Abstract
In the classical twin study, phenotypic variation is often partitioned into additive genetic (A), common (C) and specific environment (E) components. From genetical theory, the outcome of genotype by environment interaction is expected to inflate A when the interacting factor is shared (i.e., C) between the members of a twin pair. We show that estimates of both A and C can be inflated. When the shared interacting factor changes the size of the difference between homozygotes’ means, the expected sibling or DZ twin correlation is .5 if and only if the minor allele frequency (MAF) is .5; otherwise the expected DZ correlation is greater than this value, consistent (and confounded) with some additional effect of C. This result is considered in the light of the distribution of minor allele frequencies for polygenic traits. Also discussed is whether such interactions take place at the locus level or affect an aggregated biological structure or system. Interactions with structures or endophenotypes that result from the aggregated effects of many loci will generally emerge as part of the A estimate.
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Acknowledgments
The authors are grateful for comments from Drs. Lindon Eaves, Mark Reimers and Greg Carey on the results described in this article, and from discussions arising from the simulations presented at the 2013 BGA Annual Meeting in Marseille. This research was supported by NIDA Grants R01DA-018673 and R25DA-26119.
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Brad Verhulst and Michael C. Neale declare that they have no conflicts of interest.
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Verhulst, B., Neale, M.C. Minor Allele Frequency Changes the Nature of Genotype by Environment Interactions. Behav Genet 46, 726–733 (2016). https://doi.org/10.1007/s10519-016-9795-1
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DOI: https://doi.org/10.1007/s10519-016-9795-1