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Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success.

OBJECTIVE. To evaluate the associations of caffeinated, alcoholic and sweetened beverage intakes with antral follicle count (AFC), a well-accepted biomarker of ovarian reserve. DESIGN. Observational prospective cohort study. SETTING. Fertility center at an academic hospital. PATIENTS. This study includes 567 women seeking fertility care at the Massachusetts General Hospital who participated in the Environment and Reproductive Health Study. INTERVENTION. None. Women self-reported consumption of caffeinated (coffee, tea, soda), alcoholic (wine, beer, liquor), sugar-sweetened and artificially sweetened beverages using a validated food frequency questionnaire. MAIN OUTCOME MEASURE. AFC was assessed using a transvaginal ultrasound performed on the 3rd day of an unstimulated menstrual cycle or on the 3rd day of a progesterone withdrawal bleed. RESULTS. Median (interquartile range) age and AFC were 35.0 (32.0–38.0) years and 13.0 (9.0–18.0). Median (range) intake of caffeinated, alcoholic, sugar-sweetened and artificially sweetened beverages in servings/day were 1.08 (0–7.08), 0.35 (0–3.84), 0.04 (0–4.80) and 0.04 (0–7.50), respectively. All examined beverages were unrelated to AFC. The multivariable adjusted mean AFC (95% confidence interval) for women in the top and bottom quartiles of intake were 13.8 (13.0–14.7) and 13.8 (12.9–14.7) for caffeinated beverages; 13.8 (13.0–14.7) and 13.8 (13.0–14.6) for alcoholic beverages; 13.5 (12.6–14.4) and 13.3 (12.4–14.2) for sugar-sweetened beverages; and 13.2 (12.4–14.1) and 13.4 (12.6–14.3) for artificially sweetened beverages. CONCLUSION. Low-to-moderate intakes of caffeinated, alcoholic, sugar-sweetened and artificially sweetened beverages were unrelated to ovarian reserve, as measured by AFC, in a cohort of women seeking fertility care.

We aimed to determine whether intake of pesticide residues from fruits and vegetables was associated with glioma. Within 3 prospective cohorts from 1998–2016—the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow-up Study—we computed multivariable-adjusted hazard ratios (MVHRs) and 95% confidence intervals (CI) for glioma by quintiles of intake of low- and high-pesticide-residue fruits and vegetables using Cox proportional hazards regression. Fruits and vegetables were categorized as high or low residue using a validated method based on pesticide surveillance data. We confirmed 275 glioma cases across 2,745,862 person-years. A significant association was observed between intake of high-residue fruits and vegetables and glioma in NHS (MVHR = 2.99, 95% CI: 1.38, 6.44 comparing highest with lowest quintile, P for trend = 0.02). This was not identified in NHSII (MVHR = 0.52, 95% CI: 0.19, 1.45, P for trend = 0.20) or Health Professionals Follow-up Study (MVHR = 1.01, 95% CI: 0.42, 2.45, P for trend = 0.39). No significant associations were observed by intake of low-residue fruits and vegetables; overall intake was not significantly associated with glioma in any cohort. We found no evidence for an inverse relationship of fruit and vegetable intake with glioma. Although limited in power, this study suggests a possible association between fruit-and-vegetable pesticide residue intake and risk of glioma that merits further study.

Additional file 1. Figure S1: flow chart of Project Viva women included in this analysis.

Additional file 3.Table S2: Associations of lifetime breastfeeding duration (BFD) with dominant and nondominant handgrip strength among N=304 women who were nulliparous at enrollment.

Additional file 1: Table S1. Distributions of pregnancy outcomes by history of infertility for the index pregnancy (n = 2201). Table S2. Unadjusted and adjusted β coefficients for systolic blood pressure in women with vs. without infertility, excluding 39 women with PCOS. Table S3. Unadjusted and adjusted β coefficients for systolic blood pressure in women with vs. without infertility, according to the use of MAR and excluding 39 women with PCOS. Table S4. Unadjusted and adjusted β coefficients for systolic blood pressure in women with vs. without infertility, according to the use of MAR and type of medication, excluding 39 women with PCOS. Figure S1. Conceptual Directed Acyclic Graph depicting the variables under study.

Additional file 3.Table S2: Associations of lifetime breastfeeding duration (BFD) with dominant and nondominant handgrip strength among N=304 women who were nulliparous at enrollment.

Additional file 2. Table S1: Characteristics of Project Viva participants included vs excluded from this analysis.

Additional file 2. Table S1: Characteristics of Project Viva participants included vs excluded from this analysis.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

Supplemental material, sj-pdf-1-smm-10.1177_0962280220966019 for Development of a mixture model allowing for smoothing functions of longitudinal trajectories by Ming Ding, Jorge E. Chavarro and Garrett M. Fitzmaurice in Statistical Methods in Medical Research

Additional file 2. Show Cards Used in the EVESCAM Study.

Additional file 1. Dietary Intake Questionnaire.

Supplemental material, sj-pdf-1-smm-10.1177_0962280220966019 for Development of a mixture model allowing for smoothing functions of longitudinal trajectories by Ming Ding, Jorge E. Chavarro and Garrett M. Fitzmaurice in Statistical Methods in Medical Research

European Union under grant agreement 675526-REP-BIOTECH-H2020-MSCA-Innovative Training Networks-2015

Men diagnosed with nonmetastatic prostate cancer have a long life expectancy, and many die of unrelated causes. It is therefore important to know to what extent post-diagnostic diet may affect disease-specific and overall mortality. A total of 926 men participating in the Physicians' Health Study diagnosed with nonmetastatic prostate cancer completed diet questionnaires for a median of 5.1 years after diagnosis, and were followed thereafter to assess mortality for a median of 9.9 years since questionnaire completion. Two post-diagnostic dietary patterns were identified: a Prudent pattern, characterized by higher intake of vegetables, fruits, fish, legumes, and whole grains; and a Western pattern, characterized by higher intake of processed and red meats, high-fat dairy and refined grains. Cox regression was used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). During 8,093 person-years of follow-up, 333 men died, 56 (17%) of prostate cancer. The Western pattern was significantly related to a higher risk of prostate cancer-specific and all-cause mortality. Comparing men in the highest versus the lowest quartile of the Western pattern, the HRs were 2.53 (95% CI, 1.00-6.42; Ptrend = 0.02) for prostate cancer-specific mortality and 1.67 (95% CI, 1.16-2.42; Ptrend = 0.01) for all-cause mortality. The Prudent pattern was associated with a significantly lower all-cause mortality (HRQuartile 4 vs. Quartile 1: 0.64; 95% CI, 0.44-0.93; Ptrend = 0.02); the relationship with prostate cancer-specific mortality was inverse but not statistically significant. A post-diagnostic Western dietary pattern was associated with higher prostate cancer-specific and all-cause mortality, whereas a Prudent dietary pattern was related to lower all-cause mortality after prostate cancer diagnosis.

Introducción: En 2013 se informó de un recuento relativamente bajo de espermatozoides entre jóvenes universitarios del Sureste español. Además, se ha descrito una disminución en la concentración y conteo espermático durante las últimas décadas en el mundo occidental, y una de las causas potenciales podrían ser los cambios en los estilos de vida. Aunque es un tema controvertido, distintos estudios sugieren que la afectación de algunos parámetros seminales, tales como la movilidad o la morfología espermática, podrían estar asociados con niveles bajos de vitamina D. Objetivos: Analizar la asociación entre los parámetros seminales y los niveles séricos de hormonas reproductivas y la vitamina D [25(OH)D] en jóvenes españoles, así como examinar esta asociación en relación con la ingesta dietaria de Vitamina D. Material y método: Este estudio transversal incluye a 198 estudiantes universitarios reclutados entre 2010-2011 en el sur de España, que proporcionaron muestras de sangre, semen y cumplimentaron cuestionarios demográficos y sobre estilos de vida. La calidad del semen se evaluó midiendo el volumen, la concentración, el recuento total, la motilidad y la morfología espermática siguiendo las directrices de la Organización Mundial de la Salud (OMS). Las muestras de suero fueron analizadas para determinar el 25OHD total y las hormonas reproductivas FSH, LH, testosterona, inhibina B y estradiol. Los niveles de vitamina D sérica se agruparon en tres grupos, insuficiencia/deficiencia, adecuada y alto. La ingesta de vitamina D se evaluó mediante un cuestionario específico validado de frecuencia alimentaria. Las asociaciones entre los parámetros espermáticos y los niveles de hormonas reproductivas y la vitamina D se analizaron mediante regresión lineal múltiple y análisis de la covarianza (ANCOVA), ajustándose por posibles factores de confusión y otras covariables importantes. Resultados: Casi todos los varones presentaron niveles adecuados de vitamina D en suero. Sólo 3 varones (1,5%) tenían deficiencia de vitamina D (