Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Authors: 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 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 Thomas H. , Bressler Jan , Lencz Todd , Deary Ian J. 
Published: May 2018

AbstractGeneral 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 (totalN = 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.