Birthweight, Childhood Body Mass Index, Height and Growth, and Risk of Polycystic Ovary Syndrome

Aarestrup, Julie; Pedersen, Dorthe; Thomas, P. E.; Glintborg, Dorte; Holm, Jens-Christian; Bjerregaard, Lise G.; Baker, Jennifer L.

doi:10.1159/000515294

Cited by 6 publications

(7 citation statements)

References 30 publications

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“…In addition to adult BMI, childhood BMI appears to influence the risk of PCOS later on [ 42 , 43 ]. Findings from earlier observational studies including nearly 3000 participants from the Australian Childhood Determinants of Adult Health study ( N =1516) and the biracial USA Babies substudy of the Bogalusa Heart Study ( N =1247) have suggested an association between greater childhood BMI and PCOS among the white population (RR=4.05, 95% CI=1.10–14.83; RR=2.93, 95% CI=1.65–5.22) [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis

Liu

Zhu

Kraft

et al. 2022

BMC Med

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Background The comorbidity between polycystic ovary syndrome (PCOS) and obesity has long been observed in clinical settings, but their shared genetic basis remains unclear. Methods Leveraging summary statistics of large-scale GWAS(s) conducted in European-ancestry populations on body mass index (adult BMI, Nfemale=434,794; childhood BMI, N=39,620), waist-to-hip ratio (WHR, Nfemale=381,152), WHR adjusted for BMI (WHRadjBMI, Nfemale=379,501), and PCOS (Ncase=10,074, Ncontrol=103,164), we performed a large-scale genome-wide cross-trait analysis to quantify overall and local genetic correlation, to identify shared loci, and to infer causal relationship. Results We found positive genetic correlations between PCOS and adult BMI (rg=0.47, P=2.19×10−16), childhood BMI (rg=0.31, P=6.72×10−5), and WHR (rg=0.32, P=1.34×10−10), all withstanding Bonferroni correction. A suggestive significant genetic correlation was found between PCOS and WHRadjBMI (rg=0.09, P=0.04). Partitioning the whole genome into 1703 nearly independent regions, we observed a significant local genetic correlation for adult BMI and PCOS at chromosome 18: 57630483–59020751. We identified 16 shared loci underlying PCOS and obesity-related traits via cross-trait meta-analysis including 9 loci shared between BMI and PCOS (adult BMI and PCOS: 5 loci; childhood BMI and PCOS: 4 loci), 6 loci shared between WHR and PCOS, and 5 loci shared between WHRadjBMI and PCOS. Mendelian randomization (MR) supported the causal roles of both adult BMI (OR=2.92, 95% CI=2.33–3.67) and childhood BMI (OR=2.76, 95% CI=2.09–3.66) in PCOS, but not WHR (OR=1.19, 95% CI=0.93–1.52) or WHRadjBMI (OR=1.03, 95% CI=0.87–1.22). Genetic predisposition to PCOS did not seem to influence the risk of obesity-related traits. Conclusions Our cross-trait analysis suggests a shared genetic basis underlying obesity and PCOS and provides novel insights into the biological mechanisms underlying these complex traits. Our work informs public health intervention by confirming the important role of weight management in PCOS prevention.

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Section: Discussionmentioning

confidence: 99%

Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis

Liu

Zhu

Kraft

et al. 2022

BMC Med

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“…Of note, a large study of adolescent girls demonstrated that PCOS was preceded by a marked z-score increase between birthweight and BMI at diagnosis ( de Zegher et al , 2017 ). Similarly, in a Danish study (n = 65 665), girls age 7–13 years with overweight were at higher risk (Age 7 years: hazard ratio (HR): 2.83, Age 13 years: HR 2.99) of PCOS than those without overweight, with overweight at both time points further increasing the risk ( Aarestrup et al , 2021 ). Christensen et al (2013) (n = 138 502 adolescents age 15–19) demonstrated that higher BMI category increased the PCOS risk further (OR compared to normal weight, overweight: OR 3.85, obese: OR 10.25, extreme obesity: OR 23.1).…”

Section: Resultsmentioning

confidence: 93%

“…Our review highlighted 16 studies investigating the role of childhood/adolescent body composition in PCOS risk; 9 of these were included for systematic review only and 7 were included for both systematic review and meta-analysis ( Hart et al , 2011 ; Rahmanpour et al , 2012 ; Christensen et al , 2013 ; Roe et al , 2013 ; Gümüş et al , 2015 ; Ayonrinde et al , 2016 ; Çinar et al , 2016 ; Oztas et al , 2016 ; de Zegher et al , 2017 ; Li et al , 2017 ; Ates et al , 2018 ; Bedaiwy et al , 2018 ; Kaewnin et al , 2018 ; Wu et al , 2018 ; Koivuaho et al , 2019 ; Aarestrup et al , 2021 ). Of note, a large study of adolescent girls demonstrated that PCOS was preceded by a marked z-score increase between birthweight and BMI at diagnosis ( de Zegher et al , 2017 ).…”

Section: Resultsmentioning

confidence: 99%

“…Obesity/overweight are associated with PCOS, with observational evidence reporting a 33–88% prevalence of overweight/obesity in women with PCOS ( Balen et al , 1995a ; Gambineri et al , 2002 ; Barber et al , 2006 ; Lim et al , 2012 ; Ollila et al , 2016 ; Aarestrup et al , 2021 ). The huge variation in prevalence likely reflects differences in study settings (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Childhood, adolescent, and adulthood adiposity are associated with risk of PCOS: a Mendelian randomization study with meta-analysis

et al. 2023

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STUDY QUESTION What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Excess body fat, even during childhood/adolescence, and metabolic parameters, suggestive of hyperinsulinaemia/insulin resistance, significantly impact the risk of PCOS in a linear fashion. WHAT IS KNOWN ALREADY Observational and Mendelian randomization (MR) data have demonstrated an association between adulthood overweight/obesity and development of PCOS. However, the contribution of body composition in childhood/adolescence to incident PCOS is unclear, as is the influence of childhood overweight/obesity. STUDY DESIGN, SIZE, DURATION We conducted a systematic review and meta-analysis and integrated our results with a previously published systematic review. Two blinded investigators screened abstracts published between November 2010 and May 2021. Furthermore, we incorporated summary statistics from genome-wide association study (GWAS) data in subjects of European ancestry. Adult overweight was defined as BMI ≥ 25 kg/m2 and obesity as BMI ≥ 30 kg/m2; in Asian subjects, overweight was defined as BMI ≥ 23 kg/m2 and obesity as BMI ≥ 25 kg/m2. PARTICIPANTS/MATERIALS, SETTING, METHODS We utilized meta-analysis and MR together to allow synthesis of genetic and observational data. For the systematic review, the search revealed 71 studies, of which 63 were included in meta-analysis by calculating odds ratios (ORs) using the random-effects model. Furthermore, we conducted a two-sample MR study of GWAS data to determine the impact of childhood and adult body size (defined categorically by BMI and childhood body size proportions), abnormal body composition and metabolic parameters (higher fasting serum insulin or lower sex hormone-binding globulin (SHBG) concentration) on the odds of incident PCOS via the inverse-variance weighted method. MAIN RESULTS AND THE ROLE OF CHANCE Significant associations were shown between body composition and PCOS incidence. From the systematic review/meta-analysis, women with overweight (OR 3.80, 2.87–5.03), obesity (OR 4.99, 3.74–6.67), and central obesity (OR 2.93, 2.08–4.12) had increased odds of PCOS. For adolescents with overweight and/or obesity, the PCOS odds were greater than for adults. From MR, for every standard deviation increase in BMI (4.8 kg/m2), the odds of PCOS increased by 2.76 (2.27–3.35). Childhood body size had an independent effect on PCOS odds after adjusting for adult body size (OR: 2.56, 1.57–4.20). Genetically determined body fat percentage (OR 3.05, 2.24–4.15), whole body fat mass (OR 2.53, 2.04–3.14), fasting serum insulin (OR 6.98, 2.02–24.13), and SHBG concentration (OR 0.74, 0.64–0.87) were all significantly associated with PCOS in a linear relation. LIMITATIONS, REASONS FOR CAUTION The meta-analysis included studies which were cross-sectional and retrospective, limiting our ability to determine causality. MR was limited by interrogating subjects only of European ancestry and including cases classified by either self-diagnosis or diagnostic criteria. WIDER IMPLICATIONS OF THE FINDINGS Our study demonstrates for the first time a critical role of the impact of excess childhood/adolescent adiposity on the pathophysiology of adult PCOS. Our results, driven by genetically determined childhood/adolescent body composition, higher BMI, hyperinsulinaemia, and lower SHBG, clearly favour obesity driving the metabolic, but not reproductive, PCOS phenotype. Overall, effective weight maintenance, even from the early years, is likely to reduce the risk of this reproductive endocrine disorder. STUDY FUNDING/COMPETING INTEREST(S) S.S.Z. was funded by a National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship. U.A. is chair of the NIHR Steering Committee Trial—CASSANDRA-DN. No other authors declare any sources of funding or relevant conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relations that could be construed as a potential conflict of interest. TRIAL REGISTRATION NUMBER N/A.

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“… 1 , 5 , 6 The exact etiology of PCOS is not fully known, however, there are several known common triggers, including genetic, hormonal, and environmental factors. 3 Females with low birthweight history, 7 , 8 with low levels of vitamin D, 3 with parental PCOS history, 9 , 10 as well as with childhood overweight or adult obesity, 10 , 11 were reported to be at increased risk for subsequent PCOS.…”

Section: Introductionmentioning

confidence: 99%

Association Between Self-Reported Polycystic Ovary Syndrome with Chronic Diseases Among Emiratis: A Cross-Sectional Analysis from the UAE Healthy Future Study

Juber¹,

Abdulle²,

AlJunaibi³

et al. 2023

IJWH

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Purpose This study aimed to assess the prevalence of self-reported polycystic ovary syndrome (PCOS) among Emiratis and examine bi-directional associations of PCOS with self-reported chronic diseases, namely: diabetes, asthma, high cholesterol, and high blood pressure. Patients and Methods A cross-sectional analysis was performed using the UAE Healthy Future Study (UAEHFS) data collected from February 2016 to April 2022 involving 1040 Emirati women aged 25–67 years from recruitment centers in the United Arab Emirates (UAE). The bi-directional associations between self-reported PCOS and self-reported chronic diseases were evaluated by establishing temporality based on reported age-at-diagnoses. Firstly, the associations between PCOS (diagnosed at ≥25 years) and chronic diseases (diagnosed at <25 years) were examined, followed by PCOS (diagnosed at <25 years) and chronic diseases (diagnosed at ≥25 years). Finally, a Poisson regression under unadjusted and age-and-body mass index (BMI) adjusted models was performed to obtain the risk ratio (RR) and its 95% confidence interval (CI). Results The prevalence of PCOS in this study was 25.9%. Those with asthma and high cholesterol diagnosed at <25 years had increased risks of PCOS diagnosed at ≥25 years (RR = 1.79, 95% CI: 1.17–2.76 for asthma; and RR = 1.61, 95% CI: 1.01–2.59 for high cholesterol), compared to those respective healthier counterparts, after adjusting for age and BMI. No significant association was observed between PCOS diagnosed at <25 years and respective chronic diseases diagnosed at ≥25 years. Conclusion PCOS prevalence among Emirati women was high. Asthma and high cholesterol in earlier life were associated with PCOS in later life. Understanding how chronic disease conditions and PCOS are associated in bi-directional ways may improve the surveillance of chronic disease conditions among women with PCOS and may also contribute to more targeted PCOS prevention strategies.

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Birthweight, Childhood Body Mass Index, Height and Growth, and Risk of Polycystic Ovary Syndrome

Cited by 6 publications

References 30 publications

Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis

Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis

Childhood, adolescent, and adulthood adiposity are associated with risk of PCOS: a Mendelian randomization study with meta-analysis

Association Between Self-Reported Polycystic Ovary Syndrome with Chronic Diseases Among Emiratis: A Cross-Sectional Analysis from the UAE Healthy Future Study

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