Implicating causal brain imaging endophenotypes in Alzheimer's disease using multivariable IWAS and GWAS summary data.

ABSTRACT: Recent evidence suggests the existence of many undiscovered heritable brain phenotypes involved in Alzheimer's Disease (AD) pathogenesis. This finding necessitates methods for the discovery of causal brain changes in AD that integrate Magnetic Resonance Imaging measures and genotypic data. However, existing approaches for causal inference in this setting, such as the univariate Imaging Wide Association Study (UV-IWAS), suffer from inconsistent effect estimation and inflated Type I errors in the presence of genetic pleiotropy, the phenomenon in which a variant affects multiple causal intermediate risk phenotypes. In this study, we implement a multivariate extension to the IWAS model, namely MV-IWAS, to consistently estimate and test for the causal effects of multiple brain imaging endopheno

SUBMITTER: Knutson KA 

PROVIDER: S-EPMC7778364 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature