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A unified framework for the estimation of polygenic direct effect, indirect effect, and GxE interactions in case-parent trio studies

Usage

PGS.TRI(
  pgs_offspring,
  pgs_mother,
  pgs_father,
  GxE_int = FALSE,
  parental_indirect = FALSE,
  formula = ~envir1 + envir2 + factor(s1),
  E,
  side = 2,
  smalltriosize = FALSE
)

Arguments

pgs_offspring

The PGS values of the affected probands (children). A vector of length N, no missing values are allowed

pgs_mother

The PGS values of mothers that corresponds to the children. A vector of same length N, no missing values are allowed

pgs_father

The PGS values of fathers that corresponds to the children. A vector of same length N, no missing values are allowed

GxE_int

Whether there are interaction effect between pgs and environmental variables that are of interest in the model. If FALSE, then "formula" and "E" are ignored.

parental_indirect

Whether to estimate potential parental indirent effect, returns an estimated difference of mother and father parental effect (delta_MF = beta_M - beta_F).

formula

The environmental variables of interest for the PGSxE interaction effect

E

The environmental variables of interest for interaction effect. A vector of length N for one environmental variable or a data frame/data matrix of NxP for P environmental variables are allowed.

side

Sided of the Wald test or t test, default is 2-sided.

smalltriosize

Whether number of trios is small (<100), if TRUE, a t test will be used rather than a wald test.

Value

A list of results of PGS.TRI

Coefficients_direct

Results of direct PGS effect, if GxE_int is TRUE, then the result will also include PGSxE interaction effects

Coefficients_indirect

Results of indirect parental PGS effect difference: PGS_mother - PGS_father

var_fam

Within-family variances for each family

var_fam_sum

Sum of within-family variances

log_LC

Log likelihood of the offspring's transmission component

log_LP_profile

The log profile likelihood of parents' component, note that we can report this likelihood when only considering direct effects in the model

log_likelihood

Results of the final log-likelihood. This is calculated as the sum of the offspring's and parents' components

vcov

Variance-covariance matrix of coefficients for direct genetic effects and gene–environment interaction terms (PGS×E)