukaanniemi, Sirkka; Kelishadi, Roya; Kelleher, Cecily; Kemper, Han C. 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Fernanda; Lin, Hsien-Ho; Lin, Xu; Lin, Yi-Ting; Lind, Lars; Lingam, Vijaya; Linkohr, Birgit; Linneberg, Allan; Lissner, Lauren; Litwin, Mieczyslaw; Liu, Jing; Liu, Lijuan; Lo, Wei-Cheng; Loit, Helle-Mai; Long, Khuong Quynh; Abril, Guadalupe Longo; Lopes, Luis; Lopes, Marcus V. V.; Lopes, Oscar; Lopez-Garcia, Esther; Lopez, Tania; Lotufo, Paulo A.; Lozano, José Eugenio; Lukrafka, Janice L.; Luksiene, Dalia; Lundqvist, Annamari; Lunet, Nuno; Lunogelo, Charles; Lustigová, Michala; Łuszczki, Edyta; M’Buyamba-Kabangu, Jean-René; Ma, Guansheng; Ma, Xu; Machado-Coelho, George L. 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M.; Menzano, Maria Teresa; Meshram, Indrapal I.; Meto, Diane T.; Mi, Jie; Michaelsen, Kim F.; Michels, Nathalie; Mikkel, Kairit; Miłkowska, Karolina; Miller, Jody C.; Milushkina, Olga; Minderico, Cláudia S.; Mini, G.K.; Miquel, Juan Francisco; Miranda, J. Jaime; Mirjalili, Mohammad Reza; Mirkopoulou, Daphne; Mirrakhimov, Erkin; Mišigoj-Duraković, Marjeta; Mistretta, Antonio; Mocanu, Veronica; Modesti, Pietro A.; Moghaddam, Sahar Saeedi; Mohajer, Bahram; Mohamed, Mostafa K.; Mohamed, Shukri F.; Mohammad, Kazem; Mohammadi, Mohammad Reza; Mohammadi, Zahra; Mohammadifard, Noushin; Mohammadpourhodki, Reza; Mohan, Viswanathan; Mohanna, Salim; Yusoff, Muhammad Fadhli Mohd; Mohebbi, Iraj; Mohebi, Farnam; Moitry, Marie; Møllehave, Line T.; Møller, Niels C.; Molnár, Dénes; Momenan, Amirabbas; Mondo, Charles K.; Montenegro Mendoza, Roger A.; Monterrubio-Flores, Eric; Monyeki, Kotsedi Daniel K.; Moon, Jin Soo; Moosazadeh, Mahmood; Mopa, Hermine T.; Moradpour, Farhad; Moreira, Leila B.; Morejon, Alain; Moreno, Luis A.; Morey, Francis; Morgan, Karen; Morin, Suzanne N.; Mortensen, Erik Lykke; Moschonis, George; Moslem, Alireza; Mossakowska, Malgorzata; Mostafa, Aya; Mostafavi, Seyed-Ali; Mota-Pinto, Anabela; Mota, Jorge; Motlagh, Mohammad Esmaeel; Motta, Jorge; Moura-dos-Santos, Marcos André; Movsesyan, Yeva; Msyamboza, Kelias P.; Mu, Thet Thet; Muc, Magdalena; Muca, Florian; Mugoša, Boban; Muiesan, Maria L.; Müller-Nurasyid, Martina; Münzel, Thomas; Mursu, Jaakko; Murtagh, Elaine M.; Musa, Kamarul Imran; Milanović, Sanja Musić; Musil, Vera; Musinguzi, Geofrey; Muyer, Muel Telo M. 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C.; Ramires, Virgílio V.; Ramke, Jacqueline; Ramos, Elisabete; Ramos, Rafel; Rampal, Lekhraj; Rampal, Sanjay; Rangelova, Lalka S.; Rarra, Vayia; Rascon-Pacheco, Ramon A.; Rech, Cassiano Ricardo; Redon, Josep; Reganit, Paul Ferdinand M.; Regecová, Valéria; Renner, Jane D. 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Goya; Wareham, Nicholas; Weber, Adelheid; Webster-Kerr, Karen; Wedderkopp, Niels; Weghuber, Daniel; Wei, Wenbin; Weres, Aneta; Werner, Bo; Westbury, Leo D.; Whincup, Peter H.; Wickramasinghe, Kremlin; Widhalm, Kurt; Widyahening, Indah S.; Więcek, Andrzej; Wild, Philipp S.; Wilks, Rainford J.; Willeit, Johann; Willeit, Peter; Williams, Julianne; Wilsgaard, Tom; Wojciech, Rusek; Wojtyniak, Bogdan; Wolf, Kathrin; Wong-McClure, Roy A.; Wong, Andrew; Wong, Emily B.; Wong, Jyh Eiin; Wong, Tien Yin; Woo, Jean; Woodward, Mark; Wu, Frederick C.; Wu, Hon-Yen; Wu, Jianfeng; Wu, Li Juan; Wu, Shouling; Wyszyńska, Justyna; Xu, Haiquan; Xu, Liang; Yaacob, Nor Azwany; Yamborisut, Uruwan; Yan, Weili; Yang, Ling; Yang, Xiaoguang; Yang, Yang; Yardim, Nazan; Yasuharu, Tabara; García, Martha Yépez; Yiallouros, Panayiotis K.; Yngve, Agneta; Yoosefi, Moein; Yoshihara, Akihiro; You, Qi Sheng; You, San-Lin; Younger-Coleman, Novie O.; Yu, Yu-Ling; Yu, Yunjiang; Yusof, Safiah Md; Yusoff, Ahmad Faudzi; Zaccagni, Luciana; Zafiropulos, Vassilis; Zainuddin, Ahmad A.; Zakavi, Seyed Rasoul; Zamani, Farhad; Zambon, Sabina; Zampelas, Antonis; Zamrazilová, Hana; Zapata, Maria Elisa; Zargar, Abdul Hamid; Zaw, Ko Ko; Zayed, Ayman A.; Zdrojewski, Tomasz; Żegleń, Magdalena; Zejglicova, Kristyna; Vrkic, Tajana Zeljkovic; Zeng, Yi; Zhang, Luxia; Zhang, Zhen-Yu; Zhao, Dong; Zhao, Ming-Hui; Zhao, Wenhua; Zhecheva, Yanitsa V.; Zhen, Shiqi; Zheng, Wei; Zheng, Yingfeng; Zholdin, Bekbolat; Zhou, Maigeng; Zhu, Dan; Zins, Marie; Zitt, Emanuel; Zocalo, Yanina; Zoghlami, Nada; Cisneros, Julio Zuñiga; Zuziak, Monika; Bhutta, Zulfiqar A.; Black, Robert E.; Ezzati, Majid (Journal article; Peer reviewed, 2023)Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1,2,3,4,5,6. Here we used data from 2,325 population-based studies, with measurements of height and weight from ... -
PDBe-KB: collaboratively defining the biological context of structural data
Varadi, Mihaly; Anyango, Stephen; Armstrong, David; Berrisford, John; Choudhary, Preeti; Deshpande, Mandar; Nadzirin, Nurul; Nair, Sreenath S.; Pravda, Lukas; Tanweer, Ahsan; Al-Lazikani, Bissan; Andreini, Claudia; Barton, Geoffrey J.; Bednar, David; Berka, Karel; Blundell, Tom; Brock, Kelly P.; Carazo, Jose Maria; Damborsky, Jiri; David, Alessia; Dey, Sucharita; Dunbrack, Roland; Recio, Juan Fernandez; Fraternali, Franca; Gibson, Toby; Helmer-Citterich, Manuela; Hoksza, David; Hopf, Thomas; Jakubec, David; Kannan, Natarajan; Krivak, Radoslav; Kumar, Manjeet; Levy, Emmanuel D.; London, Nir; Macias, Jose Ramon; Srivatsan, Madhusudhan M.; Marks, Debora S.; Martens, Lennart; McGowan, Stuart A.; McGreig, Jake E.; Modi, Vivek; Parra, R. Gonzalo; Pepe, Gerardo; Piovesan, Damiano; Prilusky, Jaime; Putignano, Valeria; Radusky, Leandro G.; Ramasamy, Pathmanaban; Rausch, Atilio O.; Reuter, Nathalie; Rodriguez, Luis A.; Rollins, Nathan J.; Rosato, Antonio; Rubach, Paweł; Serrano, Luis; Singh, Gulzar; Skoda, Petr; Sorzano, Carlos Oscar S.; Stourac, Jan; Sulkowska, Joanna I.; Svobodova, Radka; Tichshenko, Natalia; Tosatto, Silvio C.E.; Vranken, Wim; Wass, Mark N.; Xue, Dandan; Zaidman, Daniel; Thornton, Janet; Sternberg, Michael; Orengo, Christine; Velankar, Sameer (Journal article; Peer reviewed, 2022)The Protein Data Bank in Europe – Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or ...