Dataset Information

Combining Structural-Equation Modeling with Genomic-Relatedness-Matrix Restricted Maximum Likelihood in OpenMx.

ABSTRACT: There is a long history of fitting biometrical structural-equation models (SEMs) in the pregenomic behavioral-genetics literature of twin, family, and adoption studies. Recently, a method has emerged for estimating biometrical variance-covariance components based not upon the expected degree of genetic resemblance among relatives, but upon the observed degree of genetic resemblance among unrelated individuals for whom genome-wide genotypes are available-genomic-relatedness-matrix restricted maximum-likelihood (GREML). However, most existing GREML software is concerned with quickly and efficiently estimating heritability coefficients, genetic correlations, and so on, rather than with allowing the user to fit SEMs to multitrait samples of genotyped participants. We therefore introduce a feature in the OpenMx package, "mxGREML", designed to fit the biometrical SEMs from the pregenomic era in present-day genomic study designs. We explain the additional functionality this new feature has brought to OpenMx, and how the new functionality works. We provide an illustrative example of its use. We discuss the feature's current limitations, and our plans for its further development.

SUBMITTER: Kirkpatrick RM

PROVIDER: S-EPMC8096671 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Combining Structural-Equation Modeling with Genomic-Relatedness-Matrix Restricted Maximum Likelihood in OpenMx.

Kirkpatrick Robert M RM Pritikin Joshua N JN Hunter Michael D MD Neale Michael C MC

Behavior genetics 20210113 3

There is a long history of fitting biometrical structural-equation models (SEMs) in the pregenomic behavioral-genetics literature of twin, family, and adoption studies. Recently, a method has emerged for estimating biometrical variance-covariance components based not upon the expected degree of genetic resemblance among relatives, but upon the observed degree of genetic resemblance among unrelated individuals for whom genome-wide genotypes are available-genomic-relatedness-matrix restricted maxi ...[more]

PMID: 33439421

Similar Datasets

Project description:Mediation analysis is commonly used to identify mechanisms and intermediate factors between causes and outcomes. Studies drawing on polygenic scores (PGSs) can readily employ traditional regression-based procedures to assess whether trait M mediates the relationship between the genetic component of outcome Y and outcome Y itself. However, this approach suffers from attenuation bias, as PGSs capture only a (small) part of the genetic variance of a given trait. To overcome this limitation, we developed MA-GREML: a method for Mediation Analysis using Genome-based Restricted Maximum Likelihood (GREML) estimation. Using MA-GREML to assess mediation between genetic factors and traits comes with two main advantages. First, we circumvent the limited predictive accuracy of PGSs that regression-based mediation approaches suffer from. Second, compared to methods employing summary statistics from genome-wide association studies, the individual-level data approach of GREML allows to directly control for confounders of the association between M and Y. In addition to typical GREML parameters (e.g., the genetic correlation), MA-GREML estimates (i) the effect of M on Y, (ii) the direct effect (i.e., the genetic variance of Y that is not mediated by M), and (iii) the indirect effect (i.e., the genetic variance of Y that is mediated by M). MA-GREML also provides standard errors of these estimates and assesses the significance of the indirect effect. We use analytical derivations and simulations to show the validity of our approach under two main assumptions, viz., that M precedes Y and that environmental confounders of the association between M and Y are controlled for. We conclude that MA-GREML is an appropriate tool to assess the mediating role of trait M in the relationship between the genetic component of Y and outcome Y. Using data from the US Health and Retirement Study, we provide evidence that genetic effects on Body Mass Index (BMI), cognitive functioning and self-reported health in later life run partially through educational attainment. For mental health, we do not find significant evidence for an indirect effect through educational attainment. Further analyses show that the additive genetic factors of these four outcomes do partially (cognition and mental health) and fully (BMI and self-reported health) run through an earlier realization of these traits.

Dataset Information

Combining Structural-Equation Modeling with Genomic-Relatedness-Matrix Restricted Maximum Likelihood in OpenMx.

Publications

Combining Structural-Equation Modeling with Genomic-Relatedness-Matrix Restricted Maximum Likelihood in OpenMx.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets