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Nat Commun. 2018 May 29;9(1):2098. doi: 10.1038/s41467-018-04362-x.

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

Davies G1, Lam M2, Harris SE1,3, Trampush JW4,5, Luciano M1, Hill WD1, Hagenaars SP1,6, Ritchie SJ1, Marioni RE1,3, Fawns-Ritchie C1, Liewald DCM1, Okely JA1, Ahola-Olli AV7,8, Barnes CLK9, Bertram L10, Bis JC11, Burdick KE12,13,14, Christoforou A15,16, DeRosse P2,17, Djurovic S15,18, Espeseth T19,20, Giakoumaki S21, Giddaluru S15,16, Gustavson DE22,23, Hayward C24,25, Hofer E26,27, Ikram MA28,29,30, Karlsson R31, Knowles E32, Lahti J33,34, Leber M35, Li S36, Mather KA37, Melle I15,19, Morris D38, Oldmeadow C39, Palviainen T40, Payton A41, Pazoki R42, Petrovic K26, Reynolds CA43, Sargurupremraj M44, Scholz M45,46, Smith JA47,48, Smith AV49,50, Terzikhan N28,51, Thalamuthu A37, Trompet S52, van der Lee SJ28, Ware EB48, Windham BG53, Wright MJ54,55, Yang J56,57, Yu J17, Ames D58,59, Amin N28, Amouyel P60, Andreassen OA19,61, Armstrong NJ62, Assareh AA37, Attia JR63, Attix D64,65, Avramopoulos D66,67, Bennett DA56,57, Böhmer AC68,69, Boyle PA56,70, Brodaty H37,71, Campbell H9, Cannon TD72, Cirulli ET73, Congdon E74, Conley ED75, Corley J1, Cox SR1, Dale AM22,76,77,78, Dehghan A42,79, Dick D80, Dickinson D81, Eriksson JG82,83,84,85, Evangelou E42,82, Faul JD48, Ford I86, Freimer NA74, Gao H42, Giegling I87, Gillespie NA88, Gordon SD89, Gottesman RF90,91, Griswold ME92, Gudnason V49,50, Harris TB93, Hartmann AM87, Hatzimanolis A94,95,96, Heiss G97, Holliday EG63, Joshi PK9, Kähönen M98,99,100, Kardia SLR47, Karlsson I31, Kleineidam L101,102,103,104, Knopman DS105, Kochan NA37,106, Konte B87, Kwok JB107,108, Le Hellard S15,16, Lee T37,106, Lehtimäki T109,110, Li SC111,112, Liu T10,111, Koini M26, London E74, Longstreth WT Jr113,114, Lopez OL115, Loukola A40, Luck T46,116, Lundervold AJ117,118, Lundquist A119,120, Lyytikäinen LP109,110, Martin NG89, Montgomery GW89,121, Murray AD25,122, Need AC123, Noordam R52, Nyberg L119,124,125, Ollier W126, Papenberg G111,127, Pattie A128, Polasek O129,130, Poldrack RA131, Psaty BM11,132,133, Reppermund S37,134, Riedel-Heller SG116, Rose RJ135, Rotter JI136,137, Roussos P12,138,139, Rovio SP7, Saba Y140, Sabb FW141, Sachdev PS37,106, Satizabal CL142,143, Schmid M144, Scott RJ63, Scult MA145, Simino J92, Slagboom PE146, Smyrnis N94,95, Soumaré A44, Stefanis NC94,95,96, Stott DJ147, Straub RE148, Sundet K19,20, Taylor AM128, Taylor KD136,137, Tzoulaki I42,79,149, Tzourio C44,150, Uitterlinden A28,151, Vitart V24, Voineskos AN152, Kaprio J40,82,153, Wagner M103,104, Wagner H102, Weinhold L144, Wen KH28, Widen E40, Yang Q36, Zhao W47, Adams HHH28,154, Arking DE67, Bilder RM74, Bitsios P155, Boerwinkle E156,157, Chiba-Falek O64, Corvin A158, De Jager PL159,160, Debette S44,161, Donohoe G38, Elliott P42,79, Fitzpatrick AL114,162, Gill M158, Glahn DC32, Hägg S31, Hansell NK54, Hariri AR145, Ikram MK28,30, Jukema JW163, Vuoksimaa E40,153, Keller MC164, Kremen WS22,23, Launer L93, Lindenberger U111, Palotie A40,165,166, Pedersen NL31, Pendleton N167, Porteous DJ1,3,25, Räikkönen K33, Raitakari OT7,168, Ramirez A35,68,102, Reinvang I20, Rudan I9, Dan Rujescu87, Schmidt R26, Schmidt H140, Schofield PW169, Schofield PR170,171, Starr JM1,172, Steen VM15,16, Trollor JN37,134, Turner ST173, Van Duijn CM28, Villringer A174,175, Weinberger DR148, Weir DR48, Wilson JF9,24, Malhotra A17,176,177, McIntosh AM1,178, Gale CR1,179, Seshadri S142,143,180, Mosley TH Jr53, Bressler J156, Lencz T17,178, Deary IJ181.

Author information

1
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.
2
Institute of Mental Health, Singapore, 539747, Singapore.
3
Medical Genetics Section, Centre for Genomic & Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
4
BrainWorkup, LLC, Los Angeles, 90033, CA, USA.
5
Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, 90033, CA, USA.
6
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
7
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
8
Department of Internal Medicine, Satakunta Central Hospital, Pori, 28100, Finland.
9
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
10
Max Planck Institute for Molecular Genetics, Berlin, 14195, Germany.
11
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, 98101, Washington, USA.
12
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
13
Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, 10468, NY, USA.
14
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, USA.
15
NORMENT, K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, 5021, Norway.
16
Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, 5020, Norway.
17
Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, 11030, NY, USA.
18
Department of Medical Genetics, Oslo University Hospital, University of Bergen, Oslo, 0424, Norway.
19
Department of Psychology, University of Oslo, Oslo, 0373, Norway.
20
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, 0315, Norway.
21
Department of Psychology, University of Crete, Crete, GR-74100, Greece.
22
Department of Psychiatry, University of California, San Diego, 92093, CA, USA.
23
Center for Behavior Genetics of Aging, University of California, San Diego, 92093, CA, USA.
24
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
25
Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
26
Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz, Graz, 8036, Austria.
27
Institute of Medical Informatics Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
28
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015, The Netherlands.
29
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, 3015, The Netherlands.
30
Department of Neurology, Erasmus University Medical Center, Rotterdam, xxxxxx, The Netherlands.
31
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SE-171 77, Sweden.
32
Department of Psychiatry, Yale University School of Medicine, New Haven, 06511, CT, USA.
33
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
34
Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00014, Finland.
35
Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, D-50937, Germany.
36
Department of Biostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.
37
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, 2031, Australia.
38
Neuroimaging, Cognition & Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, H91 TK33, Ireland.
39
Medical Research Institute and Faculty of Health, University of Newcastle, New South Wa0les, 2308, Australia.
40
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, FI-00014, Finland.
41
Centre for EpidemiologyDivision of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, M13 9PL, UK.
42
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, W2 1PG, UK.
43
Department of Psychology, University of California Riverside, Riverside, 92521, CA, USA.
44
University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219, F-33000, Bordeaux, France.
45
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, 04107, Germany.
46
LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04107, Germany.
47
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
48
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
49
Icelandic Heart Association, Kopavogur, IS-201, Iceland.
50
University of Iceland, Reykjavik, 101, Iceland.
51
Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
52
Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2333, The Netherlands.
53
Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
54
Queensland Brain Institute, University of Queensland, Brisbane, 4072, Australia.
55
Centre for Advanced Imaging, University of Queensland, Brisbane, 4072, Australia.
56
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, 60612, IL, USA.
57
Department of Neurological Sciences, Rush University Medical Center, Chicago, 60612, IL, USA.
58
National Ageing Research Institute, Royal Melbourne Hospital, Victoria, 3052, Australia.
59
Academic Unit for Psychiatry of Old Age, University of Melbourne, St George's Hospital, Kew, 3010, Australia.
60
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-LabEx DISTALZ, F-59000, Lille, France.
61
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, 0372, Norway.
62
Mathematics and Statistics, Murdoch University, Perth, 6150, Australia.
63
Hunter Medical Research Institute and Faculty of Health, University of Newcastle, New South Wales, 2305, Australia.
64
Department of NeurologyBryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center, Durham, 27708, NC, USA.
65
Psychiatry and Behavioral Sciences, Division of Medical Psychology, and Department of Neurology, Duke University Medical Center, Durham, 27708, NC, USA.
66
Department of Psychiatry, Johns Hopkins University School of Medicine, MD, Baltimore, 21287, USA.
67
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, 21287, USA.
68
Institute of Human Genetics, University of Bonn, Bonn, 53113, Germany.
69
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, 53113, Germany.
70
Departments of Behavioral Sciences, Rush University Medical Center, Chicago, 60612, IL, USA.
71
Dementia Centre for Research Collaboration, University of New South Wales, Sydney, 2031, NSW, Australia.
72
Department of Psychology, Yale University, New Haven, 06520, CT, USA.
73
Human Longevity Inc, Durham, 27709, NC, USA.
74
UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, 90024, CA, USA.
75
23andMe, Inc., Mountain View, 94041, CA, USA.
76
Department of Cognitive Science, University of California, San Diego, La Jolla, 92093, CA, USA.
77
Department of Neurosciences, University of California, San Diego, La Jolla, 92093, CA, USA.
78
Department of Radiology, University of California, San Diego, La Jolla, 92093, CA, USA.
79
MRC-PHE Centre for Environment, School of Public Health, Imperial College London, London, W2 1PG, UK.
80
Department of Psychology, Virginia Commonwealth University, Richmond, 23284, VA, USA.
81
Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, 20892, MD, USA.
82
National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
83
Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, 00290, Finland.
84
Helsinki University Central Hospital, Unit of General Practice, Helsinki, FI-00029, Finland.
85
Folkhälsan Research Centre, Helsinki, 2018, Finland.
86
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
87
Department of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, 06108, Germany.
88
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298, VA, USA.
89
QIMR Berghofer Medical Research Institute, Brisbane, 4029, Australia.
90
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
91
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, MD, USA.
92
Department of Data Science, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
93
Intramural Research Program National Institutes on Aging, National Institutes of Health, Bethesda, 20892, MD, USA.
94
Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, 11528, Greece.
95
University Mental Health Research Institute, Athens, GR-156 01, Greece.
96
Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, 11521, Greece.
97
Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27599, NC, USA.
98
Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center, Tampere, FI-33014, Finland.
99
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33521, Finland.
100
Department of Clinical Physiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
101
Department of Psychiatry Medical Faculty, University of Cologne, Cologne, 50923, Germany.
102
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, 53127, Germany.
103
German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Germany.
104
Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, 53127, Germany.
105
Department of Neurology, Mayo Clinic, Rochester, 55905, MN, USA.
106
Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, 2031, Australia.
107
Brain and Mind Centre-The University of Sydney, Camperdown, NSW, 2050, Australia.
108
School of Medical Sciences, University of New South Wales, Sydney, 2052, Australia.
109
Department of Clinical Chemistry, Fimlab Laboratories, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
110
Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
111
Max Planck Institute for Human Development, Berlin, 14195, Germany.
112
Technische Universität Dresden, Dresden, 01187, Germany.
113
Department of Neurology, School of Medicine, University of Washington, Seattle, 98195-6465, WA, USA.
114
Department of Epidemiology, University of Washington, Seattle, 98195, WA, USA.
115
Department of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
116
Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, 04103, Germany.
117
Department of Biological and Medical Psychology, University of Bergen, Bergen, 5009, Norway.
118
K. G. Jebsen Center for Neuropsychiatry, University of Bergen, Bergen, N-5009, Norway.
119
Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, SE-901 87, Sweden.
120
Department of Statistics, USBE Umeå University, S-907 97, Umeå, Sweden.
121
Institute for Molecular Bioscience, University of Queensland, Brisbane, 4072, Australia.
122
The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
123
Division of Brain Sciences, Department of Medicine, Imperial College, London, SW7 2AZ, UK.
124
Department of Radiation Sciences, Umeå University, Umeå, SE-901 87, Sweden.
125
Department of Integrative Medical Biology, Umeå University, Umeå, SE-901 87, Sweden.
126
Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, M13 9PT, UK.
127
Karolinska Institutet, Aging Research Center, Stockholm University, Stockholm, SE-113 30, Sweden.
128
Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
129
Gen-Info LLC, Zagreb, 10000, Croatia.
130
Faculty of Medicine, University of Split, Split, 21000, Croatia.
131
Department of Psychology, Stanford University, Palo Alto, 94305-2130, CA, USA.
132
Deparment of Health Services, University of Washington, Seattle, 98195-7660, WA, USA.
133
Kaiser Permanente Washington Health Research Institute, Seattle, 98101, WA, USA.
134
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, 2052, Australia.
135
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405-7007, USA.
136
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
137
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, 90509, CA, USA.
138
Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
139
Mental Illness Research, Education, and Clinical Center (VISN 2), James J. Peters VA Medical Center, Bronx, 10468, NY, USA.
140
Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8036, Austria.
141
Robert and Beverly Lewis Center for Neuroimaging, University of Oregon, Eugene, 97403, OR, USA.
142
Department of Neurology, Boston University School of Medicine, Boston, 02118, MA, USA.
143
The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, 01702-5827, MA, USA.
144
Department of Medical Biometry, Informatics and Epidemiology, University Hospital, Bonn, D-53012, Germany.
145
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, 27708-0086, NC, USA.
146
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
147
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
148
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, 21205, MD, USA.
149
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
150
Department of Public Health, University Hospital of Bordeaux, Bordeaux, 33076, France.
151
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
152
Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, M5T 1L8, Canada.
153
Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
154
Department of Radiology, Erasmus MC, Rotterdam, 3015, The Netherlands.
155
Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, GR-71003, Greece.
156
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
157
Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030-3411, TX, USA.
158
Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, DO2 AY89, Ireland.
159
Center for Translational and Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, 10032, NY, USA.
160
Program in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.
161
Department of Neurology, University Hospital of Bordeaux, Bordeaux, 33000, France.
162
Department of Global Health, University of Washington, Seattle, 98104, WA, USA.
163
Department of Cardiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
164
Institute for Behavioral Genetics, University of Colorado, Boulder, 80309, CO, USA.
165
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
166
Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, 00014, Finland.
167
Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Manchester Academic Health Science Centre, and Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester, Manchester, M13 9PL, UK.
168
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20520, Finland.
169
School of Medicine and Public Health, University of Newcastle, New South Wales, 2308, Australia.
170
Neuroscience Research Australia, Sydney, 2031, Australia.
171
Faculty of Medicine, University of New South Wales, Sydney, 2052, Australia.
172
Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
173
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
174
Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, 04103, Germany.
175
Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, 04103, Germany.
176
Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, 11004, NY, USA.
177
Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, 11549, NY, USA.
178
Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK.
179
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK.
180
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, 78229, TX, USA.
181
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. i.deary@ed.ac.uk.

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.

PMID:
29844566
PMCID:
PMC5974083
DOI:
10.1038/s41467-018-04362-x
[Indexed for MEDLINE]
Free PMC Article

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