Genetically adjusted propensity score matching

Abstract

Discordant monozygotic (MZ) twin methodologies are considered one of the foremost statistical approaches for estimating the influence of environmental factors on phenotypic variance. Limitations associated with the discordant MZ twin approach generates an inability to estimate particular relationships and adjust estimates for the confounding influence of gene-nonshared environment interactions. Recent advancements in molecular genetics, however, can provide the opportunity to address these limitations. The current study reviews an alternative technique, genetically adjusted propensity scores (GAPS) matching, that integrates observed genetic and environmental information to adjust for the confounding of these factors in nonkin individuals. Simulations and a real data example were used to compare the GAPS matching approach to the discordant MZ twin method. Although the results of the simulated comparisons demonstrated that the discordant MZ twin approach remains the more robust statistical technique to adjust for shared environmental and genetic factors, GAPS matching - under certain conditions - could represent a viable alternative when MZ twin samples are unavailable. Overall, the findings suggest that GAPS matching can potentially provide an alternative to the discordant MZ twin approach when limited variation exists between identical twin pairs. Moreover, the ability to adjust for gene-nonshared environment interactions represents a potential advancement associated with the GAPS approach. The limitations of the approach, as well as polygenic risk scores, are also discussed.