Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals

dc.contributor.authorHolzinger, Emily R.en_ZA
dc.contributor.authorVerma, Shefali S.en_ZA
dc.contributor.authorMoore, Carrie B.en_ZA
dc.contributor.authorHall, Mollyen_ZA
dc.contributor.authorDe, Rishikaen_ZA
dc.contributor.authorGilbert-Diamond, Dianeen_ZA
dc.contributor.authorLanktree, Matthew B.en_ZA
dc.contributor.authorPankratz, Nathanen_ZA
dc.contributor.authorAmuzu, Antoinetteen_ZA
dc.contributor.authorBurt, Amberen_ZA
dc.contributor.authorDale, Carolineen_ZA
dc.contributor.authorDudek, Scotten_ZA
dc.contributor.authorFurlong, Clement E.en_ZA
dc.contributor.authorGaunt, Tom R.en_ZA
dc.contributor.authorKim, Daniel Seungen_ZA
dc.contributor.authorRiess, Heleneen_ZA
dc.contributor.authorSivapalaratnam, Sutheshen_ZA
dc.contributor.authorTragante, Viniciusen_ZA
dc.contributor.authorVan Iperen, Erik P. A.en_ZA
dc.contributor.authorBrautba, Arielen_ZA
dc.contributor.authorCarrell, David S.en_ZA
dc.contributor.authorCrosslin, David R.en_ZA
dc.contributor.authorJarvik, Gail P.en_ZA
dc.contributor.authorKuivaniemi, Helenaen_ZA
dc.contributor.authorKullo, Iftikhar J.en_ZA
dc.contributor.authorLarson, Eric B.en_ZA
dc.contributor.authorRasmussen-Torvik, Laura J.en_ZA
dc.contributor.authorTromp, Gerarden_ZA
dc.contributor.authorBaumert, Jensen_ZA
dc.contributor.authorCruickshanks, Karen J.en_ZA
dc.contributor.authorFarrall, Martinen_ZA
dc.contributor.authorHingorani, Aroon D.en_ZA
dc.contributor.authorHovingh, G. K.en_ZA
dc.contributor.authorKleber, Marcus E.en_ZA
dc.contributor.authorKlein, Barbara E.en_ZA
dc.contributor.authorKlein, Ronalden_ZA
dc.contributor.authorKoenig, Wolfgangen_ZA
dc.contributor.authorLange, Leslie A.en_ZA
dc.contributor.authorMӓrz, Winfrieden_ZA
dc.contributor.authorNorth, Kari E.en_ZA
dc.contributor.authorOnland-Moret, N. Charlotteen_ZA
dc.contributor.authorReiner, Alex P.en_ZA
dc.contributor.authorTalmud, Philippa J.en_ZA
dc.contributor.authorVan Der Schouw, Yvonne T.en_ZA
dc.contributor.authorWilson, James G.en_ZA
dc.contributor.authorKivimaki, Mikaen_ZA
dc.contributor.authorKumari, Meenaen_ZA
dc.contributor.authorMoore, Jason H.en_ZA
dc.contributor.authorDrenos, Fotiosen_ZA
dc.contributor.authorAsselbergs, Folkert W.en_ZA
dc.contributor.authorKeating, Brendan J.en_ZA
dc.contributor.authorRitchie, Marylyn D.en_ZA
dc.identifier.citationHolzinger, E. R., et al. 2017. Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals. BioData Mining, 10:25, doi:10.1186/s13040-017-0145-5
dc.identifier.issn1756-0381 (online)
dc.descriptionCITATION: Holzinger, E. R., et al. 2017. Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals. BioData Mining, 10:25, doi:10.1186/s13040-017-0145-5.
dc.descriptionThe original publication is available at
dc.description.abstractBackground: The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). Results: Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing. Conclusions: These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication.en_ZA
dc.format.extent20 pages
dc.publisherBioMed Central
dc.subjectLipids in human nutritionen_ZA
dc.subjectGenetic epidemiologyen_ZA
dc.titleDiscovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individualsen_ZA
dc.description.versionPublisher's version
dc.rights.holderAuthors retain copyright

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