Introducing M-GCTA a Software Package to Estimate Maternal (or Paternal) Genetic Effects on Offspring Phenotypes.

There is increasing interest within the genetics community in estimating the relative contribution of parental genetic effects on offspring phenotypes. Here we describe the user-friendly M-GCTA software package used to estimate the proportion of phenotypic variance explained by maternal (or alternatively paternal) and offspring genotypes on offspring phenotypes. The tool requires large studies where genome-wide genotype data are available on mother- (or alternatively father-) offspring pairs. The software includes several options for data cleaning and quality control, including the ability to detect and automatically remove cryptically related pairs of individuals. It also allows users to construct genetic relationship matrices indexing genetic similarity across the genome between parents and offspring, enabling the estimation of variance explained by maternal (or alternatively paternal) and offspring genetic effects. We evaluated the performance of the software using a range of data simulations and estimated the computing time and memory requirements. We demonstrate the use of M-GCTA on previously analyzed birth weight data from two large population based birth cohorts, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother and Child Cohort Study (MoBa). We show how genetic variation in birth weight is predominantly explained by fetal genetic rather than maternal genetic sources of variation.

Maternal and paternal effects on offspring internalizing problems: Results from genetic and family-based analyses.

It is unclear to what extent parental influences on the development of internalizing problems in offspring are explained by indirect genetic effects, reflected in the environment provided by the parent, in addition to the genes transmitted from parent to child. In this study, these effects were investigated using two innovative methods in a large birth cohort. Using maternal-effects genome complex trait analysis (M-GCTA), the effects of offspring genotype, maternal or paternal genotypes, and their covariance on offspring internalizing problems were estimated in 3,801 mother-father-child genotyped trios. Next, estimated genetic correlations within pedigree data, including 10,688 children, were used to estimate additive genetic effects, maternal and paternal genetic effects, and a shared family effect using linear mixed effects modeling. There were no significant maternal or paternal genetic effects on offspring anxiety or depressive symptoms at age 8, beyond the effects transmitted via the genetic pathway between parents and children. However, indirect maternal genetic effects explained a small, but nonsignificant, proportion of variance in childhood depressive symptoms in both the M-GCTA (~4%) and pedigree (~8%) analyses. Our results suggest that parental effects on offspring internalizing problems are predominantly due to transmitted genetic variants, rather than the indirect effect of parental genes via the environment.