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Article: Menstrual cycle features in mothers and daughters in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Sawyer, Gemma / Howe, Laura D / Fraser, Abigail / Clayton, Gemma / Lawlor, Deborah A / Sharp, Gemma C

Wellcome open research

2023 Volume 8, Page(s) 386

Abstract: Problematic menstrual cycle features, including irregular periods, severe pain, heavy bleeding, absence of periods, frequent or infrequent cycles, and premenstrual symptoms, are experienced by high proportions of females and can have substantial impacts ... ...

Abstract	Problematic menstrual cycle features, including irregular periods, severe pain, heavy bleeding, absence of periods, frequent or infrequent cycles, and premenstrual symptoms, are experienced by high proportions of females and can have substantial impacts on their health and well-being. However, research aimed at identifying causes and risk factors associated with such menstrual cycle features is sparse and limited. This data note describes prospective, longitudinal data collected in a UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), on menstrual cycle features, which can be utilised to address the research gaps in this area. Data were collected across 21 timepoints (between the average age of 28.6 and 57.7 years) in mothers (G0) and 20 timepoints (between the average age of 8 and 24 years) in index daughters (G1) between 1991 and 2020. This data note details all available variables, proposes methods to derive comparable variables across data collection timepoints, and discusses important limitations specific to each menstrual cycle feature. Also, the data note identifies broader issues for researchers to consider when utilising the menstrual cycle feature data, such as hormonal contraception, pregnancy, breastfeeding, and menopause, as well as missing data and misclassification.
Language	English
Publishing date	2023-11-24
Publishing country	England
Document type	Journal Article
ISSN	2398-502X
ISSN	2398-502X
DOI	10.12688/wellcomeopenres.19774.3
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Article ; Online: Menarche, Menstruation, Menopause and Mental Health (4M): a consortium facilitating interdisciplinary research at the intersection of menstrual and mental health.

Sharp, Gemma C / De Giorgio, Luana

Frontiers in global women's health

2023 Volume 4, Page(s) 1258973

Abstract: Menstrual and mental health form a close relationship that is under-appreciated in scientific research, clinical practice and social policy. This association is extremely complex, involving interactions between biology, psychology and social, political ... ...

Abstract	Menstrual and mental health form a close relationship that is under-appreciated in scientific research, clinical practice and social policy. This association is extremely complex, involving interactions between biology, psychology and social, political and structural influences on health and wellbeing. Research in these areas has traditionally been siloed: focusing on menstrual or mental health in isolation, or the interrelation from a limited one-dimensional perspective. We recognised the need for a more holistic and comprehensive approach that considers the complex interweaving nature of menstrual and mental health. In 2021, we established the Menarche, Menstruation, Menopause and Mental Health (4M) consortium as a tool to address this gap and to facilitate interdisciplinary research. This paper provides a comprehensive source of information about 4M for researchers and stakeholders who may be interested in joining or working with the consortium.
Language	English
Publishing date	2023-08-29
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-5059
ISSN (online)	2673-5059
DOI	10.3389/fgwh.2023.1258973
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Article ; Online: COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.

Maybin, Jacqueline A / Watters, Marianne / Rowley, Bethan / Walker, Catherine A / Sharp, Gemma C / Alvergne, Alexandra

Clinical science (London, England : 1979)

2024 Volume 138, Issue 4, Page(s) 153–171

Abstract: The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 ... ...

Abstract	The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood. This review evaluates the published literature on COVID-19 and its impact on menstrual bleeding, discussing the strengths and limitations of these studies. We present evidence consistent with SARS-CoV-2 infection and long COVID having an association with changes in menstrual bleeding parameters and that the impact of COVID vaccination on menstruation appears less significant. An overview of menstrual physiology and known causes of abnormal uterine bleeding (AUB) is provided before discussing potential mechanisms which may underpin the menstrual disturbance reported with COVID-19, highlighting areas for future scientific study. Finally, consideration is given to the effect that menstruation may have on COVID-19, including the impact of the ovarian sex hormones on acute COVID-19 severity and susceptibility and reported variation in long COVID symptoms across the menstrual cycle. Understanding the current evidence and addressing gaps in our knowledge in this area are essential to inform public health policy, direct the treatment of menstrual disturbance and facilitate development of new therapies, which may reduce the severity of COVID-19 and improve quality of life for those experiencing long COVID.
MeSH term(s)	Female ; Humans ; Endometrium ; Post-Acute COVID-19 Syndrome ; Quality of Life ; COVID-19 Vaccines ; COVID-19/complications ; SARS-CoV-2 ; Menstruation/physiology ; Uterine Hemorrhage/etiology ; Menstruation Disturbances/complications
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20220280
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Article ; Online: The impact of paternal alcohol, tobacco, caffeine use and physical activity on offspring mental health: a systematic review and meta-analysis.

Easey, Kayleigh E / Sharp, Gemma C

Reproductive health

2021 Volume 18, Issue 1, Page(s) 214

Abstract: Background: There is some evidence that paternal health behaviours during and around pregnancy could be associated with offspring health outcomes. However, the impact that paternal health behaviours during pregnancy can have on offspring mental health ... ...

Abstract	Background: There is some evidence that paternal health behaviours during and around pregnancy could be associated with offspring health outcomes. However, the impact that paternal health behaviours during pregnancy can have on offspring mental health is understudied and remains unclear. Methods: We conducted a systematic review and meta-analysis of articles in PubMed describing studies of potentially modifiable paternal health behaviours (tobacco smoking, alcohol consumption, caffeine consumption and physical activity) in the prenatal period in relation to offspring mental health. GRADE was used to measure risk of bias. Results: Eight studies were included and categorized by paternal health behaviour and offspring mental health outcome investigated. The narrative synthesis provided evidence of association between paternal health behaviours around pregnancy and offspring mental health problems, with the strongest evidence shown for tobacco use. Grouped by analysis type, two separate meta-analyses showed evidence of paternal smoking during pregnancy being associated with greater odds of ADHD in offspring (OR 1.42, 95% CI 1.02-1.99; HR 1.28, 95% CI 1.19-1.39). Conclusions: The small number of studies that have investigated paternal prenatal effects on offspring mental health, and the limited sample sizes of those studies, makes it challenging to draw firm conclusions. Although existing studies suggest that paternal tobacco smoking and alcohol consumption in the prenatal period are associated with poorer offspring mental health, (particularly hyperactivity/ADHD), further investigation of potential paternal effects is required, using methods that allow stronger inference to determine whether associations are causal.
MeSH term(s)	Alcohol Drinking/adverse effects ; Alcohol Drinking/epidemiology ; Caffeine ; Exercise ; Humans ; Mental Health ; Pregnancy ; Risk Factors ; Nicotiana ; Tobacco Use
Chemical Substances	Caffeine (3G6A5W338E)
Language	English
Publishing date	2021-10-26
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review ; Systematic Review
ZDB-ID	2149029-6
ISSN	1742-4755 ; 1742-4755
ISSN (online)	1742-4755
ISSN	1742-4755
DOI	10.1186/s12978-021-01266-w
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Article ; Online: Establishing the relationships between adiposity and reproductive factors: a multivariable Mendelian randomization analysis.

Prince, Claire / Howe, Laura D / Sharp, Gemma C / Fraser, Abigail / Richmond, Rebecca C

BMC medicine

2023 Volume 21, Issue 1, Page(s) 350

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 ...

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.
MeSH term(s)	Female ; Humans ; Adiposity/genetics ; Menarche/genetics ; Mendelian Randomization Analysis ; Menopause/genetics ; Obesity
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-023-03051-x
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Article ; Online: Investigating causality in the association between DNA methylation and type 2 diabetes using bidirectional two-sample Mendelian randomisation.

Juvinao-Quintero, Diana L / Sharp, Gemma C / Sanderson, Eleanor C M / Relton, Caroline L / Elliott, Hannah R

Diabetologia

2023 Volume 66, Issue 7, Page(s) 1247–1259

Abstract: Aims/hypothesis: Several studies have identified associations between type 2 diabetes and DNA methylation (DNAm). However, the causal role of these associations remains unclear. This study aimed to provide evidence for a causal relationship between DNAm ...

Abstract	Aims/hypothesis: Several studies have identified associations between type 2 diabetes and DNA methylation (DNAm). However, the causal role of these associations remains unclear. This study aimed to provide evidence for a causal relationship between DNAm and type 2 diabetes. Methods: We used bidirectional two-sample Mendelian randomisation (2SMR) to evaluate causality at 58 CpG sites previously detected in a meta-analysis of epigenome-wide association studies (meta-EWAS) of prevalent type 2 diabetes in European populations. We retrieved genetic proxies for type 2 diabetes and DNAm from the largest genome-wide association study (GWAS) available. We also used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) when associations of interest were not available in the larger datasets. We identified 62 independent SNPs as proxies for type 2 diabetes, and 39 methylation quantitative trait loci as proxies for 30 of the 58 type 2 diabetes-related CpGs. We applied the Bonferroni correction for multiple testing and inferred causality based on p<0.001 for the type 2 diabetes to DNAm direction and p<0.002 for the opposing DNAm to type 2 diabetes direction in the 2SMR analysis. Results: We found strong evidence of a causal effect of DNAm at cg25536676 (DHCR24) on type 2 diabetes. An increase in transformed residuals of DNAm at this site was associated with a 43% (OR 1.43, 95% CI 1.15, 1.78, p=0.001) higher risk of type 2 diabetes. We inferred a likely causal direction for the remaining CpG sites assessed. In silico analyses showed that the CpGs analysed were enriched for expression quantitative trait methylation sites (eQTMs) and for specific traits, dependent on the direction of causality predicted by the 2SMR analysis. Conclusions/interpretation: We identified one CpG mapping to a gene related to the metabolism of lipids (DHCR24) as a novel causal biomarker for risk of type 2 diabetes. CpGs within the same gene region have previously been associated with type 2 diabetes-related traits in observational studies (BMI, waist circumference, HDL-cholesterol, insulin) and in Mendelian randomisation analyses (LDL-cholesterol). Thus, we hypothesise that our candidate CpG in DHCR24 may be a causal mediator of the association between known modifiable risk factors and type 2 diabetes. Formal causal mediation analysis should be implemented to further validate this assumption.
MeSH term(s)	Child ; Humans ; DNA Methylation/genetics ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Longitudinal Studies ; Genome-Wide Association Study ; Cholesterol
Chemical Substances	Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2023-05-19
Publishing country	Germany
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-023-05914-7
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Article ; Online: Paternal impact on the life course development of obesity and type 2 diabetes in the offspring.

Sharp, Gemma C / Lawlor, Debbie A

Diabetologia

2019 Volume 62, Issue 10, Page(s) 1802–1810

Abstract: The aetiologies of obesity and type 2 diabetes are incredibly complex, but the potential role of paternal influences remains relatively understudied. A better understanding of paternal influences on offspring risk of obesity and type 2 diabetes could ... ...

Abstract	The aetiologies of obesity and type 2 diabetes are incredibly complex, but the potential role of paternal influences remains relatively understudied. A better understanding of paternal influences on offspring risk of obesity and type 2 diabetes could have profound implications for public health, clinical practice and society. In this review, we outline potential biological and social mechanisms through which fathers might exert an impact on the health of their offspring. We also present a systematically compiled overview of the current evidence linking paternal factors to offspring development of obesity and type 2 diabetes throughout the life course. Although evidence is accumulating to support paternal associations with offspring outcomes, more high-quality research is needed to overcome specific methodological challenges and provide stronger causal evidence.
MeSH term(s)	Animals ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Epigenesis, Genetic/genetics ; Humans ; Obesity/genetics ; Obesity/pathology ; Paternal Inheritance/genetics ; Paternal Inheritance/physiology
Language	English
Publishing date	2019-08-27
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-019-4919-9
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Article ; Online: The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities.

Sharp, Gemma C / Fraser, Abigail / Sawyer, Gemma / Kountourides, Gabriella / Easey, Kayleigh E / Ford, Gemma / Olszewska, Zuzanna / Howe, Laura D / Lawlor, Deborah A / Alvergne, Alexandra / Maybin, Jacqueline A

International journal of epidemiology

2021 Volume 51, Issue 3, Page(s) 691–700

MeSH term(s)	COVID-19 ; Female ; Humans ; Menstrual Cycle ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-12-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187909-1
ISSN	1464-3685 ; 0300-5771
ISSN (online)	1464-3685
ISSN	0300-5771
DOI	10.1093/ije/dyab239
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Article ; Online: Epigenetics and noncommunicable diseases.

Sharp, Gemma C / Relton, Caroline L

Epigenomics

2017 Volume 9, Issue 6, Page(s) 789–791

MeSH term(s)	Epigenesis, Genetic ; Epigenomics/methods ; Genetic Predisposition to Disease ; Humans ; Noncommunicable Diseases ; Prognosis
Language	English
Publishing date	2017-05-19
Publishing country	England
Document type	Editorial
ZDB-ID	2537199-X
ISSN	1750-192X ; 1750-1911
ISSN (online)	1750-192X
ISSN	1750-1911
DOI	10.2217/epi-2017-0045
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Article ; Online: The relationships between women's reproductive factors: a Mendelian randomisation analysis.

Prince, Claire / Sharp, Gemma C / Howe, Laura D / Fraser, Abigail / Richmond, Rebecca C

BMC medicine

2022 Volume 20, Issue 1, Page(s) 103

Abstract: Background: Women's reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely ... ...

Abstract	Background: Women's reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors. Methods: We used data from the UK Biobank and genetic consortia with data available for the following 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. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap. Results: LDSC indicated that most reproductive factors are genetically correlated (r Conclusion: This study presents evidence that women's reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman's entire reproductive history, including the causal interplay between reproductive factors.
MeSH term(s)	Age Factors ; Child ; Female ; Humans ; Menarche/genetics ; Mendelian Randomization Analysis/methods ; Menopause/genetics ; Parturition ; Pregnancy ; Reproductive History ; Risk Factors
Language	English
Publishing date	2022-03-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-022-02293-5
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