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

被引：453

作者：

Davies, Gail ^{[1
]}

Lam, Max ^{[2
]}

Harris, Sarah E. ^{[1
,13
]}

Trampush, Joey W. ^{[4
,5
]}

Luciano, Michelle ^{[1
]}

Hill, W. David ^{[1
]}

Hagenaars, Saskia P. ^{[1
,6
]}

Ritchie, Stuart J. ^{[1
]}

Marioni, Riccardo E. ^{[1
,3
]}

Fawns-Ritchie, Chloe ^{[1
]}

Liewald, David C. M. ^{[1
]}

Okely, Judith A. ^{[1
]}

Ahola-Olli, Ari V. ^{[7
,8
]}

Barnes, Catriona L. K. ^{[9
]}

Bertram, Lars ^{[10
]}

Bis, Joshua C. ^{[11
]}

Burdick, Katherine E. ^{[12
,13
,14
]}

Christoforou, Andrea ^{[15
,16
]}

DeRosse, Pamela ^{[2
,17
]}

Djurovic, Srdjan ^{[15
,18
]}

Espeseth, Thomas ^{[19
,20
]}

Giakoumaki, Stella ^{[21
]}

Giddaluru, Sudheer ^{[15
,16
]}

Gustavson, Daniel E. ^{[22
,23
]}

Hayward, Caroline ^{[24
,25
]}

Hofer, Edith ^{[26
,27
]}

Ikram, M. Arfan ^{[28
,29
,30
]}

Karlsson, Robert ^{[31
]}

Knowles, Emma ^{[32
]}

Lahti, Jari ^{[33
,34
]}

Leber, Markus ^{[35
]}

Li, Shuo ^{[36
]}

Mather, Karen A. ^{[37
]}

Melle, Ingrid ^{[15
,19
]}

Morris, Derek ^{[37
]}

Oldmeadow, Christopher ^{[39
,40
]}

Palviainen, Teemu ^{[41
]}

Payton, Antony ^{[42
]}

Pazoki, Raha ^{[43
]}

Petrovic, Katja ^{[26
]}

Reynolds, Chandra A. ^{[44
]}

Sargurupremraj, Muralidharan ^{[45
]}

Scholz, Markus ^{[46
,47
]}

Smith, Jennifer A. ^{[48
,49
]}

Smith, Albert V. ^{[50
,51
]}

Terzikhan, Natalie ^{[28
,52
]}

Thalamuthu, Anbupalam ^{[37
]}

Trompet, Stella ^{[53
]}

van der Lee, Sven J. ^{[28
]}

Ware, Erin B. ^{[49
]}

机构：

[1] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Dept Psychol, Sch Philosophy Psychol & Language Sci, Edinburgh EH8 9JZ, Midlothian, Scotland

[2] Inst Mental Hlth, Singapore 539747, Singapore

[3] Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Med Genet Sect,Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland

[4] BrainWorkup LLC, Los Angeles, CA 90033 USA

[5] Univ Southern Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA

[6] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, De Crespigny Pk,Denmark Hill, London SE5 8AF, England

[7] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland

[8] Satakunta Cent Hosp, Dept Internal Med, Pori 28100, Finland

[9] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland

[10] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[11] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA

[12] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[13] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 3, Bronx, NY 10468 USA

[14] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA

[15] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Psychosis Res, NORMENT, N-5021 Bergen, Norway

[16] Haukeland Hosp, Dr Einar Martens Res Grp Biol Psychiat, Ctr Med Genet & Mol Med, N-5020 Bergen, Norway

[17] Feinstein Inst Med Res, Ctr Psychiat Neurosc, Manhasset, NY 11030 USA

[18] Univ Bergen, Oslo Univ Hosp, Dept Med Genet, N-0424 Oslo, Norway

[19] Univ Oslo, Dept Psychol, N-0373 Oslo, Norway

[20] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0315 Oslo, Norway

[21] Univ Crete, Dept Psychol, GR-74100 Iraklion, Greece

[22] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA

[23] Univ Calif San Diego, Ctr Behav Genet Aging, San Diego, CA 92093 USA

[24] Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[25] Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh EH4 2XU, Midlothian, Scotland

[26] Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria

[27] Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria

[28] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3015 Rotterdam, Netherlands

[29] Erasmus Univ, Med Ctr, Dept Radiol & Nucl Med, NL-3015 Rotterdam, Netherlands

[30] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands

[31] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden

[32] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA

[33] Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki 00014, Finland

[34] Univ Helsinki, Helsinki Collegium Adv Studies, FIN-00014 Helsinki, Finland

[35] Univ Cologne, Dept Psychiat & Psychotherapy, D-50937 Cologne, Germany

[36] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[37] Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW 2031, Australia

[38] Natl Univ Ireland Galway, Sch Psychol & Discipline Biochem, Neuroimaging Cognit & Genom NICOG Ctr, Galway H91 TK33, Ireland

[39] Univ Newcastle, Med Res Inst, Callaghan, NSW 2308, Australia

[40] Univ Newcastle, Fac Hlth, Callaghan, NSW 2308, Australia

[41] Univ Helsinki, Inst Mol Med Finland FIMM, FL-00014 Helsinki, Finland

[42] Univ Manchester, Ctr Epidemiol, Hlth Serv Res & Primary Care, Div Populat Hlth, Manchester M13 9PL, Lancs, England

[43] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England

[44] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA

[45] Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, UMR 1219, F-33000 Bordeaux, France

[46] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany

[47] Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, D-04107 Leipzig, Germany

[48] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA

[49] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA

[50] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; REACTION-TIME; INTELLIGENCE DIFFERENCES; PROCESSING SPEED; COMMON VARIANTS; METAANALYSIS; SCHIZOPHRENIA; DISCOVERY; REVEALS; DCDC2;

D O I：

10.1038/s41467-018-04362-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 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.

引用

页数：16

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