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Editorial |

Quantifying the Effects of Rare Variants in Pedigrees How Far Does the Apple Fall From the Tree?

Eric M. Morrow, PhD, MD1,2,3,4
[+] Author Affiliations
1Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island
2Institute for Brain Science, Laboratory for Molecular Medicine, Brown University, Providence, Rhode Island
3Developmental Disorders Genetics Research Program, Emma Pendleton Bradley Hospital, East Providence, Rhode Island
4Department of Psychiatry and Human Behavior, Brown University Medical School, Providence, Rhode Island
JAMA Psychiatry. 2015;72(2):106-107. doi:10.1001/jamapsychiatry.2014.2442.
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“The apple doesn’t fall far from the tree.” This maxim presents the intuitive notion that, for reasons related to inherited genes, environment, or most likely both, a child’s phenotype correlates with the parents’ phenotype. In this issue of JAMA Psychiatry, Moreno-De-Luca et al1 quantify the effect size of de novo 16p11.2 deletions on continuous phenotypes by comparing the child’s phenotype with the parents’. In essence, they measure the distance that a spontaneous genetic mutation leads the apple to roll away from the tree. Their analysis is conducted on family data from the thoughtfully designed Simons Variation in Individuals Project (Simons VIP), which includes a large number of families with the same recurrent deletion between breakpoints 4 and 5 at 16p11.2.2 The results emphasize several current concepts emerging in the area of rare genetic variation and psychiatric diagnosis and also present compelling possibilities for experiments in the future.

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