Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects.
Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects.
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DOI：
10.1093/aje/kwu283
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发表时间：
2015-02-15
影响因子：
5
通讯作者：
Thompson SG
中科院分区：
文献类型：
--
作者：
Burgess S;Thompson SG
传统的孟德尔随机化分析通过使用仅与感兴趣的风险因素相关的遗传变异作为工具变量来评估风险因素对结果的因果影响。然而，在某些情况下，例如甘油三酯水平是心血管疾病的风险因素，可能很难找到与相关风险因素不相关的相关基因变异，如其他脂质组分。这种变异被称为多效性。在本文中，我们提出了孟德尔随机化的一种扩展，它使用与几个测量的风险因素相关的多个遗传变量来同时估计每个风险因素对结果的因果影响。这种“多变量孟德尔随机化”方法类似于因子随机试验中对几种处理的同时评估。本文给出了估计因果效应的方法，并用实际数据和模拟数据进行了比较，并讨论了有效的多变量孟德尔随机化分析所必需的假设。根据这些假设，我们证明甘油三酯相关途径对冠心病风险有因果关系，而不受低密度脂蛋白胆固醇和高密度脂蛋白胆固醇的影响。
A conventional Mendelian randomization analysis assesses the causal effect of a risk factor on an outcome by using genetic variants that are solely associated with the risk factor of interest as instrumental variables. However, in some cases, such as the case of triglyceride level as a risk factor for cardiovascular disease, it may be difficult to find a relevant genetic variant that is not also associated with related risk factors, such as other lipid fractions. Such a variant is known as pleiotropic. In this paper, we propose an extension of Mendelian randomization that uses multiple genetic variants associated with several measured risk factors to simultaneously estimate the causal effect of each of the risk factors on the outcome. This “multivariable Mendelian randomization” approach is similar to the simultaneous assessment of several treatments in a factorial randomized trial. In this paper, methods for estimating the causal effects are presented and compared using real and simulated data, and the assumptions necessary for a valid multivariable Mendelian randomization analysis are discussed. Subject to these assumptions, we demonstrate that triglyceride-related pathways have a causal effect on the risk of coronary heart disease independent of the effects of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol.
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影响因子：
168.9
作者：
Sarwar, Nadeem;Sandhu, Manjinder S.;Ricketts, Sally L.;Butterworth, Adam S.;Di Angelantonio, Emanuele;Boelcholdt, S. Matthijs;Ouwehand, Willem;Watkins, Hugh;Samani, Nilesh J.;Saleheen, Danish;Lawlor, Debbie;Reilly, Muredach P.;Hingorani, Aroon D.;Talmud, Philippa J.;Danesh, John;Braund, P. S.;Hall, A. S.;Thompson, J.;Marz, W.;Sivapalaratnam, S.;Soranzo, N.;Trip, M.;Casas, J. P.;Ebrahim, S.;Arsenault, B. J.;Boekholdt, S. M.;Khaw, K. T.;Wareham, N. J.;Grallert, H.;Illig, T.;Humphries, S. E.;Rader, D. J.;He, J.;Clarke, R.;Hamsten, R.;Hopewell, J. C.;Frossard, P.;Deloukas, P.;Ye, S.;Simpson, J. A.;Onat, A.;Komurcu-Bayrak, E.;Martinelli, N.;Olivieri, O.;Girelli, D.;Kivimaki, M.;Kumari, M.;Aouizerat, B. E.;Baum, L.;Campos, H.;Chaaba, R.;Chen, B. S.;Cho, E. Y.;Evans, D.;Hill, J.;Hsu, L. A.;Hubacek, J. A.;Lai, C. Q.;Lee, J. H.;Klos, K.;Liu, H.;Masana, L.;Melegh, B.;Nabika, T.;Ribalta, J.;Ruiz-Narvaez, E.;Thomas, G. N.;Tomlinson, B.;Szalai, C.;Vaverkova, H.;Yamada, Y.;Yang, Y.;Tipping, R. W.;Ford, C. E.;Pressel, S. L.;Ballantyne, C.;Brautbar, A.;Knuiman, M.;Winchup, P. H.;Wannamethee, S. G.;Morris, R. W.;Kiechl, S.;Willeit, J.;Santer, P.;Mayr, A.;Wald, N.;Yarnell, J. W. G.;Gallacher, J.;Casiglia, E.;Tikhonoff, V.;Cushman, M.;Psaty, B. M.;Tracy, R. P.;Tybjaerg-Hansen, A.;Nordestgaard, B. G.;Benn, M.;Frikke-Schmidt, R.;Giampaoli, S.;Palmieri, L.;Panico, S.;Vanuzzo, D.;Pilotto, L.;Gomez de la Camara, A.;Gomez-Gerique, J. A.;Simons, L.;McCallum, J.;Friedlander, Y.;Fowkes, F. G. R.;Lee, A. J.;Taylor, J.;Guralnik, J. M.;Phillips, C. L.;Wallace, W. R.;Blazer, D. G.;Brenner, H.;Raum, E.;Mueller, H.;Rothenbacher, D.;Jansson, J. H.;Wennberg, P.;Nissinen, A.;Donfrancesco, C.;Salomaa, V.;Harald, K.;Pencina, M. J.;Vartiainen, E.;D'Agostino, R. B.;Vasan, R. S.;Bladbjerg, E. M.;Jorgensen, T.;Moller, L.;Jespersen, J.;Dankner, R.;Chetrit, A.;Lubin, F.;Bjoerkelund, C.;Lissner, L.;Bengtsson, C.;Cremer, P.;Nagel, D.;Rodriguez, B.;Dekker, J. M.;Nijpels, G.;Stehouwer, C. D. A.;Sato, S.;Iso, H.;Kitamura, A.;Noda, H.;Salonen, J. T.;Nyssoenen, K.;Tuimainen, T. -P.;Voutilainen, S.;Meade, T. W.;Cooper, J. A.;Kuller, L. H.;Grandits, G.;Gillum, R.;Mussolino, M.;Rimm, E.;Hankinson, S.;Manson, J. A. E.;Pai, J. K.;Bauer, K. A.;Naito, Y.;Amouyel, P.;Arveiler, D.;Evans, A.;Ferrieres, J.;Schulte, H.;Assmann, G.;Packard, C. J.;Sattar, N.;Westendorp, R. G.;Buckley, B. M.;Cantin, B.;Lamarche, B.;Despres, J. -P.;Dagenais, G. R.;Barrett-Connor, E.;Wingard, D. L.;Bettencourt, R.;Gudnason, V.;Aspelund, T.;Sigurdsson, G.;Thorsson, B.;Trevisan, M.;Tunstall-Pedoe, H.;Tavendale, R.;Lowe, G. D. O.;Woodward, M.;Howard, B. V.;Zhang, Y.;Best, L.;Umans, J.;Ben-Shlomo, Y.;Davey-Smith, G.;Njolstad, I.;Mathiesen, E. B.;Lochen, M. L.;Wilsgaard, T.;Ingelsson, E.;Lind, I.;Giedraitis, V.;Michaeelsson, K.;Brunner, E.;Shipley, M.;Ridker, P.;Buring, J.;Shepherd, J.;Cobbe, S. M.;Ford, I.;Robertson, M.;Marin Ibanez, A.;Feskens, E. J. M.;Kromhout, D.;Walker, M.;Watson, S.;Collins, R.;Kaptoge, S.;Perry, P. L.;Sarwar, N.;Thompson, A.;Thompson, S. G.;White, I. R.;Wood, A. M.
通讯作者：
Wood, A. M.
影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.
孟德尔随机分组：它如何 - 不能 - 螺旋 - 证实营养与癌症之间的因果关系。
DOI：
10.1158/1940-6207.capr-08-0070
发表时间：
2009-02
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Schatzkin A;Abnet CC;Cross AJ;Gunter M;Pfeiffer R;Gail M;Lim U;Davey-Smith G
通讯作者：
Davey-Smith G
影响因子：
7.7
作者：
Greenland, S
通讯作者：
Greenland, S
影响因子：
3.7
作者：
Burgess S;Freitag DF;Khan H;Gorman DN;Thompson SG
通讯作者：
Thompson SG