Probing the origins of indirect genetic effects

It's not just what your parents did but what your grand, great-grand, great-great grandparents etc. did.

A new paper in Nature Human Behavior by some of the well-known experts in the Behavioral Genetics field adds some new insights into the origins of indirect genetic effects of educational attainment.

The paper that first popularized the concept of “genetic nurture” among human geneticists (the concept itself is old and well-known to animal geneticists) is, as some of you might remember well, the one from deCODE genetics titled “The nature of nurture: Effects of parental genotypes” published in Science in the year 2018. In the paper, the authors empirically demonstrated genetic nurture for the first time in humans, which was until then known only in the animal genetics literature. Analyzing a multi-generational Icelandic cohort, the authors showed that a polygenic score constructed using the genetic variants observed in the parents but absent in the offspring (non-transmitted polygenic score) significantly predicted the educational attainment of the offspring, explaining up to 30% of the association of transmitted polygenic score. This genetic association between the non-transmitted alleles in the parents and phenotype in the offspring is mediated not by the genetics that the parents pass to their offspring (described as “direct genetic effects”) but through the environment they create for their offspring (described as “indirect genetic effects”).

While everyone in the field agreed on the existence of indirect genetic effects, many debated the origins of such indirect effects. While many argued that they are nurture (that is, things the parents do to help their children study well like buying books, teaching, enrolling in tuition, taking care of the offspring’s health etc.), some argued they are not purely parental nurture but include factors that extend beyond the borders of a nuclear family such as the social status, wealth etc, and some others argued they could be simply confounders of genetic studies such as population stratification. The new findings bring some clarity to this debate.

The authors made excellent use of a multigenerational extended family sample from the Norwegian Mother, Father, and Child Cohort Study (MoBa), performing a polygenic score analysis of school performance using a brilliant study design. The authors constructed polygenic scores using offspring genetics, parents’ genetics and parents’ siblings’ genetics and tested their associations with offspring school performance in a single regression framework.

As expected the parental polygenic score predicted offspring school performance demonstrating the indirect genetic effects. But when the authors accounted for the parents’ siblings’ polygenic score, the parental polygenic score was no longer significantly associated with the offspring's school performance suggesting that the indirect effects are not purely genetic nurture that is confined within a nuclear family but include other environmental factors that are shared with the extended family. The authors speculate that such factors might be the so-called “dynastic effects” such as social status, wealth etc. that are passed through multiple generations and so, shared with extended family members.

It’s a simple and neat study offering important insights into our understanding of the indirect genetic effects. The title of the paper nicely summarizes the paper’s finding: “More than nature and nurture, indirect genetic effects on children’s academic achievement are consequences of dynastic social processes”.