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Obesity and risk of female reproductive conditions: A Mendelian randomization study

PLoS Medicine Feb 04, 2022

Despite an observed association of obesity with altered risk of many female reproductive conditions, such as polycystic ovary syndrome (PCOS), abnormal uterine bleeding, endometriosis, infertility, and pregnancy-related disorders, uncertainty remains concerning the roles and mechanisms of obesity in the etiology of reproductive disorders. Hence, researchers sought to determine observational and genetically predicted causal correlations between obesity, metabolic hormones, and female reproductive disorders.

  • Obesity and reproductive disease data on up to 257,193 women of European ancestry in UK Biobank and publicly available genome-wide association studies (GWASs) were retrieved and Logistic regression, generalized additive models, and Mendelian randomization (MR) (2-sample, non-linear, and multivariable) were applied on them.

  • Obesity was seen to be positively linked with a range of female reproductive disorders, including uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and pre-eclampsia, in this one of the largest publicly available datasets on human health.

  • Inherited genetic variation linked with obesity is identified to be linked with female reproductive disorders as well, however, differences in the strength of these associations were noted by type of obesity and reproductive condition.

  • As there is a random assignment of the genetic variants at birth, estimation of the effect of obesity on reproductive conditions may be unbiased by environmental and lifestyle factors or reverse causation using this method.

  • Findings suggest a mediating role of hormones, such as leptin, which is secreted by fat cells, and insulin, in the genetic association of obesity with pre eclampsia.

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