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Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides

Nature Genetics volume 40, pages 149–151 (2008)Cite this article

Abstract

We tested over 267,000 SNPs in 1,005 Northern Europeans and 248,000 in 1,006 Indian Asians for association with triglycerides and HDL cholesterol, with replication in 10,536 subjects. We found association of a nonsynonymous SNP (rs3812316, G771C, Gln241His) in MLXIPL with plasma triglyceride levels (combined P = 1.4 × 10−10). MLXIPL coordinates transcriptional regulation of enzymes that channel glycolytic end-products into lipogenesis and energy storage, making MLXIPL a plausible 'thrifty gene'.

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Figure 1: Genomic context of the MLXIPL region on chromosome 7q11.23.

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Acknowledgements

At Ealing Hospital and Imperial College we thank J. Wrigley, S. Trainor and the team of research nurses for their excellent subject characterization and for sample handling, and D. Kalaitzopoulos, X. Li and P. Thomason for assistance with data analysis. At Pfizer we thank L.S. Wood, M.E. Lira and A.R. Mank-Seymour for their help, and D.S. Lee for strategic input. At Instituto Nacional de Ciencias Médicas y Nutrición, we thank O. Leyva, U. Alvirde, M.A. Melgarejo, L.E. Guillén, C. Moreno, C. Gonzalez, M.L. Velasco-Pérez and A. Velásquez for help with data collection, blood analysis and sample shipment. At Perlegen Sciences we thank L. Stuve, the laboratory group, R. Stokowski, the samples group, J. Sheehan, the data quality group, D. Ballinger, and the analysis and data pipeline group for excellent technical and infrastructural support and E. Beilharz for manuscript preparation. J.S.K., J.C.C., P.E. and J.S. were supported by the British Heart Foundation Grant SP/04/002.

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Author notes

  1. Gregory R Warnes & Patrice M Milos

    Present address: Current address: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York 14642, USA (G.R.W.); Helicos BioSciences, Cambridge, Massachusetts 02139, USA (P.M.M.).,

  2. Jaspal S Kooner and John C Chambers: These authors contributed equally to this work.

Authors and Affiliations

  1. National Heart and Lung Institute, Imperial College London, UK

    Jaspal S Kooner & James Scott

  2. Department of Epidemiology and Public Health, Imperial College London, UK

    John C Chambers & Paul Elliott

  3. Instituto Nacional de Ciencias Médicas y Nutrición, Vasco de Quiroga 15, México City, 14000, México

    Carlos A Aguilar-Salinas & Francisco J Gómez Pérez

  4. Perlegen Sciences, Inc., 2021 Stierlin Court, Mountain View, 94043, California, USA

    David A Hinds, Kelly A Frazer & David R Cox

  5. Pfizer Global Research and Development, Groton, 06340, Connecticut, USA

    Craig L Hyde, Gregory R Warnes, Patrice M Milos & John F Thompson

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Contributions

J.S.K., J.C.C., C.A.A.-S. and F.J.G.P. supervised patient recruitment and phenotyping. K.A.F. and J.F.T. supervised the experiments and, with J.S.K., J.S., D.R.C. and P.M.M., designed the study. D.A.H., C.L.H., G.R.W. and D.R.C. performed data analysis. J.S.K., J.C.C., P.E., P.M.M., J.S., K.A.F., D.A.H., D.R.C. and J.F.T. wrote the manuscript.

Corresponding author

Correspondence to Jaspal S Kooner.

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Competing interests

D.C.C. and D.A.H. are employees of Perlegen Sciences, Inc., J.F.T. and C.L.H. of Pfizer Inc., and P.M.M. of Helicos BioSciences.

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Supplementary Methods, Supplementary Figure 1 and Supplementary Tables 1–5 (PDF 597 kb)

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Kooner, J., Chambers, J., Aguilar-Salinas, C. et al. Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides. Nat Genet 40, 149–151 (2008). https://doi.org/10.1038/ng.2007.61

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