Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose-Insulin Homeostasis in Youth: The Exploring Perinatal Outcomes Among Children (EPOCH) Study

Objective: The metabolic phenotype of youth-onset type 2 diabetes (T2D) differs from that of adult-onset T2D, but little is known about genetic contributions. We aimed to evaluate the association between a T2D genetic risk score (GRS) and traits related to glucose-insulin homeostasis among healthy youth. Research Design and Methods: We used data from 356 youth (mean age 16.7 years, 50% female) in the EPOCH cohort to calculate a standardized weighted GRS based on 271 single nucleotide polymorphisms (SNPs) associated with T2D in adults. We used linear regression to assess associations of the GRS with log-transformed fasting glucose, 2-hour glucose, homeostasis model of insulin resistance (HOMA-IR), oral disposition index, and insulinogenic index adjusted for age, sex, body mass index (BMI) z-score, in utero exposure to maternal diabetes, and genetic principal components. We also evaluated effect modification by BMI z-score, in utero exposure to maternal diabetes and ethnicity. Results: Higher weighted GRS was associated with lower oral disposition index (b=-0.11; 95% CI: -0.19, -0.02) and insulinogenic index (b=-0.08; 95% CI: -0.17, -0.001), but not with fasting glucose (b=0.01; 95% CI: -0.01, 0.02), 2-hour glucose (b=0.03; 95% CI: -0.0004, 0.06), or HOMA-IR (b=0.02; 95% CI: -0.04, 0.07). BMI z-score and in utero exposure to maternal diabetes increased the effect of the GRS on glucose levels. Conclusions: Our results suggest that T2D genetic risk factors established in adults are relevant to glucose-insulin homeostasis in youth and that maintaining a healthy weight may be particularly important for youth with high genetic risk for T2D.

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Interaction between dietary branched-chain amino acids and genetic risk score on the risk of type 2 diabetes in Chinese

Genes & Nutrition ◽

10.1186/s12263-021-00684-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Weiqi Wang ◽

Haiyang Jiang ◽

Ziwei Zhang ◽

Wei Duan ◽

Tianshu Han ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Predisposition ◽

Genetic Risk ◽

Odds Ratio ◽

Regression Models ◽

Fasting Glucose ◽

Genetic Risk Score ◽

Branched Chain Amino Acids ◽

Branched Chain

Abstract Background and objectives Previous studies have found the important gene-diet interactions on type 2 diabetes (T2D) incident but have not followed branched-chain amino acids (BCAAs), even though they have shown heterogeneous effectiveness in diabetes-related factors. So in this study, we aim to investigate whether dietary BCAAs interact with the genetic predisposition in relation to T2D risk and fasting glucose in Chinese adults. Methods In a case-control study nested in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases, we obtained data for 434 incident T2D cases and 434 controls matched by age and sex. An unweighted genetic risk score (GRS) was calculated for 25 T2D-related single nucleotide polymorphisms by summation of the number of risk alleles for T2D. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and fasting glucose. Results Significant interactions were found between GRS and dietary BCAAs on T2D risk and fasting glucose (p for interaction = 0.001 and 0.004, respectively). Comparing with low GRS, the odds ratio of T2D in high GRS were 2.98 (95% CI 1.54–5.76) among those with the highest tertile of total BCAA intake but were non-significant among those with the lowest intake, corresponding to 0.39 (0.12) mmol/L versus − 0.07 (0.10) mmol/L fasting glucose elevation per tertile. Viewed differently, comparing extreme tertiles of dietary BCAAs, the odds ratio (95% CIs) of T2D risk were 0.46 (0.22–0.95), 2.22 (1.15–4.31), and 2.90 (1.54–5.47) (fasting glucose elevation per tertile: − 0.23 (0.10), 0.18 (0.10), and 0.26 (0.13) mmol/L) among participants with low, intermediate, and high genetic risk, respectively. Conclusions This study indicated that dietary BCAAs could amplify the genetic association with T2D risk and fasting glucose. Moreover, higher BCAA intake showed positive association with T2D when genetic predisposition was also high but changed to negative when genetic predisposition was low.

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Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose-Insulin Homeostasis in Youth: The Exploring Perinatal Outcomes Among Children (EPOCH) Study

Diabetes Care ◽

10.2337/dc21-0464 ◽

2021 ◽

pp. dc210464

Author(s):

Maggie A. Stanislawski ◽

Elizabeth Litkowski ◽

Sridharan Raghavan ◽

Kylie K. Harrall ◽

Jessica Shaw ◽

...

Keyword(s):

Type 2 Diabetes ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Perinatal Outcomes ◽

Insulin Homeostasis

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Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress

Scientific Reports ◽

10.1038/s41598-018-26106-z ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 3

Author(s):

Minjoo Kim ◽

Minkyung Kim ◽

Limin Huang ◽

Sun Ha Jee ◽

Jong Ho Lee

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Risk Score ◽

Genetic Variants ◽

Genetic Risk ◽

Fasting Glucose ◽

Genetic Risk Score ◽

Newly Diagnosed ◽

Common Genetic Variants

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

Genes ◽

10.3390/genes10110942 ◽

2019 ◽

Vol 10 (11) ◽

pp. 942 ◽

Cited By ~ 7

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.

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