Dataset Information

Polygenetic-Risk Scores for A Glaucoma Risk Interact with Blood Pressure, Glucose Control, and Carbohydrate Intake.

ABSTRACT: Glaucoma, a leading cause of blindness, has multifactorial causes, including environmental and genetic factors. We evaluated genetic risk factors of glaucoma with gene-gene interaction and explored modifications of genetic risk with gene-lifestyles interaction in adults >40 years. The present study included 377 subjects with glaucoma and 47,820 subjects without glaucoma in a large-scale hospital-based cohort study from 2004 to 2013. The presence of glaucoma was evaluated by a diagnostic questionnaire evaluated by a doctor. The genome-wide association study was performed to identify genetic variants associated with glaucoma risk. Food intake was assessed using a semiquantitative food frequency questionnaire. We performed generalized multifactor dimensionality reduction analysis to construct polygenetic-risk score (PRS) and explored gene × nutrient interaction. PRS of the best model included LIM-domain binding protein-2 (LDB2) rs3763969, cyclin-dependent kinase inhibitor 2B (CDKN2B) rs523096, ABO rs2073823, phosphodiesterase-3A (PDE3A) rs12314390, and cadherin 13 (CDH13) rs12449180. Glaucoma risk in the high-PRS group was 3.02 times that in the low-PRS group after adjusting for confounding variables. For those with low serum glucose levels (<126 mg/dL), but not for those with high serum glucose levels, glaucoma risk in the high-PRS group was 3.16 times that in the low-PRS group. In those with high carbohydrate intakes (?70%), but not in those with low carbohydrate intakes, glaucoma risk was 3.74 times higher in the high-PRS group than in the low-PRS group. The glaucoma risk was 3.87 times higher in the high-PRS group than in the low-PRS group only in a low balanced diet intake. In conclusion, glaucoma risk increased by three-fold in adults with a high PRS, and it can be reduced by good control of serum glucose concentrations and blood pressure (BP) with a balanced diet intake. These results can be applied to precision nutrition to reduce glaucoma risk.

SUBMITTER: Jee D

PROVIDER: S-EPMC7693735 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Polygenetic-Risk Scores for A Glaucoma Risk Interact with Blood Pressure, Glucose Control, and Carbohydrate Intake.

Jee Donghyun D Huang ShaoKai S Kang Suna S Park Sunmin S

Nutrients 20201026 11

Glaucoma, a leading cause of blindness, has multifactorial causes, including environmental and genetic factors. We evaluated genetic risk factors of glaucoma with gene-gene interaction and explored modifications of genetic risk with gene-lifestyles interaction in adults >40 years. The present study included 377 subjects with glaucoma and 47,820 subjects without glaucoma in a large-scale hospital-based cohort study from 2004 to 2013. The presence of glaucoma was evaluated by a diagnostic question ...[more]

PMID: 33114701

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Project description:Age-related cataract (ARC) development is associated with loss of crystalline lens transparency related to interactions between genetic and environmental factors. We hypothesized that polygenetic risk scores (PRS) of the selected genetic variants among the ARC-related genes might reveal significant genetic impacts on ARC risk, and the PRS might have gene-gene and gene-lifestyle interactions. We examined the hypothesis in 1972 and 39,095 subjects aged ?50 years with and without ARC, respectively, in a large-scale hospital-based cohort study conducted from 2004 to 2013. Single nucleotide polymorphisms (SNPs) of the genes related to ARC risk were identified, and polygenetic risk scores (PRS) were generated based on the results of a generalized multifactor dimensionality reduction analysis. Lifestyle interactions with PRS were evaluated. The PRS derived from the best model included the following six SNPs related to crystallin metabolism: ULK4_rs1417380362, CRYAB_rs2070894, ACCN1_rs55785344, SSTR2_rs879419608, PTN_rs322348, and ICA1_rs200053781. The risk of ARC in the high-PRS group was 2.47-fold higher than in the low-PRS group after adjusting for confounders. Age, blood pressure, and glycemia interacted with PRS to influence the risk of ARC: the incidence of ARC was much higher in the elderly (?65 years) and individuals with hypertension or hyperglycemia. The impact of PRS on ARC risk was greatest in middle-aged individuals with hypertension or hyperglycemia. Na, coffee, and a Western-style diet intake also interacted with PRS to influence ARC risk. ARC risk was higher in the high-PRS group than in the low-PRS group, and high Na intake, Western-style diet, and low coffee intake elevated its risk. In conclusion, ARC risk had a positive association with PRS related to crystallin metabolism. The genetic impact was greatest among those with high Na intake or hypertension. These results can be applied to precision nutrition interventions to prevent ARC.

Project description:The incidence of thyroid cancer continues to increase steadily, and this increasing incidence cannot be attributed solely to the overdiagnosis of microcarcinoma or technical advancements in detection methods and may also depend on environmental and genetic factors. However, the impacts and interactions of genetic and environmental factors remain controversial, and they may differ in Eastern and Western countries. The study's purpose was to identify single nucleotide polymorphisms of genes related to cell differentiation and inflammation to influence thyroid cancer incidence and determine interactions with lifestyles in a large city hospital-based cohort. Genetic variants were selected by genome-wide association study with thyroid cancer participants (case; n = 495) and controls without cancers (n = 56,439). SNPs having gene-gene interactions were selected by generalized multifactor dimensionality reduction. Polygenic risk scores (PRSs) were generated by summing the number of selected SNP risk alleles. PRSs of the best model included 6 SNPs, that is, DIRC3_rs6759952, GAP43_rs13059137, NRG1_rs7834206, PROM1_rs72616195, LRP1B_rs1369535, and LOC100507065_rs11175834. Participants with a high-PRS had a higher thyroid cancer risk by 3.9-fold than those with a low-PRS. The following variables were related to an increased thyroid cancer risk; female (OR = 4.21), high white blood cell count (OR = 4.03), and high energy (OR = 7.00), low alcohol (OR = 4.11), and high seaweed (OR = 4.02) intakes. These variables also interacted with PRS to influence thyroid cancer risk. Meat/noodle diet patterns interacted with PRSs to increase thyroid cancer risk (p = 0.0023). In conclusion, women with a high-PRS associated with cell differentiation and inflammation were at an elevated thyroid cancer risk. Daily energy, seaweeds, and alcohol intake interacted with PRS for thyroid cancer risk. These results could be applied to personalized nutrition plans to reduce the risk of thyroid cancer.

Project description:BackgroundsEarly menstruation, late menopause, no pregnancy, and genetic factors are known risk factors of the disease, but their effects may differ in Asian and Caucasian women. The purpose of this study was to identify genetic variants of genes related to estrogen signaling in a large city hospital-based cohort and to determine their interactions with lifestyles.MethodsThis is a case-control study. Three hundred ninety participants diagnosed with breast cancer were compared with 36,290 controls(no cancer)to explore the genetic variants to influence breast cancer risk. Based on GWAS results, the selected genetic variants were subjected to their interactions by generalized multifactor dimensionality reduction (GMDR) analysis.ResultsEarly menstruation(OR=1.55), early menopause (OR=1.70), and no experience of pregnancy(OR=2.86) had a positive association with breast cancer risk(P<0.05). The selected polygenetic risk score(PRS) models included four SNPs and seven SNPs: The four-SNP PRS model included CDH13_rs12600325, SMYD3_rs3753686, FGF12_rs2134635, and ESRRB_rs10873289, and in the seven-SNP PRS model, ESR1_ rs2046210, estrogen-related receptor gamma(ESRRG)_rs17043393, and EGFR_ rs6958497 were added into the four-SNP PRS model. Early menstruation, early menopause, and no pregnancy experience interacted with four-SNP PRS. For the participants who had early menstruation and early menopause, high-PRS had an association with a much higher breast cancer risk than the low-PRS in the four-SNP model. However, metabolic parameters, nutrient intakes, and different dietary patterns did not interact with PRS for breast cancer risk. However, alcohol intake interacted with PRS for breast cancer risk (OR=2.33 and 8.07 for mild and moderate alcohol consumption, respectively; P=0.0004).ConclusionConsideration of age at menarche and menopause, pregnancy experience, and alcohol intake may be required to reduce breast cancer risk in women with a high-PRS of genes related to the estrogen signaling pathway.

Project description:Graves's disease and thyroiditis induce hyperthyroidism, the causes of which remain unclear, although they are involved with genetic and environmental factors. We aimed to evaluate polygenetic variants for hyperthyroidism risk and their interaction with metabolic parameters and nutritional intakes in an urban hospital-based cohort. A genome-wide association study (GWAS) of participants with (cases; n = 842) and without (controls, n = 38,799) hyperthyroidism was used to identify and select genetic variants. In clinical and lifestyle interaction with PRS, 312 participants cured of hyperthyroidism were excluded. Single nucleotide polymorphisms (SNPs) associated with gene-gene interactions were selected by hyperthyroidism generalized multifactor dimensionality reduction. Polygenic risk scores (PRSs) were generated by summing the numbers of selected SNP risk alleles. The best gene-gene interaction model included tumor-necrosis factor (TNF)_rs1800610, mucin 22 (MUC22)_rs1304322089, tribbles pseudokinase 2 (TRIB2)_rs1881145, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)_rs231775, lipoma-preferred partner (LPP)_rs6780858, and human leukocyte antigen (HLA)-J_ rs767861647. The PRS of the best model was positively associated with hyperthyroidism risk by 1.939-fold (1.317-2.854) after adjusting for covariates. PRSs interacted with age, metabolic syndrome, and dietary inflammatory index (DII), while hyperthyroidism risk interacted with energy, calcium, seaweed, milk, and coffee intake (P < 0.05). The PRS impact on hyperthyroidism risk was observed in younger (<55 years) participants and adults without metabolic syndrome. PRSs were positively associated with hyperthyroidism risk in participants with low dietary intakes of energy (OR = 2.74), calcium (OR = 2.84), seaweed (OR = 3.43), milk (OR = 2.91), coffee (OR = 2.44), and DII (OR = 3.45). In conclusion, adults with high PRS involved in inflammation and immunity had a high hyperthyroidism risk exacerbated under low intakes of energy, calcium, seaweed, milk, or coffee. These results can be applied to personalized nutrition in a clinical setting.

Project description:Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Participants were divided into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted predisposition for OCD, SCZ, cross-disorder, and CLZ/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabolism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6% and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in years (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant correlation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ, CLZ/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment duration in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS/OCD. Limitations attributed to the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ plasma level, is relevant for OCD development.

Dataset Information

Polygenetic-Risk Scores for A Glaucoma Risk Interact with Blood Pressure, Glucose Control, and Carbohydrate Intake.

Publications

Polygenetic-Risk Scores for A Glaucoma Risk Interact with Blood Pressure, Glucose Control, and Carbohydrate Intake.

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