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

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. Kamran 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; 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

doi:10.1038/s41467-018-04362-x

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

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 DjurovicThomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Kamran 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, 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^*

^*Corresponding author for this work

339 Citations (Scopus)

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.

Original language	English
Article number	2098
Journal	Nature Communications
Volume	9
Issue number	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-018-04362-x
Publication status	Published - 01.12.2018

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Cite this

Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns-Ritchie, C., Liewald, D. C. M., Okely, J. A., Ahola-Olli, A. V., Barnes, C. L. K., Bertram, L., Bis, J. C., Burdick, K. E., Christoforou, A., Derosse, P., ... Deary, I. J. (2018). Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nature Communications, 9(1), Article 2098. https://doi.org/10.1038/s41467-018-04362-x

@article{2d61c26fc2704e87893be37590d54ced,

title = "Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function",

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.",

author = "Gail Davies and Max Lam and Harris, {Sarah E.} and Trampush, {Joey W.} and Michelle Luciano and Hill, {W. David} and Hagenaars, {Saskia P.} and Ritchie, {Stuart J.} and Marioni, {Riccardo E.} and Chloe Fawns-Ritchie and Liewald, {David C.M.} and Okely, {Judith A.} and Ahola-Olli, {Ari V.} and Barnes, {Catriona L.K.} and Lars Bertram and Bis, {Joshua C.} and Burdick, {Katherine E.} and Andrea Christoforou and Pamela Derosse and Srdjan Djurovic and Thomas Espeseth and Stella Giakoumaki and Sudheer Giddaluru and Gustavson, {Daniel E.} and Caroline Hayward and Edith Hofer and Ikram, {M. Kamran} and Robert Karlsson and Emma Knowles and Jari Lahti and Markus Leber and Shuo Li and Mather, {Karen A.} and Ingrid Melle and Derek Morris and Christopher Oldmeadow and Teemu Palviainen and Antony Payton and Raha Pazoki and Katja Petrovic and Reynolds, {Chandra A.} and Muralidharan Sargurupremraj and Markus Scholz and Smith, {Jennifer A.} and Smith, {Albert V.} and Natalie Terzikhan and Anbupalam Thalamuthu and Stella Trompet and {Van Der Lee}, {Sven J.} and Ware, {Erin B.} and Windham, {B. Gwen} and Wright, {Margaret J.} and Jingyun Yang and Jin Yu and David Ames and Najaf Amin and Philippe Amouyel and Andreassen, {Ole A.} and Armstrong, {Nicola J.} and Assareh, {Amelia A.} and Attia, {John R.} and Deborah Attix and Dimitrios Avramopoulos and Bennett, {David A.} and B{\"o}hmer, {Anne C.} and Boyle, {Patricia A.} and Henry Brodaty and Harry Campbell and Cannon, {Tyrone D.} and Cirulli, {Elizabeth T.} and Eliza Congdon and Conley, {Emily Drabant} and Janie Corley and Cox, {Simon R.} and Dale, {Anders M.} and Abbas Dehghan and Danielle Dick and Dwight Dickinson and Eriksson, {Johan G.} and Evangelos Evangelou and Faul, {Jessica D.} and Ian Ford and Freimer, {Nelson A.} and He Gao and Ina Giegling and Gillespie, {Nathan A.} and Gordon, {Scott D.} and Gottesman, {Rebecca F.} and Griswold, {Michael E.} and Vilmundur Gudnason and Harris, {Tamara B.} and Hartmann, {Annette M.} and Alex Hatzimanolis and Gerardo Heiss and Holliday, {Elizabeth G.} and Joshi, {Peter K.} and Mika K{\"a}h{\"o}nen and Kardia, {Sharon L.R.} and Ida Karlsson and Luca Kleineidam and Knopman, {David S.} and Kochan, {Nicole A.} and Bettina Konte and Kwok, {John B.} and {Le Hellard}, Stephanie and Teresa Lee and Terho Lehtim{\"a}ki and Li, {Shu Chen} and Tian Liu and Marisa Koini and Edythe London and Longstreth, {Will T.} and Lopez, {Oscar L.} and Anu Loukola and Tobias Luck and Lundervold, {Astri J.} and Anders Lundquist and Lyytik{\"a}inen, {Leo Pekka} and Martin, {Nicholas G.} and Montgomery, {Grant W.} and Murray, {Alison D.} and Need, {Anna C.} and Raymond Noordam and Lars Nyberg and William Ollier and Goran Papenberg and Alison Pattie and Ozren Polasek and Poldrack, {Russell A.} and Psaty, {Bruce M.} and Simone Reppermund and Riedel-Heller, {Steffi G.} and Rose, {Richard J.} and Rotter, {Jerome I.} and Panos Roussos and Rovio, {Suvi P.} and Yasaman Saba and Sabb, {Fred W.} and Sachdev, {Perminder S.} and Satizabal, {Claudia L.} and Matthias Schmid and Scott, {Rodney J.} and Scult, {Matthew A.} and Jeannette Simino and Slagboom, {P. Eline} and Nikolaos Smyrnis and A{\"i}cha Soumar{\'e} and Stefanis, {Nikos C.} and Stott, {David J.} and Straub, {Richard E.} and Kjetil Sundet and Taylor, {Adele M.} and Taylor, {Kent D.} and Ioanna Tzoulaki and Christophe Tzourio and Andr{\'e} Uitterlinden and Veronique Vitart and Voineskos, {Aristotle N.} and Jaakko Kaprio and Michael Wagner and Holger Wagner and Leonie Weinhold and Wen, {K. Hoyan} and Elisabeth Widen and Qiong Yang and Wei Zhao and Adams, {Hieab H.H.} and Arking, {Dan E.} and Bilder, {Robert M.} and Panos Bitsios and Eric Boerwinkle and Ornit Chiba-Falek and Aiden Corvin and {De Jager}, {Philip L.} and St{\'e}phanie Debette and Gary Donohoe and Paul Elliott and Fitzpatrick, {Annette L.} and Michael Gill and Glahn, {David C.} and Sara H{\"a}gg and Hansell, {Narelle K.} and Hariri, {Ahmad R.} and Ikram, {M. Kamran} and Jukema, {J. Wouter} and Eero Vuoksimaa and Keller, {Matthew C.} and Kremen, {William S.} and Lenore Launer and Ulman Lindenberger and Aarno Palotie and Pedersen, {Nancy L.} and Neil Pendleton and Porteous, {David J.} and Katri R{\"a}ikk{\"o}nen and Raitakari, {Olli T.} and Alfredo Ramirez and Ivar Reinvang and Igor Rudan and Dan Rujescu and Reinhold Schmidt and Helena Schmidt and Schofield, {Peter W.} and Schofield, {Peter R.} and Starr, {John M.} and Steen, {Vidar M.} and Trollor, {Julian N.} and Turner, {Steven T.} and {Van Duijn}, {Cornelia M.} and Arno Villringer and Weinberger, {Daniel R.} and Weir, {David R.} and Wilson, {James F.} and Anil Malhotra and McIntosh, {Andrew M.} and Gale, {Catharine R.} and Sudha Seshadri and Mosley, {Thomas H.} and Jan Bressler and Todd Lencz and Deary, {Ian J.}",

note = "Funding Information: This research was conducted in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, funded by the Biotechnology and Biological Sciences Research Council and Medical Research Council (MR/K026992/1). This research was conducted using the UK Biobank Resource (Application Nos. 10279 and 4844). The Neurology Working Group within the Cohorts for Heart and Aging Research in Genomic Epidemiology is partly supported by grants from the National Institute on Aging (R01 AG033193, U01 AG049505 and U01 AG052409). Cohort-specific acknowledgements are in Supplementary Note 3. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-04362-x",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "1751-8628",

number = "1",

}

Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, Derosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MK, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, Van Der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, Brodaty, H, Campbell, H, Cannon, TD, Cirulli, ET, Congdon, E, Conley, ED, Corley, J, Cox, SR, Dale, AM, Dehghan, A, Dick, D, Dickinson, D, Eriksson, JG, Evangelou, E, Faul, JD, Ford, I, Freimer, NA, Gao, H, Giegling, I, Gillespie, NA, Gordon, SD, Gottesman, RF, Griswold, ME, Gudnason, V, Harris, TB, Hartmann, AM, Hatzimanolis, A, Heiss, G, Holliday, EG, Joshi, PK, Kähönen, M, Kardia, SLR, Karlsson, I, Kleineidam, L, Knopman, DS, Kochan, NA, Konte, B, Kwok, JB, Le Hellard, S, Lee, T, Lehtimäki, T, Li, SC, Liu, T, Koini, M, London, E, Longstreth, WT, Lopez, OL, Loukola, A, Luck, T, Lundervold, AJ, Lundquist, A, Lyytikäinen, LP, Martin, NG, Montgomery, GW, Murray, AD, Need, AC, Noordam, R, Nyberg, L, Ollier, W, Papenberg, G, Pattie, A, Polasek, O, Poldrack, RA, Psaty, BM, Reppermund, S, Riedel-Heller, SG, Rose, RJ, Rotter, JI, Roussos, P, Rovio, SP, Saba, Y, Sabb, FW, Sachdev, PS, Satizabal, CL, Schmid, M, Scott, RJ, Scult, MA, Simino, J, Slagboom, PE, Smyrnis, N, Soumaré, A, Stefanis, NC, Stott, DJ, Straub, RE, Sundet, K, Taylor, AM, Taylor, KD, Tzoulaki, I, Tzourio, C, Uitterlinden, A, Vitart, V, Voineskos, AN, Kaprio, J, Wagner, M, Wagner, H, Weinhold, L, Wen, KH, Widen, E, Yang, Q, Zhao, W, Adams, HHH, Arking, DE, Bilder, RM, Bitsios, P, Boerwinkle, E, Chiba-Falek, O, Corvin, A, De Jager, PL, Debette, S, Donohoe, G, Elliott, P, Fitzpatrick, AL, Gill, M, Glahn, DC, Hägg, S, Hansell, NK, Hariri, AR, Ikram, MK, Jukema, JW, Vuoksimaa, E, Keller, MC, Kremen, WS, Launer, L, Lindenberger, U, Palotie, A, Pedersen, NL, Pendleton, N, Porteous, DJ, Räikkönen, K, Raitakari, OT, Ramirez, A, Reinvang, I, Rudan, I, Rujescu, D, Schmidt, R, Schmidt, H, Schofield, PW, Schofield, PR, Starr, JM, Steen, VM, Trollor, JN, Turner, ST, Van Duijn, CM, Villringer, A, Weinberger, DR, Weir, DR, Wilson, JF, Malhotra, A, McIntosh, AM, Gale, CR, Seshadri, S, Mosley, TH, Bressler, J, Lencz, T & Deary, IJ 2018, 'Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function', Nature Communications, vol. 9, no. 1, 2098. https://doi.org/10.1038/s41467-018-04362-x

TY - JOUR

T1 - Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

AU - Davies, Gail

AU - Lam, Max

AU - Harris, Sarah E.

AU - Trampush, Joey W.

AU - Luciano, Michelle

AU - Hill, W. David

AU - Hagenaars, Saskia P.

AU - Ritchie, Stuart J.

AU - Marioni, Riccardo E.

AU - Fawns-Ritchie, Chloe

AU - Liewald, David C.M.

AU - Okely, Judith A.

AU - Ahola-Olli, Ari V.

AU - Barnes, Catriona L.K.

AU - Bertram, Lars

AU - Bis, Joshua C.

AU - Burdick, Katherine E.

AU - Christoforou, Andrea

AU - Derosse, Pamela

AU - Djurovic, Srdjan

AU - Espeseth, Thomas

AU - Giakoumaki, Stella

AU - Giddaluru, Sudheer

AU - Gustavson, Daniel E.

AU - Hayward, Caroline

AU - Hofer, Edith

AU - Ikram, M. Kamran

AU - Karlsson, Robert

AU - Knowles, Emma

AU - Lahti, Jari

AU - Leber, Markus

AU - Li, Shuo

AU - Mather, Karen A.

AU - Melle, Ingrid

AU - Morris, Derek

AU - Oldmeadow, Christopher

AU - Palviainen, Teemu

AU - Payton, Antony

AU - Pazoki, Raha

AU - Petrovic, Katja

AU - Reynolds, Chandra A.

AU - Sargurupremraj, Muralidharan

AU - Scholz, Markus

AU - Smith, Jennifer A.

AU - Smith, Albert V.

AU - Terzikhan, Natalie

AU - Thalamuthu, Anbupalam

AU - Trompet, Stella

AU - Van Der Lee, Sven J.

AU - Ware, Erin B.

AU - Windham, B. Gwen

AU - Wright, Margaret J.

AU - Yang, Jingyun

AU - Yu, Jin

AU - Ames, David

AU - Amin, Najaf

AU - Amouyel, Philippe

AU - Andreassen, Ole A.

AU - Armstrong, Nicola J.

AU - Assareh, Amelia A.

AU - Attia, John R.

AU - Attix, Deborah

AU - Avramopoulos, Dimitrios

AU - Bennett, David A.

AU - Böhmer, Anne C.

AU - Boyle, Patricia A.

AU - Brodaty, Henry

AU - Campbell, Harry

AU - Cannon, Tyrone D.

AU - Cirulli, Elizabeth T.

AU - Congdon, Eliza

AU - Conley, Emily Drabant

AU - Corley, Janie

AU - Cox, Simon R.

AU - Dale, Anders M.

AU - Dehghan, Abbas

AU - Dick, Danielle

AU - Dickinson, Dwight

AU - Eriksson, Johan G.

AU - Evangelou, Evangelos

AU - Faul, Jessica D.

AU - Ford, Ian

AU - Freimer, Nelson A.

AU - Gao, He

AU - Giegling, Ina

AU - Gillespie, Nathan A.

AU - Gordon, Scott D.

AU - Gottesman, Rebecca F.

AU - Griswold, Michael E.

AU - Gudnason, Vilmundur

AU - Harris, Tamara B.

AU - Hartmann, Annette M.

AU - Hatzimanolis, Alex

AU - Heiss, Gerardo

AU - Holliday, Elizabeth G.

AU - Joshi, Peter K.

AU - Kähönen, Mika

AU - Kardia, Sharon L.R.

AU - Karlsson, Ida

AU - Kleineidam, Luca

AU - Knopman, David S.

AU - Kochan, Nicole A.

AU - Konte, Bettina

AU - Kwok, John B.

AU - Le Hellard, Stephanie

AU - Lee, Teresa

AU - Lehtimäki, Terho

AU - Li, Shu Chen

AU - Liu, Tian

AU - Koini, Marisa

AU - London, Edythe

AU - Longstreth, Will T.

AU - Lopez, Oscar L.

AU - Loukola, Anu

AU - Luck, Tobias

AU - Lundervold, Astri J.

AU - Lundquist, Anders

AU - Lyytikäinen, Leo Pekka

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Murray, Alison D.

AU - Need, Anna C.

AU - Noordam, Raymond

AU - Nyberg, Lars

AU - Ollier, William

AU - Papenberg, Goran

AU - Pattie, Alison

AU - Polasek, Ozren

AU - Poldrack, Russell A.

AU - Psaty, Bruce M.

AU - Reppermund, Simone

AU - Riedel-Heller, Steffi G.

AU - Rose, Richard J.

AU - Rotter, Jerome I.

AU - Roussos, Panos

AU - Rovio, Suvi P.

AU - Saba, Yasaman

AU - Sabb, Fred W.

AU - Sachdev, Perminder S.

AU - Satizabal, Claudia L.

AU - Schmid, Matthias

AU - Scott, Rodney J.

AU - Scult, Matthew A.

AU - Simino, Jeannette

AU - Slagboom, P. Eline

AU - Smyrnis, Nikolaos

AU - Soumaré, Aïcha

AU - Stefanis, Nikos C.

AU - Stott, David J.

AU - Straub, Richard E.

AU - Sundet, Kjetil

AU - Taylor, Adele M.

AU - Taylor, Kent D.

AU - Tzoulaki, Ioanna

AU - Tzourio, Christophe

AU - Uitterlinden, André

AU - Vitart, Veronique

AU - Voineskos, Aristotle N.

AU - Kaprio, Jaakko

AU - Wagner, Michael

AU - Wagner, Holger

AU - Weinhold, Leonie

AU - Wen, K. Hoyan

AU - Widen, Elisabeth

AU - Yang, Qiong

AU - Zhao, Wei

AU - Adams, Hieab H.H.

AU - Arking, Dan E.

AU - Bilder, Robert M.

AU - Bitsios, Panos

AU - Boerwinkle, Eric

AU - Chiba-Falek, Ornit

AU - Corvin, Aiden

AU - De Jager, Philip L.

AU - Debette, Stéphanie

AU - Donohoe, Gary

AU - Elliott, Paul

AU - Fitzpatrick, Annette L.

AU - Gill, Michael

AU - Glahn, David C.

AU - Hägg, Sara

AU - Hansell, Narelle K.

AU - Hariri, Ahmad R.

AU - Ikram, M. Kamran

AU - Jukema, J. Wouter

AU - Vuoksimaa, Eero

AU - Keller, Matthew C.

AU - Kremen, William S.

AU - Launer, Lenore

AU - Lindenberger, Ulman

AU - Palotie, Aarno

AU - Pedersen, Nancy L.

AU - Pendleton, Neil

AU - Porteous, David J.

AU - Räikkönen, Katri

AU - Raitakari, Olli T.

AU - Ramirez, Alfredo

AU - Reinvang, Ivar

AU - Rudan, Igor

AU - Rujescu, Dan

AU - Schmidt, Reinhold

AU - Schmidt, Helena

AU - Schofield, Peter W.

AU - Schofield, Peter R.

AU - Starr, John M.

AU - Steen, Vidar M.

AU - Trollor, Julian N.

AU - Turner, Steven T.

AU - Van Duijn, Cornelia M.

AU - Villringer, Arno

AU - Weinberger, Daniel R.

AU - Weir, David R.

AU - Wilson, James F.

AU - Malhotra, Anil

AU - McIntosh, Andrew M.

AU - Gale, Catharine R.

AU - Seshadri, Sudha

AU - Mosley, Thomas H.

AU - Bressler, Jan

AU - Lencz, Todd

AU - Deary, Ian J.

N1 - Funding Information: This research was conducted in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, funded by the Biotechnology and Biological Sciences Research Council and Medical Research Council (MR/K026992/1). This research was conducted using the UK Biobank Resource (Application Nos. 10279 and 4844). The Neurology Working Group within the Cohorts for Heart and Aging Research in Genomic Epidemiology is partly supported by grants from the National Institute on Aging (R01 AG033193, U01 AG049505 and U01 AG052409). Cohort-specific acknowledgements are in Supplementary Note 3. Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048027481&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-04362-x

DO - 10.1038/s41467-018-04362-x

M3 - Journal articles

C2 - 29844566

AN - SCOPUS:85048027481

SN - 1751-8628

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2098

ER -

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

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