Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.

Autor: Thompson WD; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK. wdt204@exeter.ac.uk.; Academic Rheumatology, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom. wdt204@exeter.ac.uk., Reynolds RM; Centre for Cardiovascular Science, The Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK., Beaumont RN; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK., Warrington NM; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.; Frazer Institute, University of Queensland, Brisbane, Australia., Tyrrell J; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK., Wood AR; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK., Evans DM; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.; Frazer Institute, University of Queensland, Brisbane, Australia.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK., McDonald TJ; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.; Academic Department of Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK., Hattersley AH; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK., Freathy RM; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Lawlor DA; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health, Bristol Medical School, University of Bristol, Bristol, UK.; Bristol NIHR Biomedical Research Centre, Bristol, UK., Borges MC; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health, Bristol Medical School, University of Bristol, Bristol, UK.
Jazyk: angličtina
Zdroj: BMC pregnancy and childbirth [BMC Pregnancy Childbirth] 2024 Jan 15; Vol. 24 (1), pp. 65. Date of Electronic Publication: 2024 Jan 15.
DOI: 10.1186/s12884-024-06250-3
Abstrakt: Background: Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding.
Methods: We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant's effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects.
Results: The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy.
Conclusions: Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.
(© 2024. The Author(s).)
Databáze: MEDLINE
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