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Causality of anthropometric markers associated with polycystic ovarian syndrome : Findings of a Mendelian randomization study

De Silva, Kushan ; Demmer, Ryan T. ; Jönsson, Daniel ; Mousa, Aya ; Teede, Helena ; Forbes, Andrew and Enticott, Joanne (2022) In PLoS ONE 17(6 June).
Abstract

Introduction Using body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed. Objectives To investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers. Methods Summary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables–weight and height), from the IEU Open GWAS... (More)

Introduction Using body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed. Objectives To investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers. Methods Summary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables–weight and height), from the IEU Open GWAS Project. As the outcome, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling. Results Instrumental variables demonstrated no weak instrument bias (F > 10). Four anthropometric exposures, namely, weight (2.69–77.05), BMI (OR: 2.90–4.06), WC (OR: 6.22–20.27), and HC (OR: 6.22–20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS. Conclusions Both and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care.

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Contribution to journal
publication status
published
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in
PLoS ONE
volume
17
issue
6 June
article number
e0269191
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:35679284
  • scopus:85131772059
ISSN
1932-6203
DOI
10.1371/journal.pone.0269191
language
English
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no
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bbc5235a-239e-454f-8218-1e169c8da549
date added to LUP
2022-09-23 09:42:22
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2024-04-15 18:56:10
@article{bbc5235a-239e-454f-8218-1e169c8da549,
  abstract     = {{<p>Introduction Using body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed. Objectives To investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers. Methods Summary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables–weight and height), from the IEU Open GWAS Project. As the outcome, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling. Results Instrumental variables demonstrated no weak instrument bias (F &gt; 10). Four anthropometric exposures, namely, weight (2.69–77.05), BMI (OR: 2.90–4.06), WC (OR: 6.22–20.27), and HC (OR: 6.22–20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS. Conclusions Both and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care.</p>}},
  author       = {{De Silva, Kushan and Demmer, Ryan T. and Jönsson, Daniel and Mousa, Aya and Teede, Helena and Forbes, Andrew and Enticott, Joanne}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{6 June}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Causality of anthropometric markers associated with polycystic ovarian syndrome : Findings of a Mendelian randomization study}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0269191}},
  doi          = {{10.1371/journal.pone.0269191}},
  volume       = {{17}},
  year         = {{2022}},
}