scholarly journals Prioritizing individual genetic variants after kernel machine testing using variable selection

2016 ◽  
Vol 40 (8) ◽  
pp. 722-731 ◽  
Author(s):  
Qianchuan He ◽  
Tianxi Cai ◽  
Yang Liu ◽  
Ni Zhao ◽  
Quaker E. Harmon ◽  
...  
Keyword(s):  
Variable Selection ◽  
Genetic Variants ◽  
Kernel Machine

scholarly journals Associating Multivariate Quantitative Phenotypes with Genetic Variants in Family Samples with a Novel Kernel Machine Regression Method

Genetics ◽  
2015 ◽  
Vol 201 (4) ◽  
pp. 1329-1339 ◽  
Author(s):  
Qi Yan ◽  
Daniel E. Weeks ◽  
Juan C. Celedón ◽  
Hemant K. Tiwari ◽  
Bingshan Li ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Regression Method ◽  
Kernel Machine ◽  
Kernel Machine Regression

scholarly journals Bayesian variable selection with a pleiotropic loss function in Mendelian randomization

2019 ◽  
Author(s):  
Apostolos Gkatzionis ◽  
Stephen Burgess ◽  
David V Conti ◽  
Paul J Newcombe
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
Variable Selection ◽  
Diastolic Blood Pressure ◽  
Loss Function ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Bayesian Variable Selection

AbstractMendelian randomization is the use of genetic variants as instruments to assess the existence of a causal relationship between a risk factor and an outcome. A Mendelian randomization analysis requires a set of genetic variants that are strongly associated with the risk factor and only associated with the outcome through their effect on the risk factor. We describe a novel variable selection algorithm for Mendelian randomization that can identify sets of genetic variants which are suitable in both these respects. Our algorithm is applicable in the context of two-sample summary-data Mendelian randomization and employs a recently proposed theoretical extension of the traditional Bayesian statistics framework, including a loss function to penalize genetic variants that exhibit pleiotropic effects. The algorithm offers robust inference through the use of model averaging, as we illustrate by running it on a range of simulation scenarios and comparing it against established pleiotropy-robust Mendelian randomization methods. In a real data application, we study the effect of systolic and diastolic blood pressure on the risk of suffering from coronary heart disease. Based on a recent large-scale GWAS for blood pressure, we use 395 genetic variants for systolic and 391 variants for diastolic blood pressure. Both traits are shown to have significant risk-increasing effects on coronary heart disease risk.

Abstract 15314: Differential Association of Polymorphic Genetic Variants With Non-Pulmonary Vein Triggers in Patients With Non-Paroxysmal Atrial Fibrillation: Results From a Prospective Study (DECAF)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sanghamitra Mohanty ◽  
Amelia W Hall ◽  
Prasant Mohanty ◽  
Chintan Trivedi ◽  
Luigi Di Biase ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Protective Effect ◽  
Pulmonary Vein ◽  
Genetic Variants ◽  
Multivariate Logistic Regression Analysis ◽  
Cumulative Effect ◽  
Taqman Assay ◽  
Allelic Association ◽  
Kernel Machine ◽  
A Prospective Study

Introduction: Earlier evidences support the origin of ectopic beats from non-pulmonary vein (non-PV) areas that initiate and maintain AF and elimination of these triggers is known to provide better arrhythmia-free survival. Of the different types, non-paroxysmal AF (NPAF) are more prevalently associated with non-PV drivers. Although emerging data on myocytes-fibroblast interactions provide some insight into the pathophysiology of non-PV triggers, the exact mechanism of origin of these ectopic foci is still unknown. Therefore, we examined the association of several AF-specific genetic variants with prevalence of non-PV triggers in NPAF patients undergoing catheter ablation. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS from collected blood samples were performed using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. Multivariate logistic regression analysis (adjusted covariates: age, gender, LA size, hypertension and diabetes) was used for assessing predictive role of individual SNP; and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers. Result: In the non-paroxysmal AF population, significant allelic association was detected between non-PV triggers and rs6599230 (OR 0.57 [95% CI 0.31-0.88], p=0.042) and rs1448817 (OR 1.82 [95%CI 1.12-3.40], p=0.034). Interestingly, rs6599230 suggested a protective effect with 43% risk reduction while rs1448817 was an independent predictor of higher risk of developing non-PV triggers. Conclusion: Our results identified predictive association of two genetic variants, rs6599230 and rs1448817, with non-PV triggers in non-paroxysmal AF patients. Interestingly, the association was distinctive. The SNP, rs6599230 located in close proximity to SCN5A gene, was found to have a protective effect against development of arrhythmogenic triggers in the extra-PV sites whereas rs1448817 on chromosome 4q25 increased the risks of having non-PV triggers.

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

Intrahepatic cholestasis: Analysis of genetic variants in an European cohort

2012 ◽  
Vol 50 (08) ◽  
Author(s):  
M Langhirt ◽  
M Krawczyk ◽  
SN Weber ◽  
F Lammert
Keyword(s):  
Genetic Variants ◽  
Intrahepatic Cholestasis
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