Education, intelligence and Alzheimer's disease: evidence from a multivariable two-sample Mendelian randomization study.
Education, intelligence and Alzheimer's disease: evidence from a multivariable two-sample Mendelian randomization study.
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DOI：
10.1093/ije/dyz280
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发表时间：
2020-08-01
影响因子：
7.7
通讯作者：
Hemani G
中科院分区：
文献类型：
--
作者：
Anderson EL;Howe LD;Wade KH;Ben-Shlomo Y;Hill WD;Deary IJ;Sanderson EC;Zheng J;Korologou-Linden R;Stergiakouli E;Davey Smith G;Davies NM;Hemani G
研究教育程度和智力是否对阿尔茨海默病 (AD) 风险具有独立的因果影响。双样本单变量和多变量孟德尔随机化 (MR)，用于估计教育对智力的因果影响，反之亦然，以及教育和智力对 AD 风险的总体和独立因果影响。来自国际阿尔茨海默病基因组学项目 (IGAP) 联盟的 17 008 例 AD 病例和 37 154 例对照。受教育年限（SD = 3.6 年）和智力（SD = 智力测试中的 15 分）每增加标准差，AD 的优势比 (OR)。有强有力的证据表明智力和教育程度之间存在因果、双向关系，两个方向的影响程度相似[教育智力的 OR = 0.51 SD 单位，95% 置信区间 (CI)：0.49，0.54；智力教育的 OR = 0.57 SD 单位，95% CI：0.48，0.66]。在单变量 MR 分析中，教育程度和智力对 AD 风险的总体影响相似；随着受教育年限和智力每增加一个 SD，AD 的几率平均分别降低 37%（95% CI：23-49%）和 35%（95% CI：25-43%）。多变量 MR 分析几乎没有证据表明，一旦考虑到智力，教育程度会影响 AD 风险（OR = 1.15，95% CI：0.68–1.93），但智力对 AD 风险的影响与教育程度无关，与单变量分析中观察到的程度相似（OR = 0.69，95% CI：0.44–0.88）。有强有力的证据表明智力在降低 AD 风险方面具有独立的因果作用。教育程度对 AD 风险的因果影响可能是通过智力来调节的。
To examine whether educational attainment and intelligence have causal effects on risk of Alzheimer’s disease (AD), independently of each other. Two-sample univariable and multivariable Mendelian randomization (MR) to estimate the causal effects of education on intelligence and vice versa, and the total and independent causal effects of both education and intelligence on AD risk. 17 008 AD cases and 37 154 controls from the International Genomics of Alzheimer’s Project (IGAP) consortium. Odds ratio (OR) of AD per standardized deviation increase in years of schooling (SD = 3.6 years) and intelligence (SD = 15 points on intelligence test). There was strong evidence of a causal, bidirectional relationship between intelligence and educational attainment, with the magnitude of effect being similar in both directions [OR for intelligence on education = 0.51 SD units, 95% confidence interval (CI): 0.49, 0.54; OR for education on intelligence = 0.57 SD units, 95% CI: 0.48, 0.66]. Similar overall effects were observed for both educational attainment and intelligence on AD risk in the univariable MR analysis; with each SD increase in years of schooling and intelligence, odds of AD were, on average, 37% (95% CI: 23–49%) and 35% (95% CI: 25–43%) lower, respectively. There was little evidence from the multivariable MR analysis that educational attainment affected AD risk once intelligence was taken into account (OR = 1.15, 95% CI: 0.68–1.93), but intelligence affected AD risk independently of educational attainment to a similar magnitude observed in the univariate analysis (OR = 0.69, 95% CI: 0.44–0.88). There is robust evidence for an independent, causal effect of intelligence in lowering AD risk. The causal effect of educational attainment on AD risk is likely to be mediated by intelligence.
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影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.
影响因子：
64.8
作者：
Okbay A;Beauchamp JP;Fontana MA;Lee JJ;Pers TH;Rietveld CA;Turley P;Chen GB;Emilsson V;Meddens SF;Oskarsson S;Pickrell JK;Thom K;Timshel P;de Vlaming R;Abdellaoui A;Ahluwalia TS;Bacelis J;Baumbach C;Bjornsdottir G;Brandsma JH;Pina Concas M;Derringer J;Furlotte NA;Galesloot TE;Girotto G;Gupta R;Hall LM;Harris SE;Hofer E;Horikoshi M;Huffman JE;Kaasik K;Kalafati IP;Karlsson R;Kong A;Lahti J;van der Lee SJ;deLeeuw C;Lind PA;Lindgren KO;Liu T;Mangino M;Marten J;Mihailov E;Miller MB;van der Most PJ;Oldmeadow C;Payton A;Pervjakova N;Peyrot WJ;Qian Y;Raitakari O;Rueedi R;Salvi E;Schmidt B;Schraut KE;Shi J;Smith AV;Poot RA;St Pourcain B;Teumer A;Thorleifsson G;Verweij N;Vuckovic D;Wellmann J;Westra HJ;Yang J;Zhao W;Zhu Z;Alizadeh BZ;Amin N;Bakshi A;Baumeister SE;Biino G;Bønnelykke K;Boyle PA;Campbell H;Cappuccio FP;Davies G;De Neve JE;Deloukas P;Demuth I;Ding J;Eibich P;Eisele L;Eklund N;Evans DM;Faul JD;Feitosa MF;Forstner AJ;Gandin I;Gunnarsson B;Halldórsson BV;Harris TB;Heath AC;Hocking LJ;Holliday EG;Homuth G;Horan MA;Hottenga JJ;de Jager PL;Joshi PK;Jugessur A;Kaakinen MA;Kähönen M;Kanoni S;Keltigangas-Järvinen L;Kiemeney LA;Kolcic I;Koskinen S;Kraja AT;Kroh M;Kutalik Z;Latvala A;Launer LJ;Lebreton MP;Levinson DF;Lichtenstein P;Lichtner P;Liewald DC;LifeLines Cohort Study;Loukola A;Madden PA;Mägi R;Mäki-Opas T;Marioni RE;Marques-Vidal P;Meddens GA;McMahon G;Meisinger C;Meitinger T;Milaneschi Y;Milani L;Montgomery GW;Myhre R;Nelson CP;Nyholt DR;Ollier WE;Palotie A;Paternoster L;Pedersen NL;Petrovic KE;Porteous DJ;Räikkönen K;Ring SM;Robino A;Rostapshova O;Rudan I;Rustichini A;Salomaa V;Sanders AR;Sarin AP;Schmidt H;Scott RJ;Smith BH;Smith JA;Staessen JA;Steinhagen-Thiessen E;Strauch K;Terracciano A;Tobin MD;Ulivi S;Vaccargiu S;Quaye L;van Rooij FJ;Venturini C;Vinkhuyzen AA;Völker U;Völzke H;Vonk JM;Vozzi D;Waage J;Ware EB;Willemsen G;Attia JR;Bennett DA;Berger K;Bertram L;Bisgaard H;Boomsma DI;Borecki IB;Bültmann U;Chabris CF;Cucca F;Cusi D;Deary IJ;Dedoussis GV;van Duijn CM;Eriksson JG;Franke B;Franke L;Gasparini P;Gejman PV;Gieger C;Grabe HJ;Gratten J;Groenen PJ;Gudnason V;van der Harst P;Hayward C;Hinds DA;Hoffmann W;Hyppönen E;Iacono WG;Jacobsson B;Järvelin MR;Jöckel KH;Kaprio J;Kardia SL;Lehtimäki T;Lehrer SF;Magnusson PK;Martin NG;McGue M;Metspalu A;Pendleton N;Penninx BW;Perola M;Pirastu N;Pirastu M;Polasek O;Posthuma D;Power C;Province MA;Samani NJ;Schlessinger D;Schmidt R;Sørensen TI;Spector TD;Stefansson K;Thorsteinsdottir U;Thurik AR;Timpson NJ;Tiemeier H;Tung JY;Uitterlinden AG;Vitart V;Vollenweider P;Weir DR;Wilson JF;Wright AF;Conley DC;Krueger RF;Davey Smith G;Hofman A;Laibson DI;Medland SE;Meyer MN;Yang J;Johannesson M;Visscher PM;Esko T;Koellinger PD;Cesarini D;Benjamin DJ
通讯作者：
Benjamin DJ
影响因子：
7.7
作者：
Lawlor DA
通讯作者：
Lawlor DA
影响因子：
3.5
作者：
Hemani G;Bowden J;Davey Smith G
通讯作者：
Davey Smith G