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Polygenic differential susceptibility to prenatal adversity

  • Jay Belsky (a1), Irina Pokhvisneva (a2), Anu Sathyan Sathyapalan Rema (a3), Birit F.P. Broekman (a3), Michael Pluess (a4), Kieran J. O'Donnell (a2) (a5) (a6), Michael J. Meaney (a2) (a3) (a5) (a6) and Patrícia P. Silveira (a2) (a5) (a6)...


A recent article in this journal reported a number of gene × environment interactions involving a serotonin transporter–gene network polygenic score and a composite index of prenatal adversity predicting several problem behavior outcomes at 48 months (e.g., anxious/depressed, pervasive developmental problems) and at 60 months (e.g., withdrawal, internalizing problems), yet did not illuminate the nature or form these genetic × environment interactions took. Here we report results of six additional analyses to evaluate whether these interactions reflected diathesis–stress or differential–susceptibility related processes. Analyses of the regions of significance and proportion of interaction index are consistent with the diathesis–stress model, seemingly because of the truncated nature of the adversity score (which did not extend to supportive/positive prenatal experiences/exposures); in contrast, the proportion (of cases) affected index favors the differential–susceptibility model. These results suggest the need for future studies to extend measurement of the prenatal environment to highly supportive experiences and exposures.


Corresponding author

Address correspondence and reprint requests to: Patricia Pelufo Silveira, MD, PhD Department of Psychiatry, McGill University Douglas Mental Health University Institute, 6875 Boulevard LaSalle, Montreal, Quebec, H4H 1R3, Canada; E-mail:


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The authors have no conflicts of interest to declare.



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