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dc.contributor.authorSurakka I
dc.contributor.authorIsaacs A
dc.contributor.authorKarssen LC
dc.contributor.authorLaurila PP
dc.contributor.authorMiddelberg RP
dc.contributor.authorTikkanen E
dc.contributor.authorRied JS
dc.contributor.authorLamina C
dc.contributor.authorMangino M
dc.contributor.authorIgl W
dc.contributor.authorHottenga JJ
dc.contributor.authorLagou V
dc.contributor.authorvan der Harst P
dc.contributor.authorMateo Leach I
dc.contributor.authorEsko T
dc.contributor.authorKutalik Z
dc.contributor.authorWainwright NW
dc.contributor.authorStruchalin MV
dc.contributor.authorSarin AP
dc.contributor.authorKangas AJ
dc.contributor.authorViikari JS
dc.contributor.authorPerola M
dc.contributor.authorRantanen T
dc.contributor.authorPetersen AK
dc.contributor.authorSoininen P
dc.contributor.authorJohansson A
dc.contributor.authorSoranzo N
dc.contributor.authorHeath AC
dc.contributor.authorPapamarkou T
dc.contributor.authorProkopenko I
dc.contributor.authorTönjes A
dc.contributor.authorKronenberg F
dc.contributor.authorDöring A
dc.contributor.authorRivadeneira F
dc.contributor.authorMontgomery GW
dc.contributor.authorWhitfield JB
dc.contributor.authorKähönen M
dc.contributor.authorLehtimäki T
dc.contributor.authorFreimer NB
dc.contributor.authorWillemsen G
dc.contributor.authorde Geus EJ
dc.contributor.authorPalotie A
dc.contributor.authorSandhu MS
dc.contributor.authorWaterworth DM
dc.contributor.authorMetspalu A
dc.contributor.authorStumvoll M
dc.contributor.authorUitterlinden AG
dc.contributor.authorJula A
dc.contributor.authorNavis G
dc.contributor.authorWijmenga C
dc.contributor.authorWolffenbuttel BH
dc.contributor.authorTaskinen MR
dc.contributor.authorAla-Korpela M
dc.contributor.authorKaprio J
dc.contributor.authorKyvik KO
dc.contributor.authorBoomsma DI
dc.contributor.authorPedersen NL
dc.contributor.authorGyllensten U
dc.contributor.authorWilson JF
dc.contributor.authorRudan I
dc.contributor.authorCampbell H
dc.contributor.authorPramstaller PP
dc.contributor.authorSpector TD
dc.contributor.authorWitteman JC
dc.contributor.authorEriksson JG
dc.contributor.authorSalomaa V
dc.contributor.authorOostra BA
dc.contributor.authorRaitakari OT
dc.contributor.authorWichmann HE
dc.contributor.authorGieger C
dc.contributor.authorJärvelin MR
dc.contributor.authorMartin NG
dc.contributor.authorHofman A
dc.contributor.authorMcCarthy MI
dc.contributor.authorPeltonen L
dc.contributor.authorvan Duijn CM
dc.contributor.authorAulchenko YS
dc.contributor.authorRipatti S
dc.contributor.authorENGAGE Consortium
dc.date.accessioned2018-10-30T10:56:28Z
dc.date.available2018-10-30T10:56:28Z
dc.date.issued2011
dc.identifier.issn1553-7390
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pgen.1002333
dc.identifier.urihttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002333
dc.identifier.urihttp://hdl.handle.net/10863/6754
dc.description.abstractRecent 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.en_US
dc.language.isoenen_US
dc.rights
dc.titleA genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterolen_US
dc.typeArticleen_US
dc.date.updated2018-10-30T10:29:31Z
dc.language.isiEN-GB
dc.journal.titlePLoS genetics
dc.description.fulltextopenen_US


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