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Surakka, I.* ; Isaacs, A.* ; Karssen, L.C.* ; Laurila, P.P.* ; Middelberg, R.P.* ; 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, A.* ; Soranzo, N.* ; Heath, A.C.* ; Papamarkou, T.* ; Prokopenko, I.* ; Tönjes, A.* ; Kronenberg, F.* ; Döring, A. ; Rivadeneira, F.* ; Montgomery, G.W.* ; Whitfield, JB.* ; Kähönen, M.* ; Lehtimäki, T.* ; Freimer, N.B.* ; Willemsen, G.* ; de Geus, E.J.* ; Palotie, A.* ; Sandhu, M.S.* ; Waterworth, D.M.* ; Metspalu, A.* ; Stumvoll, M.* ; Uitterlinden, A.G.* ; Jula, A.* ; Navis, G.* ; Wijmenga, C.* ; Wolffenbuttel, B.H.* ; 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.* ; Eriksson, J.G.* ; Salomaa, V.* ; Oostra, B.A.* ; Raitakari, O.T.* ; Wichmann, H.-E. ; Gieger, C. ; Jarvelin, M.R.* ; Martin, N.G.* ; Hofman, A.* ; McCarthy, M.I.* ; Peltonen, L.* ; van Duijn, C.M.* ; Aulchenko, Y.S.* ; Ripatti, S* ; ENGAGE Consortium (*)

A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

PLoS Genet. 7:e1002333 (2011)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Density-lipoprotein cholesterol; HDL chloesterol; Association; Gene; Smoking; Plasma; Triglyeride; Obesity; Lipids; Polymorphisms
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 7, Issue: 10, Pages: , Article Number: e1002333 Supplement: ,
Publisher Public Library of Science (PLoS)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Institute of Epidemiology II (EPI2)