eprintid: 23283
rev_number: 11
eprint_status: archive
userid: 1589
dir: disk0/00/02/32/83
datestamp: 2017-08-03 09:20:36
lastmod: 2024-03-13 08:11:20
status_changed: 2017-08-03 09:20:36
type: article
metadata_visibility: show
creators_name: Holzinger, Emily R.
creators_name: Verma, Shefali S.
creators_name: Moore, Carrie B.
creators_name: Hall, Molly
creators_name: De, Rishika
creators_name: Gilbert-Diamond, Diane
creators_name: Lanktree, Matthew B.
creators_name: Pankratz, Nathan
creators_name: Amuzu, Antoinette
creators_name: Burt, Amber
creators_name: Dale, Caroline
creators_name: Dudek, Scott
creators_name: Furlong, Clement E.
creators_name: Gaunt, Tom R.
creators_name: Kim, Daniel S.
creators_name: Riess, Helene
creators_name: Sivapalaratnam, Suthesh
creators_name: Tragante, Vinicius
creators_name: van Iperen, Erik P. A.
creators_name: Brautbar, Ariel
creators_name: Carrell, David S.
creators_name: Crosslin, David R.
creators_name: Jarvik, Gail P.
creators_name: Kuivaniemi, Helena
creators_name: Kullo, Iftikhar J.
creators_name: Larson, Eric B.
creators_name: Rasmussen-Torvik, Laura J.
creators_name: Tromp, Gerard
creators_name: Baumert, Jens
creators_name: Cruickshanks, Karen J.
creators_name: Farrall, Martin
creators_name: Hingorani, Aroon D.
creators_name: Hovingh, G. K.
creators_name: Kleber, Marcus E.
creators_name: Klein, Barbara E.
creators_name: Klein, Ronald
creators_name: Koenig, Wolfgang
creators_name: Lange, Leslie A.
creators_name: Mӓrz, Winfried
creators_name: North, Kari E.
creators_name: Onland-Moret, N. Charlotte
creators_name: Reiner, Alex P.
creators_name: Talmud, Philippa J.
creators_name: van der Schouw, Yvonne T.
creators_name: Wilson, James G.
creators_name: Kivimaki, Mika
creators_name: Kumari, Meena
creators_name: Moore, Jason H.
creators_name: Drenos, Fotios
creators_name: Asselbergs, Folkert W.
creators_name: Keating, Brendan J.
creators_name: Ritchie, Marylyn D.
title: Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals
subjects: ddc-570
divisions: i-62600
abstract: 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.
date: 2017
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1655666533
own_urn: urn:nbn:de:bsz:16-heidok-232839
language: eng
bibsort: HOLZINGEREDISCOVERYA2017
full_text_status: public
publication: BioData Mining
volume: 10
number: 25
place_of_pub: London
pagerange: 1-20
issn: 1756-0381
citation:   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     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/23283/1/13040_2017_Article_145.pdf