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

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Serval ID
serval:BIB_E9388E37E8FE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.
Journal
PLoS Genetics
Author(s)
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 J.B., 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., 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., Järvelin M.R., Martin N.G., Hofman A., McCarthy M.I., Peltonen L., van Duijn C.M., Aulchenko Y.S., Ripatti S.
Working group(s)
Taskinen M.R., ENGAGE Consortium
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
7
Number
10
Pages
e1002333
Language
english
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(-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.
Keywords
Adipose Tissue/metabolism, Body Fat Distribution, Cadherins/genetics, Cholesterol/blood, Cholesterol/genetics, Chromosome Mapping, Chromosomes, Human, Pair 4/genetics, European Continental Ancestry Group/genetics, Genome-Wide Association Study, Genotype, Humans, Lipids/blood, Lipids/genetics, Lipoproteins/blood, Lipoproteins/genetics, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics, Risk Factors, Triglycerides/blood, Triglycerides/genetics, Waist-Hip Ratio
Pubmed
Web of science
Open Access
Yes
Create date
12/03/2013 12:24
Last modification date
20/08/2019 16:11
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