A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

I. Surakka, A. Isaacs, L.C. Karssen, P.P.P. Laurila, R.P.S. Middelberg, E. Tikkanen, J.S. Ried, C. Lamina, M. Mangino, W. Igl, J.J. Hottenga, V. Lagou, P. van der Harst, I. Mateo Leach, T. Esko, Z. Kutalik, N.W. Wainwright, M.V. Struchalin, A.P. Sarin, A.J. KangasJ.S. Viikari, M. Perola, T. Rantanen, A.K. Petersen, P. Soininen, Å. Johansson, N. Soranzo, A.C. Heath, T. Papamarkou, I. Prokopenko, A. Tönjes, F. Kronenberg, A. Döring, F. Rivadeneira, GW Montgomery, J.B. Whitfield, M. Kähönen, T. Lehtimäki, N.B. Freimer, G. Willemsen, E.J.C. de Geus, A. Palotie, M.S. Sandhu, D. Waterworth, A. Metspalu, M. Stumvoll, A.G. Uitterlinden, G. Navis, C. Wijmenga, B.H.R. Wolffenbuttel, M.R. Taskinen, M. Ala-Korpela, J. Kaprio, K.O. Kyvik, D.I. Boomsma, N.L. Pedersen, U. Gyllensten, J.F. Wilson, I. Rudan, H. Campbell, P.P. Pramstaller, T.D. Spector, J.C.M. Witteman, J.G. Eriksson, V. Salomaa, B.A. Oostra, O.T. Raitakari, H.E. Wichmann, C. Gieger, M.J. Järvelin, N.G. Martin, A. Hofman, M.I. McCarthy, L. Peltonen, C.M. van Duijn, Y.S. Aulchenko, S. Ripatti

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Abstract

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ~25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10
Original languageEnglish
Article numbere1002333
JournalPLoS Genetics
Volume7
Issue number10
DOIs
Publication statusPublished - 2011

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