scholarly journals Lower Dietary Intake of Plant Protein Is Associated with Genetic Risk of Diabetes-Related Traits in Urban Asian Indian Adults

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3064
Author(s):  
Sooad Alsulami ◽  
Dhanasekaran Bodhini ◽  
Vasudevan Sudha ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Rajendra Pradeepa ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Protein Intake ◽  
Asian Indians ◽  
Genetic Factors ◽  
Risk Allele ◽  
Plant Protein ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
The Impact ◽  
Lower Plant

The increasing prevalence of type 2 diabetes among South Asians is caused by a complex interplay between environmental and genetic factors. We aimed to examine the impact of dietary and genetic factors on metabolic traits in 1062 Asian Indians. Dietary assessment was performed using a validated semi-quantitative food frequency questionnaire. Seven single nucleotide polymorphisms (SNPs) from the Transcription factor 7-like 2 and fat mass and obesity-associated genes were used to construct two metabolic genetic risk scores (GRS): 7-SNP and 3-SNP GRSs. Both 7-SNP GRS and 3-SNP GRS were associated with a higher risk of T2D (p = 0.0000134 and 0.008, respectively). The 3-SNP GRS was associated with higher waist circumference (p = 0.010), fasting plasma glucose (FPG) (p = 0.002) and glycated haemoglobin (HbA1c) (p = 0.000066). There were significant interactions between 3-SNP GRS and protein intake (% of total energy intake) on FPG (Pinteraction = 0.011) and HbA1c (Pinteraction = 0.007), where among individuals with lower plant protein intake (<39 g/day) and those with >1 risk allele had higher FPG (p = 0.001) and HbA1c (p = 0.00006) than individuals with ≤1 risk allele. Our findings suggest that lower plant protein intake may be a contributor to the increased ethnic susceptibility to diabetes described in Asian Indians. Randomised clinical trials with increased plant protein in the diets of this population are needed to see whether the reduction of diabetes risk occurs in individuals with prediabetes.

scholarly journals Applicability of Obesity-Related SNPs and Their Effect Size Measures Defined on Populations with European Ancestry for Genetic Risk Estimation among Roma

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 516 ◽  
Author(s):  
Erand Llanaj ◽  
Péter Pikó ◽  
Károly Nagy ◽  
Gábor Rácz ◽  
Sándor János ◽  
...  
Keyword(s):  
Effect Size ◽  
Genetic Risk ◽  
Association Studies ◽  
Strong Association ◽  
European Ancestry ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Continuous Variables ◽  
Roma Population ◽  
The Impact

Investigations on the impact of genetic factors on the development of obesity have been limited regarding the Roma population—the largest and most vulnerable ethnic minority in Europe of Asian origin. Genetic variants identified from genetic association studies are primarily from European populations. With that in mind, we investigated the applicability of data on selected obesity-related single nucleotide polymorphisms (SNPs), obtained from the Hungarian general (HG) population of European origin, on the Hungarian Roma (HR) population. Twenty preselected SNPs in susceptible alleles, known to be significantly associated with obesity-related phenotypes, were used to estimate the effect of these SNPs on body mass index (BMI) and waist circumference (WC) in HG (N = 1783) and HR (N = 1225) populations. Single SNP associations were tested using linear and logistic regression models, adjusted for known covariates. Out of 20 SNPs, four located in FTO (rs1121980, rs1558902, rs9939609, and rs9941349) showed strong association with BMI and WC as continuous variables in both samples. Computations based on Adult Treatment Panel III (ATPIII) and the International Diabetes Federation’s (IDF) European and Asian criteria showed rs9941349 in FTO to be associated only with WC among both populations, and two SNPs (rs2867125, rs6548238) in TMEM18 associated with WC only in HG population. A substantial difference (both in direction and effect size) was observed only in the case of rs1801282 in PPARγ on WC as a continuous outcome. Findings suggest that genetic risk scores based on counting SNPs with relatively high effect sizes, defined based on populations with European ancestry, can sufficiently allow estimation of genetic susceptibility for Roma. Further studies are needed to clarify the role of SNP(s) with protective effect(s).

scholarly journals Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study

2018 ◽  
Vol 56 (9) ◽  
pp. 602-605 ◽  
Author(s):  
Andreas Beyerlein ◽  
Ezio Bonifacio ◽  
Kendra Vehik ◽  
Markus Hippich ◽  
Christiane Winkler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Clinical Type

BackgroundProgression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown.MethodsIn 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression.ResultsIslet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93).ConclusionsGenetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.

scholarly journals Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke

2019 ◽  
Vol 8 (3) ◽  
pp. 332 ◽  
Author(s):  
Chia-Shan Hsieh ◽  
Pang-Shuo Huang ◽  
Sheng-Nan Chang ◽  
Cho-Kai Wu ◽  
Juey-Jen Hwang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Signaling Pathway ◽  
Copy Number ◽  
Genetic Factors ◽  
Copy Number Variations ◽  
Nucleotide Polymorphisms ◽  
Thromboembolic Stroke ◽  
Genome Wide ◽  
A Genome ◽  
The Impact

Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-nucleotide polymorphisms in several genomic regions have been found to be associated with AF. However, these loci do not contribute to all the genetic risks of AF or AF related thromboembolic risks, suggesting that there are other genetic factors or variants not yet discovered. In the human genome, copy number variations (CNVs) could also contribute to disease susceptibility. In the present study, we sought to identify CNVs determining the AF-related thromboembolic risk. Using a genome-wide approach in 109 patients with AF and thromboembolic stroke and 14,666 controls from the Taiwanese general population (Taiwan Biobank), we first identified deletions in chromosomal regions 1p36.32-1p36.33, 5p15.33, 8q24.3 and 19p13.3 and amplifications in 14q11.2 that were significantly associated with AF-related stroke in the Taiwanese population. In these regions, 148 genes were involved, including several microRNAs and long non-recoding RNAs. Using a pathway analysis, we found deletions in GNB1, PRKCZ, and GNG7 genes related to the alpha-adrenergic receptor signaling pathway that play a major role in determining the risk of an AF-related stroke. In conclusion, CNVs may be genetic predictors of a risk of a thromboembolic stroke for patients with AF, possibly pointing to an impaired alpha-adrenergic signaling pathway in the mechanism of AF-related thromboembolism.

scholarly journals Testing Familial Transmission of Smoking With Two Different Research Designs

2017 ◽  
Vol 20 (7) ◽  
pp. 836-842 ◽  
Author(s):  
Jorien L Treur ◽  
Karin J H Verweij ◽  
Abdel Abdellaoui ◽  
Iryna O Fedko ◽  
Eveline L de Zeeuw ◽  
...  
Keyword(s):  
The Netherlands ◽  
Family Environment ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Environmental Influence ◽  
Smoking Initiation ◽  
Risk Scores ◽  
Environment Interaction ◽  
Polygenic Risk ◽  
Children Of Twins

Abstract Introduction Classical twin studies show that smoking is heritable. To determine if shared family environment plays a role in addition to genetic factors, and if they interact (G×E), we use a children-of-twins design. In a second sample, we measure genetic influence with polygenic risk scores (PRS) and environmental influence with a question on exposure to smoking during childhood. Methods Data on smoking initiation were available for 723 children of 712 twins from the Netherlands Twin Register (64.9% female, median birth year 1985). Children were grouped in ascending order of risk, based on smoking status and zygosity of their twin-parent and his/her co-twin: never smoking twin-parent with a never smoking co-twin; never smoking twin-parent with a smoking dizygotic co-twin; never smoking twin-parent with a smoking monozygotic co-twin; and smoking twin-parent with a smoking or never smoking co-twin. For 4072 participants from the Netherlands Twin Register (67.3% female, median birth year 1973), PRS for smoking were computed and smoking initiation, smoking heaviness, and exposure to smoking during childhood were available. Results Patterns of smoking initiation in the four group children-of-twins design suggested shared familial influences in addition to genetic factors. PRS for ever smoking were associated with smoking initiation in all individuals. PRS for smoking heaviness were associated with smoking heaviness in individuals exposed to smoking during childhood, but not in non-exposed individuals. Conclusions Shared family environment influences smoking, over and above genetic factors. Genetic risk of smoking heaviness was only important for individuals exposed to smoking during childhood, versus those not exposed (G×E). Implications This study adds to the very few existing children-of-twins (CoT) studies on smoking and combines a CoT design with a second research design that utilizes polygenic risk scores and data on exposure to smoking during childhood. The results show that shared family environment affects smoking behavior over and above genetic factors. There was also evidence for gene–environment interaction (G×E) such that genetic risk of heavy versus light smoking was only important for individuals who were also exposed to (second-hand) smoking during childhood. Together, these findings give additional incentive to recommending parents not to expose their children to cigarette smoking.

scholarly journals Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor

2014 ◽  
Vol 45 (1) ◽  
pp. 181-191 ◽  
Author(s):  
S. Walter ◽  
M. M. Glymour ◽  
K. Koenen ◽  
L. Liang ◽  
E. J. Tchetgen Tchetgen ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Conclusive Evidence ◽  
Anxiety Symptoms ◽  
Risk Scores ◽  
Health Study ◽  
Nucleotide Polymorphisms ◽  
Phobic Anxiety

BackgroundObesity and anxiety are often linked but the direction of effects is not clear.MethodUsing genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). ‘Functional’ GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS.ResultsIn observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women:β = 0.05, 95% confidence interval (CI) 0.030–0.068; men:β = 0.04, 95% CI 0.016–0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in theFTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms.ConclusionsOur findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particularFTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.

scholarly journals Genetic Risk Prediction of COVID-19 Susceptibility and Severity in the Indian Population

2021 ◽  
Vol 12 ◽  
Author(s):  
P. Prakrithi ◽  
Priya Lakra ◽  
Durai Sundar ◽  
Manav Kapoor ◽  
Mitali Mukerji ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Genetic Risk ◽  
Genome Wide Association Study ◽  
Risk Groups ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Genetic Risk Prediction ◽  
Indian Genome ◽  
Vaccine Distribution ◽  
Effective Public Health

Host genetic variants can determine their susceptibility to COVID-19 infection and severity as noted in a recent Genome-wide Association Study (GWAS). Given the prominent genetic differences in Indian sub-populations as well as differential prevalence of COVID-19, here, we compute genetic risk scores in diverse Indian sub-populations that may predict differences in the severity of COVID-19 outcomes. We utilized the top 100 most significantly associated single-nucleotide polymorphisms (SNPs) from a GWAS by Pairo-Castineira et al. determining the genetic susceptibility to severe COVID-19 infection, to compute population-wise polygenic risk scores (PRS) for populations represented in the Indian Genome Variation Consortium (IGVC) database. Using a generalized linear model accounting for confounding variables, we found that median PRS was significantly associated (p &lt; 2 x 10−16) with COVID-19 mortality in each district corresponding to the population studied and had the largest effect on mortality (regression coefficient = 10.25). As a control we repeated our analysis on randomly selected 100 non-associated SNPs several times and did not find significant association. Therefore, we conclude that genetic susceptibility may play a major role in determining the differences in COVID-19 outcomes and mortality across the Indian sub-continent. We suggest that combining PRS with other observed risk-factors in a Bayesian framework may provide a better prediction model for ascertaining high COVID-19 risk groups and to design more effective public health resource allocation and vaccine distribution schemes.

Abstract P215: Common Beta-cell-associated Genetic Variants and Hypertension or Anti-hypertensive Drugs do not Interact in Their Positive Associations With Risk for Rising Fasting Glucose or Incident Type 2 Diabetes in Framingham

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Jose M de Miguel-Yanes ◽  
Bianca Porneala ◽  
Michael J Pencina ◽  
Caroline S Fox ◽  
Jose C Florez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Genetic Risk ◽  
Risk Allele ◽  
Fasting Glucose ◽  
Beta Blockers ◽  
Risk Scores ◽  
Joint Models ◽  
Interaction Terms

Background: Hypertension (HTN) and some anti-HTN drugs raise fasting glucose (FG) levels and type 2 diabetes (T2D) risk. We hypothesized that common single nucleotide polymorphisms (SNPs) associated with FG or T2D that influence beta-cell function will interact with hypertension (HTN) or anti-HTN drugs in their positive associations with change over time in FG (ΔFG) or incident T2D. Methods: We studied 3,471 Framingham Offspring Study participants comprising 18,786 person-exams (mean age 49 yr; 54% women), in pooled (7 ∼4-yr periods) age-, sex-adjusted logistic regression models predicting T2D incidence, or age-, sex-, baseline FG-adjusted mixed linear models testing ΔFG (FG end minus beginning of period). T2D cases were excluded at baseline of each period, and people who started T2D treatment within a given period were removed for ΔFG analyses. We defined three HTN exposures: 1) HTN (SBP≥140/DBP≥90 mmHg) vs. no-HTN; 2) treated vs. untreated HTN; 3) five mutually-exclusive anti-HTN drug categories (beta-blockers, thiazides, renin-angiotensin system agents, combination, other) vs. untreated HTN, and two genetic exposures reflecting total beta-cell genetic risk burden: 16 FG-SNP and 33 T2D-SNP (only 8 overlap) additive genetic risk scores. We tested ∼4-year mean ΔFG and odds of T2D by HTN category and per-risk allele change in SNP scores, seeking first-order HTNxSNP significant interaction (P<0.05). Results: Versus no HTN, HTN (n=5,372 p-e) was associated with higher ∼4-year ΔFG (0.14 vs. 0.03 mmol/l; P<0.0001) and ∼3-fold increased odds of T2D (OR 3.3; P<0.0001). Versus untreated HTN, treated HTN (n=2,832 p-e) conferred higher ΔFG (0.18 vs. 0.12 mmol/l; P<0.0001) and 1.5-fold increased odds of T2D (P=0.0006). Versus untreated HTN, beta-blockers (n=676 p-e; OR=1.58), combined (n=499 p-e; OR=1.57) and other (n=569 p-e; OR=1.94) were associated with increased odds of T2D (all P<0.03). Per-SNP score risk allele, ΔFG increased by 0.03 mmol/l (P=2.2x10 −16 ) and odds of T2D increased 17% (P=3.1x10 −08 ). In joint models with interaction terms, all HTN-treatment category-by-SNP score interaction terms were non-significant. In joint models without interaction, HTN (P<0.0001) and HTN treatment (P<0.02), but no specific drugs (all but one P>0.02), and per FG-SNP or T2D-SNP risk allele (highest P value=0.0005), all independently predicted ΔFG or incident T2D. Conclusion: HTN, HTN treatment and common FG- and T2D-SNP genetic scores were independently associated with ΔFG and T2D incidence, but did not modify each other's association with ΔFG or T2D risk. Next, larger samples and individual SNP-by-specific drug category interaction tests might disclose some biological basis for T2D risk associated with anti-HTN therapy.

Abstract 500: Assessing the Impact of Cardiovascular Disease-Related Genetic Variation on Clinical Cognitive Impairment

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Joseph B Dube ◽  
Christopher T Johansen ◽  
John Robinson ◽  
Joan Lindsay ◽  
Vladimir Hachinski ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Genetic Variation ◽  
Cognitive Impairment ◽  
Genetic Markers ◽  
Vascular Dysfunction ◽  
Risk Scores ◽  
Study Cohort ◽  
Nucleotide Polymorphisms ◽  
Apoe Ε4 ◽  
The Impact

Introduction: “Cognitive impairment, no dementia” (CIND) is a prodromal stage of cognitive decline which marks the onset of dementia and is due most commonly to 1) Alzheimer disease (AD) or 2) vascular dysfunction. In order to assess the genetic component of CIND susceptibility, we investigated cardiovascular disease (CVD) and AD-associated genetic variation in CIND patients, hypothesizing that the genetic variation affecting CVD and AD susceptibility is also associated with CIND susceptibility. Methods: Our study cohort was taken from the Canadian Study of Health and Aging (CSHA) and was comprised of patients >65 years old with CIND (n=274) and matched normal controls (n=301). We genotyped ∼200,000 CVD-related SNPs using the Cardio-Metabochip genotyping array (Illumina). We also genotyped a panel of the top 11 AD-associated single nucleotide polymorphisms (SNPs) and APOE isotype. We tested for association between CIND status and genotypes using a logistic regression model adjusted for appropriate covariates. Genetic risk scores (GRSs) evaluated associations between CIND status and the accumulation of multiple genetic markers. Results: From our Cardio-Metabochip analysis, we identified 5 novel CIND susceptibility loci, with rs16901621 in FLJ22536 as our most significantly associated SNP (P=1.05E-06, OR=2.51, 95%CI=1.73-3.63). APOE ε4 isotype was modestly associated with CIND status (P<0.05), while AD SNP risk alleles were not associated (P>0.1). Conclusion: Using a high-throughput CVD microarray, we found novel genetic markers for CIND approaching genome-wide levels of significance. In contrast, known genetic markers for AD, such as APOE ε4 showed only modest associations in this cohort. Follow-up of variants in a CSHA replication cohort (n=370) is currently underway.

The impact of sex, age at onset, recurrence, mode of ascertainment and medical complications on the family genetic risk score profiles for alcohol use disorder

2021 ◽  
pp. 1-9
Author(s):  
Kenneth S. Kendler ◽  
Henrik Ohlsson ◽  
Jan Sundquist ◽  
Kristina Sundquist
Keyword(s):  
Alcohol Use ◽  
Genetic Risk ◽  
Criminal Behavior ◽  
Alcohol Use Disorder ◽  
Genetic Risk Score ◽  
Age At Onset ◽  
Risk Scores ◽  
Medical Complications ◽  
The Family ◽  
The Impact

Abstract Background Alcohol use disorder (AUD) is clinically heterogeneous. We examine its potential genetic heterogeneity as a function of sex, age, clinical features and mode of ascertainment. Methods In the Swedish population born 1932–1995 (n = 5 829 952), we examined the genetic risk profiles for AUD, major depression (MD), anxiety disorders, bipolar disorder, drug use disorder (DUD), attention deficit-hyperactivity disorder (ADHD) and criminal behavior (CB) in 361 124 cases of AUD subdivided by sex, age at onset (AAO), recurrence, mode of ascertainment and medical complications. Family genetic risk scores (FGRS), calculated from 1st to 5th-degree relatives controlling of cohabitation, assesses genetic risk from phenotypes in the family, not from DNA variants. Results FGRS profiles differed modestly across sex with all scores higher in females. Differences were more pronounced for AAO and recurrence with the FGRS for AUD, DUD, ADHD and CB substantially higher in cases with early AAO or high recurrence rates. Genetic profiles differed considerably by mode of ascertainment, with higher FGRS for AUD and most other disorders in patients seen in hospital v. primary care settings. Cases of AUD with medical complications had higher FGRS for AUD. AUD cases comorbid with MD and DUD had higher FGRS risk for AUD, but this genetic may be less specific given increases in FGRS for multiple other disorders. Conclusions From a genetic perspective, AUD differs substantially as a function of AAO, recurrence, mode of ascertainment and patterns of comorbidity, suggesting caution in cross-sample comparisons of AUD cohorts that differ in these features.

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