DOI: 10.1101/19004937Aug 17, 2019Paper

A gene-diet interaction-based score predicts response to dietary fat in the Women's Health Initiative

MedRxiv : the Preprint Server for Health Sciences
K. WestermanJose M. Ordovas


While diet response prediction for cardiometabolic risk factors (CRFs) has been demonstrated using single SNPs and main-effect genetic risk scores, little investigation has gone into the development of genome-wide diet response scores. We sought to leverage the multi-study setup of the Women's Health Initiative cohort to generate and test genetic scores for the response of six CRFs (body mass index, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and fasting glucose) to dietary fat. A genome-wide interaction study was undertaken for each CRF in women (n ~ 10000) not participating in the Dietary Modification (DM) trial, which focused on the reduction of dietary fat. Genetic scores based on these analyses were developed using a pruning-and-thresholding approach and tested for the prediction of one-year CRF changes as well as long-term chronic disease development in DM trial participants (n ~ 5000). One of these genetic scores, for LDL-cholesterol (LDL-C), predicted changes in the associated CRF. This 1760-variant score explained 3.4% of the variance in one-year LDL-C changes in the intervention arm, but was unassociated with changes in the control arm. In contrast, a main-effect genetic risk score for LD...Continue Reading

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