scholarly journals Interactions between Polygenic Risk Scores, Dietary Pattern, and Menarche Age with the Obesity Risk in a Large Hospital-Based Cohort

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3772
Author(s):  
Sunmin Park ◽  
Hye Jeong Yang ◽  
Min Jung Kim ◽  
Haeng Jeon Hur ◽  
Soon-Hee Kim ◽  
...  
Keyword(s):  
Food Intake ◽  
Genetic Variants ◽  
Risk Scores ◽  
City Hospital ◽  
Obesity Risk ◽  
Fried Food ◽  
A Genome ◽  
Fried Foods ◽  
Menarche Age ◽  
High Bmi

Obese Asians are more susceptible to metabolic diseases than obese Caucasians of the same body mass index (BMI). We hypothesized that the genetic variants associated with obesity risk interact with the lifestyles of middle-aged and elderly adults, possibly allowing the development of personalized interventions based on genotype. We aimed to examine this hypothesis in a large city hospital-based cohort in Korea. The participants with cancers, thyroid diseases, chronic kidney disease, or brain-related diseases were excluded. The participants were divided into case and control according to their BMI: ≥25 kg/m2 (case; n = 17,545) and <25 kg/m2 (control; n = 36,283). The genetic variants that affected obesity risk were selected using a genome-wide association study, and the genetic variants that interacted with each other were identified by generalized multifactor dimensionality reduction analysis. The selected genetic variants were confirmed in the Ansan/Ansung cohort, and polygenetic risk scores (PRS)−nutrient interactions for obesity risk were determined. A high BMI was associated with a high-fat mass (odds ratio (OR) = 20.71) and a high skeletal muscle-mass index (OR = 3.38). A high BMI was positively related to metabolic syndrome and its components, including lipid profiles, whereas the initial menstruation age was inversely associated with a high BMI (OR = 0.78). The best model with 5-SNPs included SEC16B_rs543874, DNAJC27_rs713586, BDNF_rs6265, MC4R_rs6567160, and GIPR_rs1444988703. The high PRS with the 5-SNP model was positively associated with an obesity risk of 1.629 (1.475–1.798) after adjusting for the covariates. The 5-SNP model interacted with the initial menstruation age, fried foods, and plant-based diet for BMI risk. The participants with a high PRS also had a higher obesity risk when combined with early menarche, low plant-based diet, and a high fried-food intake than in participants with late menarche, high plant-based diet, and low fried-food intake. In conclusion, people with a high PRS and earlier menarche age are recommended to consume fewer fried foods and a more plant-based diet to decrease obesity risk. This result can be applied to personalized nutrition for preventing obesity.

scholarly journals HUMAN LONGEVITY IS INFLUENCED BY MANY GENETIC VARIANTS: EVIDENCE FROM 75,000 UK BIOBANK PARTICIPANTS

2016 ◽  
Author(s):  
Luke C Pilling ◽  
Janice L Atkins ◽  
Kirsty Bowman ◽  
Samuel E Jones ◽  
Jessica Tyrrell ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Paternal Age ◽  
Risk Scores ◽  
Human Longevity ◽  
Uk Biobank ◽  
Age At Death ◽  
Genetic Risk Scores ◽  
A Genome

Variation in human lifespan is 20 to 30% heritable but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. Genotyped variants (n=845,997) explained 10.2% (SD=1.3%) of combined parental longevity. In GWAS, a locus in the nicotine receptor CHRNA3 - previously associated with increased smoking and lung cancer - was associated with paternal age at death, with each protective allele (rs1051730[G]) being associated with 0.03 years later age at father's death (p=3x10-8). Offspring of longer lived parents had more protective alleles (lower genetic risk scores) for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer's disease. In candidate gene analyses, variants in the TOMM40/APOE locus were associated with longevity (including rs429358, p=3x10-5), but FOXO variants were not associated. These results support a multiple protective factors model for achieving longer lifespans in humans, with a prominent role for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable.

scholarly journals The correlation of obesity, smoking, fried foods consumption pattern and food intake with lipid profile in civil servant in Yogyakarta, Indonesia

2017 ◽  
Vol 4 (3) ◽  
pp. 690 ◽  
Author(s):  
Toto Sudargo ◽  
Fahmi Tiara Sari ◽  
Novita Dian Naomi
Keyword(s):  
Food Intake ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
Food Consumption ◽  
Total Cholesterol Level ◽  
Civil Servant ◽  
Consumption Pattern ◽  
Fat Intake ◽  
Fried Food ◽  
Fried Foods

Background: Dyslipidemia is an abnormal change in the levels of lipid profile such as increased levels of total cholesterol, LDL, triglycerides or decreased levels of HDL. The proportion of the Indonesian population (> 15 years old) with a total cholesterol level above the normal value amounted to 35,9%.  Objective: To determine the correlation of obesity, smoking, fried food consumption pattern and food intake with lipid profile in civil servant in Yogyakarta.Methods: This study is an observational study with cross sectional design at employees of Gadjah Mada University who perform medical check-up at the GMC-Health Center Yogyakarta. There are 179 respondents in the study.  Subjects are categorized to have dyslipidemia (based on NCEP ATP III criteria) if it meets ≥ 1 of the following criteria: (1) Total cholesterol ≥ 200 mg/dL; (2) LDL cholesterol ≥ 130 mg / dL; (3) HDL cholesterol < 40 mg / dL; and (4) Triglycerides ≥150 mg / dL. Fried food consumption patterns and food intake is obtained using semi-quantitative food frequency questionnaire (SQ-FFQ). Data were analyzed by Chi Square, Independent t test and Mann Whitney test (adjusted for scale variables used) with a confidence level of 95%.Results: One hundred and fifty five of 179 respondents (87.3%) diagnosed with dyslipidemia. There are 52% abnormal cholesterol, abnormal LDL 67%, 43% and 28.5% with abnormal HDL and abnormal triglycerides, respectively. The statistical test showed the correlation of obesity (p=0,022), smoking (p=0,013), the type of fried food (p=0.047), the amount of fried foods (p=0,013) and fat intake from fried foods (p=0.036) has significant association with lipid profile levels.Conclusions: There is significant correlation between obesity, smoking, type of fried food, amount of fried foods and fat intake from fried food with lipid profile levels.

scholarly journals Effects of single genetic variants and polygenic obesity risk scores on disordered eating in adolescents – The HUNT study

Appetite ◽  
2017 ◽  
Vol 118 ◽  
pp. 8-16 ◽  
Author(s):  
Farzaneh Saeedzadeh Sardahaee ◽  
Turid Lingaas Holmen ◽  
Nadia Micali ◽  
Kirsti Kvaløy
Keyword(s):  
Disordered Eating ◽  
Genetic Variants ◽  
Risk Scores ◽  
Obesity Risk ◽  
Hunt Study ◽  
Polygenic Obesity

scholarly journals Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yong-Fei Wang ◽  
Yan Zhang ◽  
Zhiming Lin ◽  
Huoru Zhang ◽  
Ting-You Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Age Of Onset ◽  
Treatment Options ◽  
Human Leukocyte ◽  
Risk Scores ◽  
Systemic Lupus ◽  
Disease Manifestation ◽  
A Genome

AbstractSystemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.

scholarly journals Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
José Jaime Martínez-Magaña ◽  
Alma Delia Genis-Mendoza ◽  
Jorge Ameth Villatoro Velázquez ◽  
Marycarmen Bustos-Gamiño ◽  
Isela Esther Juárez-Rojop ◽  
...  
Keyword(s):  
Substance Use ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Logistic Models ◽  
Genome Wide Association ◽  
Risk Scores ◽  
Multinomial Models ◽  
Gamma Receptor ◽  
Genome Wide ◽  
A Genome

AbstractThe combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e−05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.

Has the time come to integrate genetic risk scores into clinical practice?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F.V Moniz Mendonca ◽  
M.I Mendonca ◽  
A Pereira ◽  
J Monteiro ◽  
J Sousa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Practice ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Risk Scores ◽  
Cumulative Number ◽  
Genetic Risk Scores ◽  
Risk Alleles ◽  
Cad Risk

Abstract Background The risk for Coronary Artery Disease (CAD) is determined by both genetic and environmental factors, as well as by the interaction between them. It is estimated that genetic factors could account for 40% to 55% of the existing variability among the population (inheritability). Therefore, some authors have advised that it is time we integrated genetic risk scores into clinical practice. Aim The aim of this study was to evaluate the magnitude of the association between an additive genetic risk score (aGRS) and CAD based on the cumulative number of risk alleles in these variants, and to estimate whether their use is valuable in clinical practice. Methods A case-control study was performed in a Portuguese population. We enrolled 3120 participants, of whom 1687 were CAD patients and 1433 were normal controls. Controls were paired to cases with respect to gender and age. 33 genetic variants known to be associated with CAD were selected, and an aGRS was calculated for each individual. The aGRS was further subdivided into deciles groups, in order to estimate the CAD risk in each decile, defined by the number of risk alleles. The magnitude of the risk (odds ratio) was calculated for each group by multiple logistic regression using the 5th decile as the reference group (median). In order to evaluate the ability of the aGRS to discriminate susceptibility to CAD, two genetic models were performed, the first with traditional risk factors (TRF) and second with TRF plus aGRS. The AUC of the two ROC curves was calculated. Results A higher prevalence of cases over controls became apparent from the 6th decile of the aGRS, reflecting the higher number of risk alleles present (see figure). The difference in CAD risk was only significant from the 6th decile, increasing gradually until the 10th decile. The odds ratio (OR) for the last decile related to 5th decile (median) was 1.87 (95% CI:1.36–2.56; p&lt;0.0001). The first model yielded an AUC=0.738 (95% CI:0.720–0.755) and the second model was slightly more discriminative for CAD risk (AUC=0.748; 95% CI:0.730–0.765). The DeLong test was significant (p=0.0002). Conclusion Adding an aGRS to the non-genetic risk factors resulted in a modest improvement in the ability to discriminate the risk of CAD. Such improvement, even if statistically significant, does not appear to be of real value in clinical practice yet. We anticipate that with the development of further knowledge about different SNPs and their complex interactions, and with the inclusion of rare genetic variants, genetic risk scores will be better suited for use in a clinical setting. Funding Acknowledgement Type of funding source: None

scholarly journals Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1940
Author(s):  
Karl Michaëlsson ◽  
Susanna C. Larsson
Keyword(s):  
Bone Mineral Density ◽  
Confidence Interval ◽  
Bone Mineral ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Alpha Tocopherol ◽  
European Ancestry ◽  
Mineral Density ◽  
Standard Deviation Increase ◽  
A Genome

Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10−8 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm2 increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.

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