Establishing the relationships between adiposity and reproductive factors: a multivariable Mendelian randomization analysis
dc.contributor.author | Prince, C | |
dc.contributor.author | Howe, LD | |
dc.contributor.author | Sharp, GC | |
dc.contributor.author | Fraser, A | |
dc.contributor.author | Richmond, RC | |
dc.date.accessioned | 2023-10-06T06:38:58Z | |
dc.date.issued | 2023-09-12 | |
dc.date.updated | 2023-10-05T14:48:08Z | |
dc.description.abstract | BACKGROUND: Few studies have investigated associations between adiposity and reproductive factors using causal methods, both of which have a number of consequences on women's health. Here we assess whether adiposity at different points in the lifecourse affects reproductive factors differently and independently, and the plausibility of the impact of reproductive factors on adiposity. METHODS: We used genetic data from UK Biobank (273,238 women) and other consortia (EGG, GIANT, ReproGen and SSGAC) for eight reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners, and two adiposity traits: childhood and adulthood body size. We applied multivariable Mendelian randomization to account for genetic correlation and to estimate the causal effects of childhood and adulthood adiposity, independently of each other, on reproductive factors. Additionally, we estimated the effects of reproductive factors, independently of other relevant reproductive factors, on adulthood adiposity. RESULTS: We found a higher childhood body size leads to an earlier age at menarche, and an earlier age at menarche leads to a higher adulthood body size. Furthermore, we find contrasting and independent effects of childhood and adulthood body size on age at first birth (beta 0.22 SD (95% confidence interval: 0.14, 0.31) vs - 2.49 (- 2.93, - 2.06) per 1 SD increase), age at last birth (0.13 (0.06,0.21) vs - 1.86 (- 2.23, - 1.48) per 1 SD increase), age at menopause (0.17 (0.09, 0.25) vs - 0.99 (- 1.39, - 0.59) per 1 SD increase), and likelihood of having children (Odds ratio 0.97 (0.95, 1.00) vs 1.20 (1.06, 1.37) per 1 SD increase). CONCLUSIONS: Our findings demonstrate the importance of considering a lifecourse approach when investigating the inter-relationships between adiposity measures and reproductive events, as well as the use of 'age specific' genetic instruments when evaluating lifecourse hypotheses in a Mendelian randomization framework. | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Cancer Research UK (CRUK) | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.format.extent | 350- | |
dc.format.medium | Electronic | |
dc.identifier.citation | Vol. 21, article 350 | en_GB |
dc.identifier.doi | https://doi.org/10.1186/s12916-023-03051-x | |
dc.identifier.grantnumber | 108902/B/15/Z | en_GB |
dc.identifier.grantnumber | MR/S009310/1 | en_GB |
dc.identifier.grantnumber | MR/M020894/1 | en_GB |
dc.identifier.grantnumber | C18281/A19169 | en_GB |
dc.identifier.grantnumber | MR/S036520/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/134177 | |
dc.identifier | ORCID: 0000-0003-2906-4035 (Sharp, Gemma C) | |
dc.identifier | ScopusID: 56898577600 (Sharp, Gemma C) | |
dc.language.iso | en | en_GB |
dc.publisher | BMC | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/37697382 | en_GB |
dc.rights | © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | en_GB |
dc.subject | Adiposity | en_GB |
dc.subject | Mendelian randomization | en_GB |
dc.subject | Reproductive factors | en_GB |
dc.subject | UK Biobank | en_GB |
dc.title | Establishing the relationships between adiposity and reproductive factors: a multivariable Mendelian randomization analysis | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-10-06T06:38:58Z | |
exeter.article-number | 350 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available from BMC via the DOI in this record. | en_GB |
dc.description | The availability of all data analysed in this study has been referenced throughout the manuscript and supplementary materials. GWAS summary statistics for age at menarche and menopause from the ReproGen consortium: https://www.reprogen.org/. GWAS summary statistics for age at first birth and number of births from the SSGAC consortium: https://www.thessgac.org/. GWAS summary statistics for childhood BMI from the EGG consortium: http://egg-consortium.org/. GWAS summary statistics for adulthood BMI from the GIANT consortium: https://portals.broadinstitute.org/collaboration/giant/index.php/Main_Page. | en_GB |
dc.identifier.eissn | 1741-7015 | |
dc.identifier.journal | BMC Medicine | en_GB |
dc.relation.ispartof | BMC Med, 21(1) | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-08-25 | |
dc.rights.license | CC BY | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2023-08-25 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-10-06T06:29:40Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-10-06T06:38:59Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-09-12 |
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