Publication type
Journal Article
Authors
- Emily R. Holzinger
- Shefali S. Verma
- Carrie B. Moore
- Molly Hall
- Rishika De
- Diane Gilbert-Diamond
- Matthew B. Lanktree
- Nathan Pankratz
- Antoinette Amuzu
- Amber Burt
- Caroline Dale
- Scott Dudek
- Clement E. Furlong
- Tom R. Gaunt
- Daniel Seung Kim
- Helene Riess
- Suthesh Sivapalaratnam
- Vinicius Tragante
- Erik P.A. van Iperen
- Ariel Brautbar
- David S. Carrell
- David R. Crosslin
- Gail P. Jarvik
- Helena Kuivaniemi
- Iftikhar J. Kullo
- Eric B. Larson
- Laura J. Rasmussen-Torvik
- Gerard Tromp
- Jens Baumert
- Karen J. Cruickshanks
- Martin Farrall
- Aroon D. Hingorani
- G. K. Hovingh
- Marcus E. Kleber
- Barbara E. Klein
- Ronald Klein
- Wolfgang Koenig
- Leslie A. Lange
- Winfried MÓ“rz
- Kari E. North
- N. Charlotte Onland-Moret
- Alex P. Reiner
- Philippa J. Talmud
- Yvonne T. van der Schouw
- James G. Wilson
- Mika Kivimaki
- Meena Kumari
- Jason H. Moore
- Fotios Drenos
- Folkert W. Asselbergs
- Brendan J. Keating
- Marylyn D. Ritchie
Publication date
July 15, 2017
Summary:
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.
Published in
BioData Mining
Volume
Volume: 10:25
DOI
http://dx.doi.org/10.1186/s13040-017-0145-5
ISSN
17560381
Subject
Notes
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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