scholarly journals Ancestry-Matched and Cross-Ancestry Genetic Risk Scores of Type 2 Diabetes in Pregnant Women and Fetal Growth—A Study in an Ancestrally Diverse Cohort

2021 ◽  
Author(s):  
Marion Ouidir ◽  
Xuehuo Zeng ◽  
Suvo Chatterjee ◽  
Cuilin Zhang ◽  
Fasil Tekola-Ayele
Keyword(s):  
Type 2 Diabetes ◽  
Birth Weight ◽  
Pregnant Women ◽  
Fetal Growth ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Challenge Test ◽  
Fetal Weight ◽  
Risk Scores

Maternal genetic variants associated with offspring birth weight and adult type 2 diabetes (T2D) risk loci show some overlap. Whether T2D genetic risk influences longitudinal fetal weight and the gestational timing when these relationships begin is unknown. We investigated the associations of T2D genetic risk score (GRS) with longitudinal fetal weight and birth weight among 1,513 pregnant women from four ancestral groups. Women had up to 5 ultrasonography. Ancestry-matched GRS were constructed separately using 380 European- (GRS<i>eur</i>), 104 African- (GRS<i>afr</i>), and 189 East Asian- (GRS<i>eas</i>) related T2D loci discovered in different population groups. Among European Americans, the highest quartile GRS<i>eur</i> was significantly associated with 53.8 g higher fetal weight (95% confidence interval [CI] 19.2-88.5 g) over the pregnancy. The associations began at gestational week 24 and continued through week 40, with a 106.8 g (95% CI: 6.5-207.1 g) increase in birth weight. The findings were similar in analysis further adjusted for maternal glucose challenge test results. No consistent association was found using ancestry-matched or cross-ancestry GRS in non-Europeans. In conclusion, T2D genetic susceptibility may influence fetal growth starting at mid-second trimester among Europeans. Absence of similar associations in non-Europeans urges the need for further genetic T2D studies in diverse ancestries.

scholarly journals Ancestry-Matched and Cross-Ancestry Genetic Risk Scores of Type 2 Diabetes in Pregnant Women and Fetal Growth - a Study in an Ancestrally Diverse Cohort

Diabetes ◽  
2021 ◽  
pp. db210655
Author(s):  
Marion Ouidir ◽  
Xuehuo Zeng ◽  
Suvo Chatterjee ◽  
Cuilin Zhang ◽  
Fasil Tekola-Ayele
Keyword(s):  
Type 2 Diabetes ◽  
Pregnant Women ◽  
Fetal Growth ◽  
Genetic Risk ◽  
Risk Scores ◽  
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 Autoimmunity plays a role in the onset of diabetes after 40 years of age

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 266-277 ◽  
Author(s):  
Olov Rolandsson ◽  
Christiane S. Hampe ◽  
Stephen J. Sharp ◽  
Eva Ardanaz ◽  
Heiner Boeing ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Incident Diabetes ◽  
Risk Scores ◽  
Antibody Positivity ◽  
Gad65 Antibody

Abstract Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

278-OR: Ancestry-Specific Genetic Risk Scores of Type 2 Diabetes and Longitudinal Fetal Growth in a Race-Ethnic Diverse Population

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 278-OR
Author(s):  
MARION OUIDIR ◽  
XUEHUO ZENG ◽  
SUVO CHATTERJEE ◽  
CUILIN ZHANG ◽  
FASIL TEKOLA-AYELE
Keyword(s):  
Type 2 Diabetes ◽  
Fetal Growth ◽  
Genetic Risk ◽  
Risk Scores ◽  
Diverse Population ◽  
Genetic Risk Scores

scholarly journals Type 2 Diabetes Genetic Risk Scores Are Associated With Increased Type 2 Diabetes Risk Among African Americans by Cardiometabolic Status

2018 ◽  
Vol 11 ◽  
pp. 117955141774894 ◽  
Author(s):  
Jill Layton ◽  
Xiaochen Li ◽  
Changyu Shen ◽  
Mary de Groot ◽  
Leslie Lange ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
African Americans ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Diabetes Risk ◽  
Risk Scores ◽  
Genetic Risk Scores ◽  
Normal Ranges ◽  
Increased Risk

The relationship between genetic risk variants associated with glucose homeostasis and type 2 diabetes risk has yet to be fully explored in African American populations. We pooled data from 4 prospective studies including 4622 African Americans to assess whether β-cell dysfunction (BCD) and/or insulin resistance (IR) genetic variants were associated with increased type 2 diabetes risk. The BCD genetic risk score (GRS) and combined BCD/IR GRS were significantly associated with increased type 2 diabetes risk. In cardiometabolic-stratified models, the BCD and IR GRS were associated with increased type 2 diabetes risk among 5 cardiometabolic strata: 3 clinically healthy strata and 2 clinically unhealthy strata. Genetic risk scores related to BCD and IR were associated with increased risk of type 2 diabetes in African Americans. Notably, the GRSs were significant predictors of type 2 diabetes among individuals in clinically normal ranges of cardiometabolic traits.

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

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.

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

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 ◽  
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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