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Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects

Thapar, Anita, Harold, Gordon Thomas, Rice, Frances, Ge, XiaoJia, Boivin, Jacky, Hay, Dale F., van den Bree, Marianne Bernadette and Lewis, Allyson 2007. Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects. BMC Medical Research Methodology 7 (1) , pp. 25-32. 10.1186/1471-2288-7-25

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Abstract

Background There is much evidence to suggest that risk for common clinical disorders begins in foetal life. Exposure to environmental risk factors however is often not random. Many commonly used indices of prenatal adversity (e.g. maternal gestational stress, gestational diabetes, smoking in pregnancy) are influenced by maternal genes and genetically influenced maternal behaviour. As mother provides the baby with both genes and prenatal environment, associations between prenatal risk factors and offspring disease maybe attributable to true prenatal risk effects or to the 'confounding' effects of genetic liability that are shared by mother and offspring. Cross-fostering designs, including those that involve embryo transfer have proved useful in animal studies. However disentangling these effects in humans poses significant problems for traditional genetic epidemiological research designs. Methods We present a novel research strategy aimed at disentangling maternally provided pre-natal environmental and inherited genetic effects. Families of children aged 5 to 9 years born by assisted reproductive technologies, specifically homologous IVF, sperm donation, egg donation, embryo donation and gestational surrogacy were contacted through fertility clinics and mailed a package of questionnaires on health and mental health related risk factors and outcomes. Further data were obtained from antenatal records. Results To date 741 families from 18 fertility clinics have participated. The degree of association between maternally provided prenatal risk factor and child outcome in the group of families where the woman undergoing pregnancy and offspring are genetically related (homologous IVF, sperm donation) is compared to association in the group where offspring are genetically unrelated to the woman who undergoes the pregnancy (egg donation, embryo donation, surrogacy). These comparisons can be then examined to infer the extent to which prenatal effects are genetically and environmentally mediated. Conclusion A study based on children born by IVF treatment and who differ in genetic relatedness to the woman undergoing the pregnancy is feasible. The present report outlines a novel experimental method that permits disaggregation of maternally provided inherited genetic and post-implantation prenatal effects.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Q Science > QH Natural history > QH426 Genetics
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1471-2288/ (accessed 25/02/2014)
Publisher: BioMed Central
ISSN: 1471-2288
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Feb 2019 00:15
URI: http://orca.cf.ac.uk/id/eprint/11486

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