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

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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.

Author information

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.

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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