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A gene-diet interaction-based score predicts response to dietary fat in the Women's Health Initiative.
Westerman, K, Liu, Q, Liu, S, Parnell, LD, Sebastiani, P, Jacques, P, DeMeo, DL, Ordovás, JM
The American journal of clinical nutrition. 2020;(4):893-902
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Abstract
BACKGROUND Although diet response prediction for cardiometabolic risk factors (CRFs) has been demonstrated using single genetic variants and main-effect genetic risk scores, little investigation has gone into the development of genome-wide diet response scores. OBJECTIVE We sought to leverage the multistudy setup of the Women's Health Initiative cohort to generate and test genetic scores for the response of 6 CRFs (BMI, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and fasting glucose) to dietary fat. METHODS A genome-wide interaction study was undertaken for each CRF in women (n ∼ 9000) 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 1-y CRF changes as well as long-term chronic disease development in DM trial participants (n ∼ 5000). RESULTS Only 1 of these genetic scores, for LDL cholesterol, predicted changes in the associated CRF. This 1760-variant score explained 3.7% (95% CI: 0.09, 11.9) of the variance in 1-y LDL cholesterol changes in the intervention arm but was unassociated with changes in the control arm. In contrast, a main-effect genetic risk score for LDL cholesterol was not useful for predicting dietary fat response. Further investigation of this score with respect to downstream disease outcomes revealed suggestive differential associations across DM trial arms, especially with respect to coronary heart disease and stroke subtypes. CONCLUSIONS These results lay the foundation for the combination of many genome-wide gene-diet interactions for diet response prediction while highlighting the need for further research and larger samples in order to achieve robust biomarkers for use in personalized nutrition.
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Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women.
Liu, Q, Lichtenstein, AH, Matthan, NR, Howe, CJ, Allison, MA, Howard, BV, Martin, LW, Valdiviezo, C, Manson, JE, Liu, S, et al
Lipids. 2017;(8):687-702
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Abstract
Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index [LI, defined as the sum of the products between FA levels and melting points (°C), divided by the total amount of FA: [Formula: see text]] is thought to reflect membrane and lipoprotein fluidity and may be associated with the risk of coronary heart disease (CHD). Therefore, we examined the associations of dietary and plasma phospholipid (PL) LI with CHD risk among postmenopausal women. We determined dietary LI for the cohort with completed baseline food frequency questionnaires and free of prevalent cardiovascular diseases in the Women's Health Initiative (WHI) observational study (N = 85,563). We additionally determined plasma PL LI in a matched case-control study (N = 2428) nested within the WHI observational cohort study. Cox proportional hazard regression and multivariable conditional logistic regression were used to calculate HRs/ORs for CHD risk between quartiles of LI after adjusting for potential sources of confounding and selection bias. Higher dietary LI in the cohort study and plasma PL LI in the case-control study were significantly associated with increased risk of CHD: HR = 1.18 (95% CI 1.07-1.31, P for trend <0.01) and OR = 1.76 (95% CI 1.33-2.33, P for trend <0.01) comparing extreme quartiles and adjusting for potential confounders. These associations still persisted after adjusting for the polyunsaturated to saturated fat ratio. Our study indicated that higher LI based on either dietary or plasma measurements, representing higher FA lipophilicity, was associated with elevated risk of CHD among postmenopausal women.