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. Kangas; J.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

doi:10.1371/journal.pgen.1002333

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

Biological Psychology

Research output: Contribution to Journal › Article › Academic › peer-review

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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 language	English
Article number	e1002333
Journal	PLoS Genetics
Volume	7
Issue number	10
DOIs	https://doi.org/10.1371/journal.pgen.1002333
Publication status	Published - 2011

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Surakka, I., Isaacs, A., Karssen, L. C., Laurila, P. P. P., Middelberg, R. P. S., Tikkanen, E., Ried, J. S., Lamina, C., Mangino, M., Igl, W., Hottenga, J. J., Lagou, V., van der Harst, P., Mateo Leach, I., Esko, T., Kutalik, Z., Wainwright, N. W., Struchalin, M. V., Sarin, A. P., ... Ripatti, S. (2011). A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol. PLoS Genetics, 7(10), [e1002333]. https://doi.org/10.1371/journal.pgen.1002333

Surakka, I. ; Isaacs, A. ; Karssen, L.C. ; Laurila, P.P.P. ; Middelberg, R.P.S. ; Tikkanen, E. ; Ried, J.S. ; Lamina, C. ; Mangino, M. ; Igl, W. ; Hottenga, J.J. ; Lagou, V. ; van der Harst, P. ; Mateo Leach, I. ; Esko, T. ; Kutalik, Z. ; Wainwright, N.W. ; Struchalin, M.V. ; Sarin, A.P. ; Kangas, A.J. ; Viikari, J.S. ; Perola, M. ; Rantanen, T. ; Petersen, A.K. ; Soininen, P. ; Johansson, Å. ; Soranzo, N. ; Heath, A.C. ; Papamarkou, T. ; Prokopenko, I. ; Tönjes, A. ; Kronenberg, F. ; Döring, A. ; Rivadeneira, F. ; Montgomery, GW ; Whitfield, J.B. ; Kähönen, M. ; Lehtimäki, T. ; Freimer, N.B. ; Willemsen, G. ; de Geus, E.J.C. ; Palotie, A. ; Sandhu, M.S. ; Waterworth, D. ; Metspalu, A. ; Stumvoll, M. ; Uitterlinden, A.G. ; Navis, G. ; Wijmenga, C. ; Wolffenbuttel, B.H.R. ; Taskinen, M.R. ; Ala-Korpela, M. ; Kaprio, J. ; Kyvik, K.O. ; Boomsma, D.I. ; Pedersen, N.L. ; Gyllensten, U. ; Wilson, J.F. ; Rudan, I. ; Campbell, H. ; Pramstaller, P.P. ; Spector, T.D. ; Witteman, J.C.M. ; Eriksson, J.G. ; Salomaa, V. ; Oostra, B.A. ; Raitakari, O.T. ; Wichmann, H.E. ; Gieger, C. ; Järvelin, M.J. ; Martin, N.G. ; Hofman, A. ; McCarthy, M.I. ; Peltonen, L. ; van Duijn, C.M. ; Aulchenko, Y.S. ; Ripatti, S. / A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol. In: PLoS Genetics. 2011 ; Vol. 7, No. 10.

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

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",

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

year = "2011",

doi = "10.1371/journal.pgen.1002333",

language = "English",

volume = "7",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "10",

}

Surakka, I, Isaacs, A, Karssen, LC, Laurila, PPP, Middelberg, RPS, Tikkanen, E, Ried, JS, Lamina, C, Mangino, M, Igl, W, Hottenga, JJ, Lagou, V, van der Harst, P, Mateo Leach, I, Esko, T, Kutalik, Z, Wainwright, NW, Struchalin, MV, Sarin, AP, Kangas, AJ, Viikari, JS, Perola, M, Rantanen, T, Petersen, AK, Soininen, P, Johansson, Å, Soranzo, N, Heath, AC, Papamarkou, T, Prokopenko, I, Tönjes, A, Kronenberg, F, Döring, A, Rivadeneira, F, Montgomery, GW, Whitfield, JB, Kähönen, M, Lehtimäki, T, Freimer, NB, Willemsen, G , de Geus, EJC, Palotie, A, Sandhu, MS, Waterworth, D, Metspalu, A, Stumvoll, M, Uitterlinden, AG, Navis, G, Wijmenga, C, Wolffenbuttel, BHR, Taskinen, MR, Ala-Korpela, M, Kaprio, J, Kyvik, KO, Boomsma, DI, Pedersen, NL, Gyllensten, U, Wilson, JF, Rudan, I, Campbell, H, Pramstaller, PP, Spector, TD, Witteman, JCM, Eriksson, JG, Salomaa, V, Oostra, BA, Raitakari, OT, Wichmann, HE, Gieger, C, Järvelin, MJ, Martin, NG, Hofman, A, McCarthy, MI, Peltonen, L, van Duijn, CM, Aulchenko, YS & Ripatti, S 2011, 'A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol', PLoS Genetics, vol. 7, no. 10, e1002333. https://doi.org/10.1371/journal.pgen.1002333

A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol. / Surakka, I.; Isaacs, A.; Karssen, L.C.; Laurila, P.P.P.; Middelberg, R.P.S.; Tikkanen, E.; Ried, J.S.; Lamina, C.; Mangino, M.; Igl, W.; Hottenga, J.J.; Lagou, V.; van der Harst, P.; Mateo Leach, I.; Esko, T.; Kutalik, Z.; Wainwright, N.W.; Struchalin, M.V.; Sarin, A.P.; Kangas, A.J.; Viikari, J.S.; Perola, M.; Rantanen, T.; Petersen, A.K.; Soininen, P.; Johansson, Å.; Soranzo, N.; Heath, A.C.; Papamarkou, T.; Prokopenko, I.; Tönjes, A.; Kronenberg, F.; Döring, A.; Rivadeneira, F.; Montgomery, GW; Whitfield, J.B.; Kähönen, M.; Lehtimäki, T.; Freimer, N.B.; Willemsen, G.; de Geus, E.J.C.; Palotie, A.; Sandhu, M.S.; Waterworth, D.; Metspalu, A.; Stumvoll, M.; Uitterlinden, A.G.; Navis, G.; Wijmenga, C.; Wolffenbuttel, B.H.R.; Taskinen, M.R.; Ala-Korpela, M.; Kaprio, J.; Kyvik, K.O.; Boomsma, D.I.; Pedersen, N.L.; Gyllensten, U.; Wilson, J.F.; Rudan, I.; Campbell, H.; Pramstaller, P.P.; Spector, T.D.; Witteman, J.C.M.; Eriksson, J.G.; Salomaa, V.; Oostra, B.A.; Raitakari, O.T.; Wichmann, H.E.; Gieger, C.; Järvelin, M.J.; Martin, N.G.; Hofman, A.; McCarthy, M.I.; Peltonen, L.; van Duijn, C.M.; Aulchenko, Y.S.; Ripatti, S.

In: PLoS Genetics, Vol. 7, No. 10, e1002333, 2011.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

AU - Surakka, I.

AU - Isaacs, A.

AU - Karssen, L.C.

AU - Laurila, P.P.P.

AU - Middelberg, R.P.S.

AU - Tikkanen, E.

AU - Ried, J.S.

AU - Lamina, C.

AU - Mangino, M.

AU - Igl, W.

AU - Hottenga, J.J.

AU - Lagou, V.

AU - van der Harst, P.

AU - Mateo Leach, I.

AU - Esko, T.

AU - Kutalik, Z.

AU - Wainwright, N.W.

AU - Struchalin, M.V.

AU - Sarin, A.P.

AU - Kangas, A.J.

AU - Viikari, J.S.

AU - Perola, M.

AU - Rantanen, T.

AU - Petersen, A.K.

AU - Soininen, P.

AU - Johansson, Å.

AU - Soranzo, N.

AU - Heath, A.C.

AU - Papamarkou, T.

AU - Prokopenko, I.

AU - Tönjes, A.

AU - Kronenberg, F.

AU - Döring, A.

AU - Rivadeneira, F.

AU - Montgomery, GW

AU - Whitfield, J.B.

AU - Kähönen, M.

AU - Lehtimäki, T.

AU - Freimer, N.B.

AU - Willemsen, G.

AU - de Geus, E.J.C.

AU - Palotie, A.

AU - Sandhu, M.S.

AU - Waterworth, D.

AU - Metspalu, A.

AU - Stumvoll, M.

AU - Uitterlinden, A.G.

AU - Navis, G.

AU - Wijmenga, C.

AU - Wolffenbuttel, B.H.R.

AU - Taskinen, M.R.

AU - Ala-Korpela, M.

AU - Kaprio, J.

AU - Kyvik, K.O.

AU - Boomsma, D.I.

AU - Pedersen, N.L.

AU - Gyllensten, U.

AU - Wilson, J.F.

AU - Rudan, I.

AU - Campbell, H.

AU - Pramstaller, P.P.

AU - Spector, T.D.

AU - Witteman, J.C.M.

AU - Eriksson, J.G.

AU - Salomaa, V.

AU - Oostra, B.A.

AU - Raitakari, O.T.

AU - Wichmann, H.E.

AU - Gieger, C.

AU - Järvelin, M.J.

AU - Martin, N.G.

AU - Hofman, A.

AU - McCarthy, M.I.

AU - Peltonen, L.

AU - van Duijn, C.M.

AU - Aulchenko, Y.S.

AU - Ripatti, S.

PY - 2011

Y1 - 2011

N2 - 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

AB - 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

U2 - 10.1371/journal.pgen.1002333

DO - 10.1371/journal.pgen.1002333

M3 - Article

VL - 7

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 10

M1 - e1002333

ER -