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

Authors:
Li Shuo
Li Shuo
Institute of Agricultural Remote Sensing and Information Technology
beijing, beijing | China
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 Ian J Deary

Nat Commun 2018 05 29;9(1):2098. Epub 2018 May 29.

Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.

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) 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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http://dx.doi.org/10.1038/s41467-018-04362-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974083PMC
May 2018
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