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Identifying Genetic Variants for Addiction via Propensity Score Adjusted Generalized Kendall's Tau.

ABSTRACT: Identifying replicable genetic variants for addiction has been extremely challenging. Besides the common difficulties with genome-wide association studies (GWAS), environmental factors are known to be critical to addiction, and comorbidity is widely observed. Despite the importance of environmental factors and comorbidity for addiction study, few GWAS analyses adequately considered them due to the limitations of the existing statistical methods. Although parametric methods have been developed to adjust for covariates in association analysis, difficulties arise when the traits are multivariate because there is no ready-to-use model for them. Recent nonparametric development includes U-statistics to measure the phenotype-genotype association weighted by a similarity score of covariates. However, it is not clear how to optimize the similarity score. Therefore, we propose a semiparametric method to measure the association adjusted by covariates. In our approach, the nonparametric U-statistic is adjusted by parametric estimates of propensity scores using the idea of inverse probability weighting. The new measurement is shown to be asymptotically unbiased under our null hypothesis while the previous non-weighted and weighted ones are not. Simulation results show that our test improves power as opposed to the non-weighted and two other weighted U-statistic methods, and it is particularly powerful for detecting gene-environment interactions. Finally, we apply our proposed test to the Study of Addiction: Genetics and Environment (SAGE) to identify genetic variants for addiction. Novel genetic variants are found from our analysis, which warrant further investigation in the future.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC4219655 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Identifying Genetic Variants for Addiction via Propensity Score Adjusted Generalized Kendall's Tau.

Jiang Yuan Y Li Ni N Zhang Heping H

Journal of the American Statistical Association 20140101 507

Identifying replicable genetic variants for addiction has been extremely challenging. Besides the common difficulties with genome-wide association studies (GWAS), environmental factors are known to be critical to addiction, and comorbidity is widely observed. Despite the importance of environmental factors and comorbidity for addiction study, few GWAS analyses adequately considered them due to the limitations of the existing statistical methods. Although parametric methods have been developed to ...[more]

PMID: 25382885

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Project description:AimsThe mortality in cardiogenic shock (CS) is high. The role of specific mechanical circulatory support (MCS) systems is unclear. We aimed to compare patients receiving Impella versus ECLS (extracorporal life support) with regard to baseline characteristics, feasibility, and outcomes in CS.Methods and resultsThis is a retrospective cohort study including CS patients over 18 years with a complete follow-up of the primary endpoint and available baseline lactate level, receiving haemodynamic support either by Impella 2.5 or ECLS from two European registries. The decision for device implementation was made at the discretion of the treating physician. The primary endpoint of this study was all-cause mortality at 30 days. A propensity score for the use of Impella was calculated, and multivariable logistic regression was used to obtain adjusted odds ratios (aOR). In total, 149 patients were included, receiving either Impella (n = 73) or ECLS (n = 76) for CS. The feasibility of device implantation was high (87%) and similar (aOR: 3.14; 95% CI: 0.18-56.50; P = 0.41) with both systems. The rates of vascular injuries (aOR: 0.95; 95% CI: 0.10-3.50; P = 0.56) and bleedings requiring transfusions (aOR: 0.44; 95% CI: 0.09-2.10; P = 0.29) were similar in ECLS patients and Impella patients. The use of Impella or ECLS was not associated with increased odds of mortality (aOR: 4.19; 95% CI: 0.53-33.25; P = 0.17), after correction for propensity score and baseline lactate level. Baseline lactate level was independently associated with increased odds of 30 day mortality (per mmol/L increase; OR: 1.29; 95% CI: 1.14-1.45; P < 0.001).ConclusionsIn CS patients, the adjusted mortality rates of both ECLS and Impella were high and similar. The baseline lactate level was a potent predictor of mortality and could play a role in patient selection for therapy in future studies. In patients with profound CS, the type of device is likely to be less important compared with other parameters including non-cardiac and neurological factors.

Dataset Information

Identifying Genetic Variants for Addiction via Propensity Score Adjusted Generalized Kendall's Tau.

Publications

Identifying Genetic Variants for Addiction via Propensity Score Adjusted Generalized Kendall's Tau.

Similar Datasets

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