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Disentangling prenatal and inherited influences in humans with an experimental design

Rice, Frances ORCID:, Harold, Gordon Thomas, Boivin, Jacky ORCID:, Hay, Dale F. ORCID:, van den Bree, Marianne Bernadette ORCID: and Thapar, Anita ORCID: 2009. Disentangling prenatal and inherited influences in humans with an experimental design. Proceedings of the National Academy of Sciences of the United States of America 106 (7) , pp. 2464-2467. 10.1073/pnas.0808798106

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Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RG Gynecology and obstetrics
Uncontrolled Keywords: child; psychopathology; genetic; antisocial behavior; birth weight
Publisher: American Academy of Sciences
ISSN: 0027-8424
Last Modified: 06 May 2023 01:39

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