Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

被引：276

作者：

Davies, G. ^{[1
,2
]}

Armstrong, N. ^{[3
]}

Bis, J. C. ^{[4
]}

Bressler, J. ^{[5
]}

Chouraki, V. ^{[6
,7
]}

Giddaluru, S. ^{[8
,9
,10
]}

Hofer, E. ^{[11
,12
]}

Ibrahim-Verbaas, C. A. ^{[13
,14
]}

Kirin, M. ^{[15
]}

Lahti, J. ^{[16
,17
]}

van der Lee, S. J. ^{[14
]}

Le Hellard, S. ^{[8
,9
,10
]}

Liu, T. ^{[18
,19
]}

Marioni, R. E. ^{[1
,20
,21
]}

Oldmeadow, C. ^{[22
,23
]}

Postmus, I. ^{[24
,25
]}

Smith, A. V. ^{[26
,27
]}

Smith, J. A. ^{[28
]}

Thalamuthu, A. ^{[29
]}

Thomson, R. ^{[30
]}

Vitart, V. ^{[31
]}

Wang, J. ^{[32
,33
]}

Yu, L. ^{[34
]}

Zgaga, L. ^{[35
,36
]}

Zhao, W. ^{[28
]}

Boxall, R. ^{[20
]}

Harris, S. E. ^{[1
,20
]}

Hill, W. D. ^{[2
]}

Liewald, D. C. ^{[1
]}

Luciano, M. ^{[1
,2
]}

Adams, H. ^{[37
,38
]}

Ames, D. ^{[39
,40
]}

Amin, N. ^{[14
,38
]}

Amouyel, P. ^{[6
]}

Assareh, A. A. ^{[29
]}

Au, R. ^{[7
,32
]}

Becker, J. T. ^{[41
,42
,43
]}

Beiser, A. ^{[7
,32
]}

Berr, C. ^{[44
,45
]}

Bertram, L. ^{[19
,46
]}

Boerwinkle, E. ^{[5
,47
,48
]}

Buckley, B. M. ^{[49
]}

Campbell, H. ^{[15
]}

Corley, J. ^{[2
]}

De Jager, P. L. ^{[50
,51
,52
]}

Dufouil, C. ^{[53
,54
]}

Eriksson, J. G. ^{[17
,55
,56
,57
]}

Espeseth, T. ^{[58
,59
,60
]}

Faul, J. D. ^{[61
]}

Ford, I. ^{[62
]}

机构：

[1] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland

[2] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland

[3] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia

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

[5] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA

[6] Inst Pasteur, Inserm UMR744, Unite Epidemiol & Sante Publ, F-59019 Lille, France

[7] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[8] Univ Bergen, KG Jebsen Ctr Psychosis Res, Bergen, Norway

[9] Univ Bergen, Norwegian Ctr Mental Disorders Res NORMENT, Dept Clin Sci, Bergen, Norway

[10] Haukeland Hosp, Dr Einar Martens Res Grp Biol Psychiat, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

[11] Med Univ Graz, Dept Neurol, Graz, Austria

[12] Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria

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

[14] Erasmus Univ, Genet Epidemiol Unit, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands

[15] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9JZ, Midlothian, Scotland

[16] Univ Helsinki, Inst Behav Sci, Helsinki, Finland

[17] Folkhalsan Res Ctr, Helsinki, Finland

[18] Max Planck Inst Human Dev, Berlin, Germany

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

[20] Univ Edinburgh, Med Genet Sect, Ctr Genom & Expt Med, Inst Genet & Mol Med,Western Gen Hosp, Edinburgh EH8 9JZ, Midlothian, Scotland

[21] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[22] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia

[23] Univ Newcastle, Fac Hlth, Newcastle, NSW 2300, Australia

[24] Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands

[25] Netherlands Consortium Hlth Ageing, Leiden, Netherlands

[26] Iceland Heart Assoc, Kopavogur, Iceland

[27] Univ Iceland, Reykjavik, Iceland

[28] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA

[29] Univ New S Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia

[30] Menzies Res Inst, Hobart, Tas, Australia

[31] Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH8 9JZ, Midlothian, Scotland

[32] Framingham Heart Dis Epidemiol Study, Framingham, MA USA

[33] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[34] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

[35] Univ Dublin Trinity Coll, Dept Publ Hlth & Primary Care, Dublin 2, Ireland

[36] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia

[37] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[38] Netherlands Consortium Hlth Ageing, Leiden, Netherlands

[39] Royal Melbourne Hosp, Natl Ageing Res Inst, Melbourne, Vic, Australia

[40] Univ Melbourne, Acad Unit Psychiat Old Age, St Georges Hosp, Kew, Australia

[41] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA

[42] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA

[43] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA

[44] INSERM, U106, Montpellier, France

[45] Univ Montpellier I, Montpellier, France

[46] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, London, England

[47] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med Prevent Human Dis, Houston, TX 77030 USA

[48] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[49] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland

[50] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA

来源：

MOLECULAR PSYCHIATRY | 2015年 / 20卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; SUSCEPTIBILITY LOCI; IDENTIFIES VARIANTS; HUMAN INTELLIGENCE; TYPE-4; ALLELE; COMMON SNPS; AGE; MORTALITY; DECLINE;

D O I：

10.1038/mp.2014.188

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

引用

页码：183 / 192

页数：10

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