Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

Proitsi, P.; Lupton, M. K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Mk, Lupton; Tsolaki, Magda; Daniilidou, Makrina; Williams, J.; Pritchard, Megan; Harold, D.; Kloszewska, Iwona; Sims, R.; Gerrish, A.; Soininen, Hilkka; Chapman, J.; Escott-Price,; Mecocci, Patrizia; Vellas, Bruno; Abraham, R.; Hollingworth, P.; Hamshere, M.; Williams, A.; Singh Pahwa, J.; Dowzell, K.; Jones, N.; Thomas, C.; Williams, K.; Stretton, A.; Morgan, A.; Proitsi, Petroula; Lovestone, Simon; Lupton, Michelle K.; Powell, John F.; Brayne, C.; Rubinsztein, D. C.; Gill, M.; Lawlor, B.; Lynch, A.; Morgan, K.; Brown, K.; Passmore, P.; Craig, D.; Mcguinness, B.; Johnston, J. A.; Todd, S.; Holmes, C.; Mann, D.; Smith, A. D.; Love, S.; Kehoe, P. G.; Hardy, J.; Guerreiro, R.; Singleton, A.; Mead, S.; Fox, N.; Rossor, M.; Collinge, J.; Maier, W.; Jessen, F.; Heun, R.; Schürmann, B.; Wiltfang, J.; Initiative, Alzheimer's Disease Neuroimaging; Ramirez, A.; Becker, T.; Herold, C.; Lacour, A.; Drichel, D.; Van Den Bussche, H.; Heuser, I.; Kornhuber, J.; Gerad1, Consortium; Dichgans, M.; Frölich, L.; Hampel, H.; Hüll, M.; Rujescu, D.; Goate, A.; Kauwe, J. S. K.; Cruchaga, C.; Nowotny, P.; Morris, J. C.; Mayo, K.; Williams, Julie; Livingston, G.; Bass, N. J.; Gurling, H.; Mcquillin, A.; Gwilliam, R.; Deloukas, P.; Nöthen, M. M.; Holmans, P.; O'donovan, M.; Others,; Owen, M. J.; Stewart, Robert; Sham, Pak; Lovestone, S.; Jf, Powell; Powell, J. F.

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Public Library of Science, PLoS Medicine, 9(11), p. e1001713, 2014

DOI: 10.1371/journal.pmed.1001713

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Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

Journal article published in 2015 by P. Proitsi, M. K. Lupton, Latha Velayudhan

, Stephen Newhouse, Isabella Fogh, Lupton Mk, Magda Tsolaki, Makrina Daniilidou, J. Williams, Megan Pritchard, D. Harold

, Iwona Kloszewska, R. Sims, A. Gerrish, Hilkka Soininen and other authors.

This paper is made freely available by the publisher.

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Abstract

Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p

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Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

Abstract