scholarly journals Interactions Between Enhanced Polygenic Risk Scores and Lifestyle for Cardiovascular Disease, Diabetes, and Lipid Levels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yixuan Ye ◽  
Xi Chen ◽  
James Han ◽  
Wei Jiang ◽  
Pradeep Natarajan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Reduction ◽  
Genetic Risk ◽  
Absolute Risk ◽  
Absolute Risk Reduction ◽  
Risk Scores ◽  
Polygenic Risk ◽  
The Absolute ◽  
Additive Interactions

Background: Both lifestyle and genetic factors confer risk for cardiovascular diseases, type 2 diabetes, and dyslipidemia. However, the interactions between these 2 groups of risk factors were not comprehensively understood due to previous poor estimation of genetic risk. Here we set out to develop enhanced polygenic risk scores (PRS) and systematically investigate multiplicative and additive interactions between PRS and lifestyle for coronary artery disease, atrial fibrillation, type 2 diabetes, total cholesterol, triglyceride, and LDL-cholesterol. Methods: Our study included 276 096 unrelated White British participants from the UK Biobank. We investigated several PRS methods (P+T, LDpred, PRS continuous shrinkage, and AnnoPred) and showed that AnnoPred achieved consistently improved prediction accuracy for all 6 diseases/traits. With enhanced PRS and combined lifestyle status categorized by smoking, body mass index, physical activity, and diet, we investigated both multiplicative and additive interactions between PRS and lifestyle using regression models. Results: We observed that healthy lifestyle reduced disease incidence by similar multiplicative magnitude across different PRS groups. The absolute risk reduction from lifestyle adherence was, however, significantly greater in individuals with higher PRS. Specifically, for type 2 diabetes, the absolute risk reduction from lifestyle adherence was 12.4% (95% CI, 10.0%–14.9%) in the top 1% PRS versus 2.8% (95% CI, 2.3%–3.3%) in the bottom PRS decile, leading to a ratio of >4.4. We also observed a significant interaction effect between PRS and lifestyle on triglyceride level. Conclusions: By leveraging functional annotations, AnnoPred outperforms state-of-the-art methods on quantifying genetic risk through PRS. Our analyses based on enhanced PRS suggest that individuals with high genetic risk may derive similar relative but greater absolute benefit from lifestyle adherence.

scholarly journals Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population

Diabetologia ◽  
2010 ◽  
Vol 53 (10) ◽  
pp. 2155-2162 ◽  
Author(s):  
B. Fontaine-Bisson ◽  
◽  
F. Renström ◽  
O. Rolandsson ◽  
F. Payne ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Risk ◽  
Risk Scores ◽  
Discriminative Power ◽  
Swedish Population ◽  
Genetic Risk Scores

scholarly journals SNP-Based Genetic Risk Score Modeling Suggests No Increased Genetic Susceptibility of the Roma Population to Type 2 Diabetes Mellitus

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 942 ◽  
Author(s):  
Nardos Abebe Werissa ◽  
Peter Piko ◽  
Szilvia Fiatal ◽  
Zsigmond Kosa ◽  
Janos Sandor ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
General Population ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Unhealthy Lifestyle ◽  
Roma Population

Background: In a previous survey, an elevated fasting glucose level (FG) and/or known type 2 diabetes mellitus (T2DM) were significantly more frequent in the Roma population than in the Hungarian general population. We assessed whether the distribution of 16 single nucleotide polymorphisms (SNPs) with unequivocal effects on the development of T2DM contributes to this higher prevalence. Methods: Genetic risk scores, unweighted (GRS) and weighted (wGRS), were computed and compared between the study populations. Associations between GRSs and FG levels and T2DM status were investigated in separate and combined study populations. Results: The Hungarian general population carried a greater genetic risk for the development of T2DM (GRSGeneral = 15.38 ± 2.70 vs. GRSRoma = 14.80 ± 2.68, p < 0.001; wGRSGeneral = 1.41 ± 0.32 vs. wGRSRoma = 1.36 ± 0.31, p < 0.001). In the combined population models, GRSs and wGRSs showed significant associations with elevated FG (p < 0.001) and T2DM (p < 0.001) after adjusting for ethnicity, age, sex, body mass index (BMI), high-density Lipoprotein Cholesterol (HDL-C), and triglyceride (TG). In these models, the effect of ethnicity was relatively strong on both outcomes (FG levels: βethnicity = 0.918, p < 0.001; T2DM status: ORethnicity = 2.484, p < 0.001). Conclusions: The higher prevalence of elevated FG and/or T2DM among Roma does not seem to be directly linked to their increased genetic load but rather to their environmental/cultural attributes. Interventions targeting T2DM prevention among Roma should focus on harmful environmental exposures related to their unhealthy lifestyle.

scholarly journals Dietary and genetic risk scores and incidence of type 2 diabetes

2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Ulrika Ericson ◽  
George Hindy ◽  
Isabel Drake ◽  
Christina-Alexandra Schulz ◽  
Louise Brunkwall ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Risk ◽  
Risk Scores ◽  
Genetic Risk Scores

scholarly journals P.150 Use of Antibacterial Envelopes for Prevention of Infection in Neuromodulation

2021 ◽  
Vol 48 (s3) ◽  
pp. S63-S63
Author(s):  
A Persad ◽  
S Ahmed ◽  
R Mercure-Cyr ◽  
K Waterhouse ◽  
A Vitali
Keyword(s):  
Risk Reduction ◽  
Infection Rate ◽  
Pulse Generator ◽  
Absolute Risk ◽  
Absolute Risk Reduction ◽  
Historical Cohort ◽  
Cardiac Devices ◽  
Pump Placement ◽  
Substantial Risk ◽  
The Absolute

Background: Neuromodulation unit placement carries a historic infection rate as high as 12%. TYRX antibacterial envelopes (Medtronic Inc., Minneapolis, MN), which are absorbable mesh envelopes that elute minocycline and rifampin, have been used in implantable cardiac devices with substantial risk reduction for infection. Methods: We conducted a retrospective cohort study of consecutive implantable pulse generator (IPG) and intrathecal pump unit implantation with a TYRX antibacterial envelope©. This cohort was then compared to a historical cohort of consecutive patients undergoing IPG or pump placement or revision prior to the use of the envelopes. Results: In the pre-envelope cohort of 151 IPGs in 116 patients, the infection rate was 18/151 (11.9%). In the antibacterial envelope cohort of 233 IPGs in 185 patients, the infection rate was (2.1%). The absolute risk reduction was 4.6% (95% CI, 0.045-0.048), The pre-envelope cohort of 41 pumps in 39 patients, the infection rate was 6/41 (14.6%). In the antibacterial envelope cohort of 59 pumps in 54 patients, the infection rate was (1.7%). The absolute risk reduction was 12.9% (95% CI 1.6-24.3). Conclusions: Usage of an antibacterial envelope for neuromodulation has resulted in a lower infection rate at our center. Based on these results, we recommend the use of antimicrobial envelopes.

scholarly journals Maternal and Offspring Genetic Risk of Type 2 Diabetes and Offspring Birthweight Among African Ancestry Populations

2019 ◽  
Vol 104 (11) ◽  
pp. 5032-5042
Author(s):  
Mohammad L Rahman ◽  
Deepika Shrestha ◽  
Tsegaselassie Workalemahu ◽  
Jing Wu ◽  
Chunming Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cord Blood ◽  
Genetic Risk ◽  
Adverse Pregnancy Outcome ◽  
African Ancestry ◽  
Risk Scores ◽  
C Peptide ◽  
Glucose Levels ◽  
A Genome

Abstract Objectives Maternal genetic risk of type 2 diabetes (T2D) can influence offspring birthweight through shared offspring genetic risk and by altering intrauterine glycemic status. The aim of this study was to estimate the independent effects of maternal and offspring genetic risk scores (GRSs) of T2D on offspring birthweight and the extent to which intrauterine glycemic traits mediate the effect of maternal GRSs on offspring birthweight. Design The study involved 949 mother–offspring pairs of African ancestry from the Hyperglycemia Adverse Pregnancy Outcome study. GRSs of T2D were calculated separately for mothers and offspring as the weighted sum of 91 T2D risk alleles identified in a genome-wide association study meta-analysis in African Americans. Linear regression models were fit to estimate changes in birthweight by quartiles of GRSs. Mediation analysis was implemented to estimate the direct and indirect effects of maternal GRS on offspring birthweight through cord blood C-peptide and maternal fasting and postchallenge glucose levels. Results Maternal and offspring GRSs were independently and differentially associated with offspring birthweight. Changes (95% CI) in birthweight across increasing quartiles of maternal GRSs were 0 g (reference), 83.1 g (6.5, 159.6), 103.1 g (26.0, 180.2), and 92.7 g (12.6, 172.8) (P trend = 0.041) and those of offspring GRSs were 0 (reference), −92.0 g (−169.2, −14.9), −64.9 g (−142.4, 12.6), and 2.0 g (−77.8, 81.7) (P trend = 0.032). Cord blood C-peptide mediated the effect of maternal GRS on offspring birthweight, whereas maternal postchallenge glucose levels showed additive effects with maternal GRS on birthweight. Conclusions Maternal and offspring GRSs of T2D were independently and differentially associated with offspring birthweight.

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