A robust imputation method for missing responses and covariates in sample selection models

Sample selection arises when the outcome of interest is partially observed in a study. Although sophisticated statistical methods in the parametric and non-parametric framework have been proposed to solve this problem, it is yet unclear how to deal with selectively missing covariate data using simple multiple imputation techniques, especially in the absence of exclusion restrictions and deviation from normality. Motivated by the 2003-2004 NHANES data, where previous authors have studied the effect of socio-economic status on blood pressure with missing data on income variable, we proposed the use of a robust imputation technique based on the selection-t sample selection model. The imputation method, which is developed within the frequentist framework, is compared with competing alternatives in a simulation study. The results indicate that the robust alternative is not susceptible to the absence of exclusion restrictions - a property inherited from the parent selection-t model - and performs better than models based on the normal assumption even when the data is generated from the normal distribution. Applications to missing outcome and covariate data further corroborate the robustness properties of the proposed method. We implemented the proposed approach within the MICE environment in R Statistical Software

Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene–gene–environment interaction

Epistatic gene–gene interactions could contribute to the heritability of complex multigenic disorders, but few examples have been reported. Here, we focus on the role of aberrant dopaminergic signaling, involving the dopamine transporter DAT, a cocaine target, and the dopamine D2 receptor, which physically interacts with DAT. Splicing polymorphism rs2283265 of DRD2, encoding D2 receptors, were shown to confer risk of cocaine overdose/death (odds ratio ∼3) in subjects and controls from the Miami Dade County Brain Bank.(1) Risk of cocaine-related death attributable to the minor allele of rs2283265 was significantly enhanced to OR=7.5 (P=0.0008) in homozygous carriers of the main 6-repeat allele of DAT rs3836790, a regulatory VNTR in intron8 lacking significant effect itself. In contrast, carriers of the minor 5-repeat DAT allele showed no significant risk (OR=1.1, P=0.84). DAT rs3836790 and DRD2 rs2283265 also interacted by modulating DAT protein activity in the ventral putamen of cocaine abusers. In high-linkage disequilibrium with the VNTR, DAT rs6347 in exon9 yielded similar results. Assessing the impact of DAT alone, a rare DAT haplotype formed by the minor alleles of rs3836790 and rs27072, a regulatory DAT variant in the 3′-UTR, occurred in nearly one-third of the cocaine abusers but was absent in African American controls, apparently conferring strong risk. These results demonstrate gene–gene–drug interaction affecting risk of fatal cocaine intoxication