Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).
Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).
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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）。
DOI：
10.1038/mp.2014.188
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发表时间：
2015-02
影响因子：
11
通讯作者：
Deary, I. J.
中科院分区：
文献类型：
--
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.
一般认知功能在从青春期到老年的整个人类生命过程中基本上是可遗传的。我们调查了中年和老年人中这一重要的健康和幸福相关性状变异的遗传贡献。我们对31个队列（N= 53949）的全基因组关联研究进行了荟萃分析，其中参与者进行了多种多样的认知测试。一般认知功能表型进行了测试，并通过主成分分析在每个队列中创建。我们报道了在6q16.1、14 q12和19q13.32三个基因组区域中的13个全基因组显著的单核苷酸多态性（SNP）关联（最佳SNP和最接近的基因分别为：rs 10457441，P=3.93 × 10−9，MIR 2113; rs 17522122，P=2.55 × 10−8，AKAP 6; rs 10119，P=5.67 × 10−9，APOE/TOMM 40）。我们报告了一个与位于21号染色体上的HMGN 1基因（P=1 × 10−6）相关的基因。这些基因以前与神经精神表型相关。荟萃分析结果与多基因遗传模型一致。为了估计基于SNP的遗传力，将全基因组复杂性状分析程序应用于两个大型队列，社区研究中的动脉粥样硬化风险（N=6617）和健康与退休研究（N=5976）。所有基因分型的常见SNPs占表型变异的比例为29%（s.e.= 0.001）。5%）和28%（s.e.= 7%）。使用多基因预测分析，在苏格兰世代队列中预测了一般认知功能的~1.2%的方差（N=5487; P=1.5 × 10−17）。在假设驱动的测试中，一般认知功能与先前与阿尔茨海默病相关的四个基因之间存在显着关联：TOMM 40，APOE，ABCG 1和MEF 2C。
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 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). 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, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 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.
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APOE 位点遗传变异的功能分析表明区域增强子参与 TOMM40 和 APOE 的调节。
影响因子：
3.5
作者：
通讯作者：
--
影响因子：
4.1
作者：
Deary IJ;Gow AJ;Taylor MD;Corley J;Brett C;Wilson V;Campbell H;Whalley LJ;Visscher PM;Porteous DJ;Starr JM
通讯作者：
Starr JM
影响因子：
11
作者：
Davies G;Harris SE;Reynolds CA;Payton A;Knight HM;Liewald DC;Lopez LM;Luciano M;Gow AJ;Corley J;Henderson R;Murray C;Pattie A;Fox HC;Redmond P;Lutz MW;Chiba-Falek O;Linnertz C;Saith S;Haggarty P;McNeill G;Ke X;Ollier W;Horan M;Roses AD;Ponting CP;Porteous DJ;Tenesa A;Pickles A;Starr JM;Whalley LJ;Pedersen NL;Pendleton N;Visscher PM;Deary IJ
通讯作者：
Deary IJ
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
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