Age at menopause and lung function: a Mendelian randomisation study

Plaat, Diana A van der; Pereira, Miguel; Pesce, Giancarlo; Potts, James; Amaral, André F.S.; Dharmage, Shyamali C.; Garcia‐Aymerich, Judith; Thompson, John R.; Real, Francisco Gómez; Jarvis, Déborah; Minelli, Cosetta; Leynaert, Bénédicte

doi:10.1183/13993003.02421-2018

Cited by 26 publications

(22 citation statements)

References 44 publications

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“…Fourth, the analysis was repeated by splitting the SNPs into two groups: one based only on SNPs related to DDR genes ( n = 37) and the other based on genes other than DDR [ 11 ]. Fifth, to address potential pleiotropy, the SNPs previously reported as associated with BMI and menarche [ 28 ] were excluded. Finally, an analysis not adjusting for correlation and including the weak SNPs was undertaken.…”

Section: Methodsmentioning

confidence: 99%

Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study

Roa‐Díaz

Asllanaj

Amin

et al. 2021

JCM

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Observational studies suggest that early onset of menopause is associated with increased risk of hypertension. Whether this association is causal or due to residual confounding and/or reverse causation remains undetermined. We aimed to evaluate the observational and causal association between age at natural menopause (ANM) and blood pressure traits in Caucasian women. A cross-sectional and one-sample Mendelian randomization (MR) study was conducted in 4451 postmenopausal women from the CoLaus and Rotterdam studies. Regression models were built with observational data to study the associations of ANM with systolic and diastolic blood pressure (SBP/DBP) and hypertension. One-sample MR analysis was performed by calculating a genetic risk score of 54 ANM-related variants, previously identified in a genome-wide association study (GWAS) on ANM. In the two-sample MR analysis we used the estimates from the ANM-GWAS and association estimates from 168,575 women of the UK Biobank to evaluate ANM-related variants and their causal association with SBP and DBP. Pooled analysis from both cohorts showed that a one-year delay in menopause onset was associated with 2% (95% CI 0; 4) increased odds of having hypertension, and that early menopause was associated with lower DBP (β = −1.31, 95% CI −2.43; −0.18). While one-sample MR did not show a causal association between ANM and blood pressure traits, the two-sample MR showed a positive causal association of ANM with SBP; the last was driven by genes related to DNA damage repair. The present study does not support the hypothesis that early onset of menopause is associated with higher blood pressure. Our results suggest different ANM-related genetic pathways could differently impact blood pressure.

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Section: Methodsmentioning

confidence: 99%

Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study

Roa‐Díaz

Asllanaj

Amin

et al. 2021

JCM

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“…Observational studies suggest that lower forced vital capacity (FVC) and a higher risk of spirometric restriction is associated with an earlier age at menopause. A Mendelian randomization study suggests that ANM lowering SNPs were associated with a 15% lower risk of spirometric restriction (van der Plaat et al, 2019). Entering menopause at an earlier age seems to have a positive effect on airflow obstruction (van der Plaat et al, 2019).…”

Section: Other Traitsmentioning

confidence: 99%

“…A Mendelian randomization study suggests that ANM lowering SNPs were associated with a 15% lower risk of spirometric restriction (van der Plaat et al, 2019). Entering menopause at an earlier age seems to have a positive effect on airflow obstruction (van der Plaat et al, 2019). Further studies are needed to investigate the underlying mechanisms and the role of female sex hormones in lung function.…”

Section: Other Traitsmentioning

confidence: 99%

Shared Genetics Between Age at Menopause, Early Menopause, POI and Other Traits

Louwers

Visser

2021

Front. Genet.

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Reproductive ageing leading to menopause is characterized by depletion of follicles and its regulating mechanisms are only partly understood. Early age at menopause and premature ovarian insufficiency (POI) are associated with several other traits such as cardiovascular disease, dyslipidemia, osteoporosis and diabetes. In large cohorts of Northern European women hundreds of Single Nucleotide Polymorphisms (SNPs) have been identified to be associated with age at menopause. These SNPs are located in genes enriched for immune and mitochondrial function as well as DNA repair and maintenance processes. Genetic predisposition to earlier menopause might also increase the risk of other associated traits. Increased risk for cardiovascular disease in women has been associated with age at menopause lowering SNPs. Pleiotropy between early age at menopause and increased mortality from coronary artery disease has been observed, implicating that genetic variants affecting age at menopause also affect the risk for coronary deaths. This review will discuss the shared genetics of age at menopause with other traits. Mendelian Randomization studies implicate causal genetic association between age at menopause and age at menarche, breast cancer, ovarian cancer, BMD and type 2 diabetes. Although the shared biological pathways remain to be determined, mechanisms that regulate duration of estrogen exposure remain an important focus.

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“…However, early menopause is also associated with a 13% higher risk of lung restriction. Future research is needed to explain this result [119].…”

Section: Menstrual Cycle and Menopausementioning

confidence: 91%

“…Although the literature is still limited, there is a general consensus, based on different population-based longitudinal surveys carried out on wide samples [119][120][121], that menopause is associated with lower lung function and more respiratory symptoms. Menopause is associated with accelerated lung function decline, beyond the expected age change.…”

Section: Menstrual Cycle and Menopausementioning

confidence: 99%

Sex and gender in respiratory physiology

LoMauro

Aliverti

2021

Eur Respir Rev

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Sex is a biological concept determined at conception. Gender is a social concept. Medicine recognises sex as a biological variable and recommends including sex as a factor in clinical practice norms and as a topic of bench and clinical research. Sex plays a role in respiratory physiology according to two pathways: hormones and anatomy, with females characterised by smaller dimensions at every level of the respiratory system. Sex hormones also play specific roles in lung inflammatory processes, breathing control and in response to diseases. The literature is extremely controversial because many factors need to be considered to avoid erroneous comparisons. The main difficulty lies in creating homogeneous groups of subjects according to age, body weight, lung/airway size, fluctuations in circulating hormone levels, and exercise protocol. Because almost all of the knowledge available in physiology is based on research in males, medicine for women is therefore less evidence-based than that being applied to men. Finally, the number of transsexual people is increasing and they represent new challenges for clinicians, due to the anatomical and physiological changes that they undergo.

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Age at menopause and lung function: a Mendelian randomisation study

Cited by 26 publications

References 44 publications

Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study

Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study

Shared Genetics Between Age at Menopause, Early Menopause, POI and Other Traits

Sex and gender in respiratory physiology

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