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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The Genetic Analysis Workshop is funded by NIH R01 GM031575 (MacCluer & Almasy). The GOLDN study is funded by NIH R01 HL091357 (Arnett), NIH R01 HL104135 (Arnett), and NIH K01 HL136700 (Aslibekyan). Publication charges are paid by NIH R01 GM031575.
GOLDN data are publicly available in dbGaP at study accession number phs000741.v2.p1. Further information is available upon request. The data that support the findings of this study are available from the Genetic Analysis Workshop (GAW), but restrictions apply to the availability of these data, which were used under license for the current study. Qualified researchers may request these data directly from GAW.
Aslibekyan, Stella; Almasy, Laura; Province, Michael A.; Absher, Devin M.; and Arnett, Donna K., "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" (2018). Epidemiology and Environmental Health Faculty Publications. 40.