Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)
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 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 Anbu , Trompet Stella , Lee Sven J van der , 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 , Hellard Stephanie Le , 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 , 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 , Jager Philip L De , 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 , Duijn Cornelia M Van , 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: August 2017

General cognitive function is a prominent human trait associated with many important life outcomes1,2, including longevity3. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants4,5,6. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (P<5 x 10−8) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function wereSGCZ,ATXN1,MAPT,AUTS2, andP2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.