Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
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DOI：
10.1038/s41467-018-04362-x
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发表时间：
2018-05-29
影响因子：
16.6
通讯作者：
Deary IJ
中科院分区：
文献类型：
--
作者：
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 MA;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;Lill CM;Liu T;Koini M;London E;Longstreth WT Jr;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;Dan Rujescu;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 Jr;Bressler J;Lencz T;Deary IJ
一般认知功能是一种突出且相对稳定的人类特征，与许多重要的生活结果相关。我们联合收割机来自CHARGE和COGENT联盟以及英国生物库（总N = 300，486;年龄16-102）的认知和遗传数据，发现了148个与一般认知功能相关的全基因组显著独立位点（P < 5 × 10−8）。在新的遗传基因座中，有与神经退行性和神经发育障碍、身体和精神疾病以及大脑结构相关的变异。基于基因的分析发现709个基因与一般认知功能相关。大脑皮层的表达水平与一般认知功能有关。使用多基因评分，在独立样本中预测一般认知功能的方差高达4.3%。我们检测到一般认知功能，反应时间和许多健康变量（包括视力，高血压和寿命）之间存在显着的遗传重叠。总之，我们确定了新的遗传位点和途径，有助于一般认知功能的遗传性。认知功能与健康和重要的生活结果有关。在这里，作者对300，486名个体的一般认知功能进行了全基因组关联研究，并确定了与该特征相关的神经和细胞发育途径的遗传位点。
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. Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.
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影响因子：
11
作者：
Davies G;Marioni RE;Liewald DC;Hill WD;Hagenaars SP;Harris SE;Ritchie SJ;Luciano M;Fawns-Ritchie C;Lyall D;Cullen B;Cox SR;Hayward C;Porteous DJ;Evans J;McIntosh AM;Gallacher J;Craddock N;Pell JP;Smith DJ;Gale CR;Deary IJ
通讯作者：
Deary IJ
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
64.8
作者：
Deary, Ian J.;Yang, Jian;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
对一般认知功能变异的遗传贡献：电荷联盟中全基因组关联研究的荟萃分析（n = 53949）。
影响因子：
11
作者：
Davies, G.;Armstrong, N.;Bis, J. C.;Bressler, J.;Chouraki, V.;Giddaluru, S.;Hofer, E.;Ibrahim-Verbaas, C. A.;Kirin, M.;Lahti, J.;van der Lee, S. J.;Le Hellard, S.;Liu, T.;Marioni, R. E.;Oldmeadow, C.;Postmus, I.;Smith, A. V.;Smith, J. A.;Thalamuthu, A.;Thomson, R.;Vitart, V.;Wang, J.;Yu, L.;Zgaga, L.;Zhao, W.;Boxall, R.;Harris, S. E.;Hill, W. D.;Liewald, D. C.;Luciano, M.;Adams, H.;Ames, D.;Amin, N.;Amouyel, P.;Assareh, A. A.;Au, R.;Becker, J. T.;Beiser, A.;Berr, C.;Bertram, L.;Boerwinkle, E.;Buckley, B. M.;Campbell, H.;Corley, J.;De Jager, P. L.;Dufouil, C.;Eriksson, J. G.;Espeseth, T.;Faul, J. D.;Ford, I.;Gottesman, R. F.;Griswold, M. E.;Gudnason, V.;Harris, T. B.;Heiss, G.;Hofman, A.;Holliday, E. G.;Huffman, J.;Kardia, S. L. R.;Kochan, N.;Knopman, D. S.;Kwok, J. B.;Lambert, J-C;Lee, T.;Li, G.;Li, S-C;Loitfelder, M.;Lopez, O. L.;Lundervold, A. J.;Lundqvist, A.;Mather, K. A.;Mirza, S. S.;Nyberg, L.;Oostra, B. A.;Palotie, A.;Papenberg, G.;Pattie, A.;Petrovic, K.;Polasek, O.;Psaty, B. M.;Redmond, P.;Reppermund, S.;Rotter, J. I.;Schmidt, H.;Schuur, M.;Schofield, P. W.;Scott, R. J.;Steen, V. M.;Stott, D. J.;Van Swieten, J. C.;Taylor, K. D.;Trollor, J.;Trompet, S.;Uitterlinden, A. G.;Weinstein, G.;Widen, E.;Windham, B. G.;Jukema, J. W.;Wright, A. F.;Wright, M. J.;Yang, Q.;Amieva, H.;Attia, J. R.;Bennett, D. A.;Brodaty, H.;de Craen, A. J. M.;Hayward, C.;Ikram, M. A.;Lindenberger, U.;Nilsson, L-G;Porteous, D. J.;Raikkonen, K.;Reinvang, I.;Rudan, I.;Sachdev, P. S.;Schmidt, R.;Schofield, P. R.;Srikanth, V.;Starr, J. M.;Turner, S. T.;Weir, D. R.;Wilson, J. F.;Van Duijn, C.;Launer, L.;Fitzpatrick, A. L.;Seshadri, S.;Mosley, T. H., Jr.;Deary, I. J.
通讯作者：
Deary, I. J.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium