title: Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals
creator: Holzinger, Emily R.
creator: Verma, Shefali S.
creator: Moore, Carrie B.
creator: Hall, Molly
creator: De, Rishika
creator: Gilbert-Diamond, Diane
creator: Lanktree, Matthew B.
creator: Pankratz, Nathan
creator: Amuzu, Antoinette
creator: Burt, Amber
creator: Dale, Caroline
creator: Dudek, Scott
creator: Furlong, Clement E.
creator: Gaunt, Tom R.
creator: Kim, Daniel S.
creator: Riess, Helene
creator: Sivapalaratnam, Suthesh
creator: Tragante, Vinicius
creator: van Iperen, Erik P. A.
creator: Brautbar, Ariel
creator: Carrell, David S.
creator: Crosslin, David R.
creator: Jarvik, Gail P.
creator: Kuivaniemi, Helena
creator: Kullo, Iftikhar J.
creator: Larson, Eric B.
creator: Rasmussen-Torvik, Laura J.
creator: Tromp, Gerard
creator: Baumert, Jens
creator: Cruickshanks, Karen J.
creator: Farrall, Martin
creator: Hingorani, Aroon D.
creator: Hovingh, G. K.
creator: Kleber, Marcus E.
creator: Klein, Barbara E.
creator: Klein, Ronald
creator: Koenig, Wolfgang
creator: Lange, Leslie A.
creator: Mӓrz, Winfried
creator: North, Kari E.
creator: Onland-Moret, N. Charlotte
creator: Reiner, Alex P.
creator: Talmud, Philippa J.
creator: van der Schouw, Yvonne T.
creator: Wilson, James G.
creator: Kivimaki, Mika
creator: Kumari, Meena
creator: Moore, Jason H.
creator: Drenos, Fotios
creator: Asselbergs, Folkert W.
creator: Keating, Brendan J.
creator: Ritchie, Marylyn D.
subject: ddc-570
subject: 570 Life sciences
description: Background: 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.
publisher: BioMed Central
date: 2017
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/23283/1/13040_2017_Article_145.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-232839
identifier:   Holzinger, Emily R. ; Verma, Shefali S. ; Moore, Carrie B. ; Hall, Molly ; De, Rishika ; Gilbert-Diamond, Diane ; Lanktree, Matthew B. ; Pankratz, Nathan ; Amuzu, Antoinette ; Burt, Amber ; Dale, Caroline ; Dudek, Scott ; Furlong, Clement E. ; Gaunt, Tom R. ; Kim, Daniel S. ; Riess, Helene ; Sivapalaratnam, Suthesh ; Tragante, Vinicius ; van Iperen, Erik P. A. ; Brautbar, Ariel ; Carrell, David S. ; Crosslin, David R. ; Jarvik, Gail P. ; Kuivaniemi, Helena ; Kullo, Iftikhar J. ; Larson, Eric B. ; Rasmussen-Torvik, Laura J. ; Tromp, Gerard ; Baumert, Jens ; Cruickshanks, Karen J. ; Farrall, Martin ; Hingorani, Aroon D. ; Hovingh, G. K. ; Kleber, Marcus E. ; Klein, Barbara E. ; Klein, Ronald ; Koenig, Wolfgang ; Lange, Leslie A. ; Mӓrz, Winfried ; North, Kari E. ; Onland-Moret, N. Charlotte ; Reiner, Alex P. ; Talmud, Philippa J. ; van der Schouw, Yvonne T. ; Wilson, James G. ; Kivimaki, Mika ; Kumari, Meena ; Moore, Jason H. ; Drenos, Fotios ; Asselbergs, Folkert W. ; Keating, Brendan J. ; Ritchie, Marylyn D.  (2017) Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals.  BioData Mining, 10 (25).  pp. 1-20.  ISSN 1756-0381     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/23283/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng