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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dc.contributor.author Surakka, Ida -
dc.contributor.author Isaacs, Aaron -
dc.contributor.author Karssen, Lennart C -
dc.contributor.author Kähönen, Mika (Tay) -
dc.contributor.author Lehtimäki, Terho (Tay) -
dc.date.accessioned 2012-06-17T20:14:38Z
dc.date.available 2012-06-16 16:16:17 -
dc.date.available 2012-06-17T20:14:38Z
dc.date.issued 2011 -
dc.identifier.issn 1553-7404 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/65962
dc.description Public Library of Science -
dc.description.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. -
dc.language.iso en -
dc.title A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-717 -
dc.identifier.doi 10.1371/journal.pgen.1002333 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Biolääketieteet | en=Biomedicine| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title PLoS Genetics -
dc.journal.volume 7 -
dc.journal.number 10 -
dc.journal.volumepagerange 1-8 -
dc.oldstats 43 -

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