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. 2018 Sep 17;12(Suppl 9):35.
doi: 10.1186/s12919-018-0114-0. eCollection 2018.

Data for GAW20: genome-wide DNA sequence variation and epigenome-wide DNA methylation before and after fenofibrate treatment in a family study of metabolic phenotypes

Stella Aslibekyan  1 , Laura Almasy  2 , Michael A Province  3 , Devin M Absher  4 , Donna K Arnett  5
Affiliations

Data for GAW20: genome-wide DNA sequence variation and epigenome-wide DNA methylation before and after fenofibrate treatment in a family study of metabolic phenotypes

Stella Aslibekyan et al. BMC Proc. .

Abstract

GAW20 provided participants with an opportunity to comprehensively examine genetic and epigenetic variation among related individuals in the context of drug treatment response. GAW20 used data from 188 families (N = 1105) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (clinicaltrials.gov identifier NCT00083369), which included CD4+ T-cell DNA methylation at 463,995 cytosine-phosphate-guanine (CpG) sites measured before and after a 3-week treatment with fenofibrate, single-nucleotide variation at 906,600 loci, metabolic syndrome components ascertained before and after the drug intervention, and relevant covariates. All GOLDN participants were of European descent, with an average age of 48 years. In addition, approximately half were women and approximately 40% met the diagnostic criteria for metabolic syndrome. Unique advantages of the GAW20data set included longitudinal (3 weeks apart) measurements of DNA methylation, the opportunity to explore the contributions of both genotype and DNA methylation to the interindividual variability in drug treatment response, and the familial relationships between study participants. The principal disadvantage of GAW20/GOLDN data was the spurious correlation between batch effects and fenofibrate effects on methylation, which arose because the pre- and posttreatment methylation data were generated and normalized separately, and any attempts to remove time-dependent technical artifacts would also remove biologically meaningful changes brought on by fenofibrate. Despite this limitation, the GAW20 data set offered informative, multilayered omics data collected in a large population-based study of common disease traits, which resulted in creative approaches to integration and analysis of inherited human variation.

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Conflict of interest statement

Written informed consent was obtained from each GOLDN participant. The Institutional Review Board at each participating institution (University of Minnesota, University of Utah, and Tufts University/New England Medical Center) approved the study protocol.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Sequence and timing of interventions and clinic visits for the GOLDN study (not to scale). NMR, nuclear magnetic resonance; PPL, postprandial lipemia
See this image and copyright information in PMC

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