Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

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dc.contributor"European Union (EU)" and "Horizon 2020"
dc.contributor.authorShungin, Dmitry
dc.contributor.authorDeng, Wei Q.
dc.contributor.authorVarga, Tibor V.
dc.contributor.authorLuan, Jian'an
dc.contributor.authorMihailov, Evelin
dc.contributor.authorMetspalu, Andres
dc.contributor.authorGIANT Consortium
dc.contributor.authorMorris, Andrew P.
dc.contributor.authorForouhi, Nita G.
dc.contributor.authorLindgren, Cecilia
dc.contributor.authorMagnusson, Patrik K. E.
dc.contributor.authorPedersen, Nancy L.
dc.contributor.authorHallmans, Göran
dc.contributor.authorChu, Audrey Y.
dc.contributor.authorJustice, Anne E.
dc.contributor.authorGraff, Mariaelisa
dc.contributor.authorWinkler, Thomas W.
dc.contributor.authorRose, Lynda M.
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorCupples, L. Adrienne
dc.contributor.authorKilpeläinen, Tuomas O.
dc.contributor.authorScott, Robert A.
dc.contributor.authorMägi, Reedik
dc.contributor.authorParé, Guillaume
dc.contributor.authorFranks, Paul W.
dc.contributor.authorRidker, Paul M.
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorOng, Ken K.
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorIngelsson, Erik
dc.date.accessioned2019-02-27T10:27:43Z
dc.date.available2019-02-27T10:27:43Z
dc.date.issued2017
dc.description.abstractPhenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman’s ρ = 0.401 for triglycerides, and ρ = 0.236 for BMI) compared to all SNPs. When Pv and Pm were compared for all pruned SNPs, only BMI was statistically significant (Spearman’s ρ = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the Pv distribution (Pbinomial <0.05). SNPs from the top 1% of the Pm distribution for BMI had more significant Pv values (PMann–Whitney = 1.46×10−5), and the odds ratio of SNPs with nominally significant (<0.05) Pm and Pv was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant G×E interaction P-values (Pint<0.05) were enriched with nominally significant Pv values (Pbinomial = 8.63×10−9 and 8.52×10−7 for SNP × smoking and SNP × physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for G×E, and variance-based prioritization can be used to identify them.et
dc.identifier.urihttps://doi.org/10.1371/journal.pgen.1006812
dc.identifier.urihttp://hdl.handle.net/10062/63439
dc.language.isoenget
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/692065///WIDENLIFEet
dc.relation.ispartofseriesPLoS Genet. 2017 Jun;13(6)
dc.rightsinfo:eu-repo/semantics/openAccesset
dc.subjectMolecular geneticset
dc.subjectPhysical activityet
dc.subjectCholesterolet
dc.subjectQuantitative trait lociet
dc.subjectMeta-analysiset
dc.subjectConsortiaet
dc.subjectLipoproteinset
dc.titleRanking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactionset
dc.typeinfo:eu-repo/semantics/articleet

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