Table 1 Genetic effects

A variant allele may increase the risk of a disease only when carried by an individual himself/herself. We refer to this as a “child effect” since it is frequently estimated from the offspring in a case-parent triad. However, the individual referred to as a child might be of any age, depending on the phenotype of interest, and the same effect can also be estimated in case-control studies.

A PoO effect occurs if the effect of a variant allele in the child depends on whether it is inherited from the mother or the father. In statistical terms, we define a PoO effect as the interaction effect RRR=RR_M,j/RR_F,j, which is a measure of the risk increase (or decrease) associated with allele A_j, when derived from the mother as opposed to the father. In contrast, regular child-effect analyses assume that the effect of an allele in the child is independent of parental origin. Note that genomic imprinting (an epigenetic phenomenon where one of the inherited parental alleles is expressed whereas the other is silenced) may cause PoO effects [32].

A mother’s genotype may influence fetal development directly, for example through maternal metabolic factors operating in utero [33], and may affect health throughout life [34]. A maternal effect occurs when a variant allele carried by the mother increases the risk of disease in her child, regardless of whether or not the allele has been transferred to the child [35]. This is distinct from child and PoO effects, in which we measure the effect of alleles in the child himself/herself. Because these underlying genetic mechanisms lead to entirely different biological interpretations, distinguishing between the genetic effects is particularly important in advancing the understanding of the etiology underlying a complex disease [11, 36, 37].