Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Record number 455652
Title Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease
Author(s) Meurs, J.B.J. van; Pare, G.; Schwartz, S.M.; Hazra, A.; Tanaka, T.; Vermeulen, S.H.; Cotlarciuc, I.; Yuan, X.; Malarstig, A.; Bandinelli, S.; Bis, J.C.; Morn, H.; Brown, M.J.; Chen, C.; Chen, Y.D.; Clarke, R.J.; Dehghan, A.; Erdmann, J.; Ferrucci, L.; Hamsten, A.; Hofman, A.; Hunten, D.J.; Goel, A.; Johnson, A.D.; Kathiresan, S.; Kampman, E.; Kiel, D.P.; Kiemeney, L.A.; Chambers, J.C.; Kraft, P.; Lindemans, J.; McKnight, B.; Nelson, C.P.; O'Donnell, C.J.; Psaty, B.M.; Ridken, P.M.; Rivadeneira, F.; Rose, L.M.; Seedoif, U.; Siscovick, D.S.; Schunkert, H.; Selhub, J.; Ueland, P.M.; Vollenweiden, P.; Waeben, G.; Waterworth, D.M.; Watkins, H.; Witteman, J.C.M.; Heijen, M. den; Jacques, P.; Uitterlinden, A.G.; Koonet, J.S.; Rader, D.J.; Reilly, M.P.; Moose, V.; Chasman, D.I.; Samani, N.J.; Ahmadi, K.R.
Source American Journal of Clinical Nutrition 98 (2013)3. - ISSN 0002-9165 - p. 668 - 676.
Department(s) Visserij
Nutrition and Disease
Publication type Refereed Article in a scientific journal
Publication year 2013
Keyword(s) genome-wide association - cardiovascular-disease - mendelian randomization - heart-disease - expression - metaanalysis - mthfr - polymorphism - women - identification
Abstract Background: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteinelowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. Objective: We tested whether common genetic polymorphisms associated with variation in tlicy are also associated with CAD. Design: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymolphisms associated with tHcy (P <10(-8)) were tested for association with CAD in 31,400 cases and 92,927 controls. Results: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 X 10(-9)), SLC17A3 (1.0 x 10(-8)), GTPB10 (1.7 X 10(-8)), CUBN (7.5 X 10(-1)), HNFlA (1.2 x 10(-12)), and FUT2 (6.6 x 10(-9)), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-gmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 X 10(-36)). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). Conclusions: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHey concentrations and tHcy-related pathways for CAD.
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