Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study

AbstractBackgroundDNA methylation is associated with body mass index (BMI), but it is not clear if methylation scores are biomarkers for extant BMI, or predictive of future BMI. Here we explore the causal nature and predictive utility of DNA methylation measured in peripheral blood with BMI and cardiometabolic traits.MethodsAnalyses were conducted across the life course using the ARIES cohort of mothers (n=792) and children (n=906), for whom DNA methylation and genetic profiles and BMI at multiple time points (3 in children at birth, in childhood and in adolescence, 2 in mothers during pregnancy and in middle age) were available. Genetic and DNA methylation scores for BMI were derived using published associations between BMI and DNA methylation and genotype. Causal relationships between methylation and BMI were assessed using Mendelian randomisation and cross-lagged models.ResultsThe DNA methylation scores in adult women explained 10% of extant BMI variance. However, less extant variance was explained by scores generated in the same women during pregnancy (2% BMI variance) and in older children (15-17 years; 3% BMI variance). Similarly, little extant variance was explained in younger children (at birth and at 7 years; 1% and 2%, respectively). These associations remained following adjustment for smoking exposure and education levels. The DNA methylation score was found to be a poor predictor of future BMI using linear and cross-lagged models, suggesting that DNA methylation variation does not cause later variation in BMI. However, there was some evidence to suggest that BMI is predictive of later DNA methylation. Mendelian randomisation analyses also support this direction of effect, although evidence is weak. Finally, we find that DNA methylation scores for BMI are associated with extant cardiometabolic traits independently of BMI and genetic score.ConclusionThe age-specific nature of DNA methylation associations with BMI, lack of causal relationship, and limited predictive ability of future BMI, indicate that DNA methylation is likely influenced by BMI and might more accurately be considered a biomarker of BMI and related outcomes than a predictor. Future epigenome-wide association studies may benefit from further examining associations between early DNA methylation and later health outcomes.

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STEROID RECEPTOR PHENOTYPE, EXPRESSION OF HER-2/NEU, PD-1, PD-L1 AND LYMPHOCYTIC-MACROPHAGAL INFILTRATION OF ENDOMETRIAL CARCINOMAS: COMPARISON OF MODERN MOLECULAR BIOLOGICAL TYPES OF THE DISEASE (THE ROLE OF BODY MASS INDEX)

Problems in oncology ◽

10.37469/0507-3758-2020-66-1-71-78 ◽

2020 ◽

Vol 66 (1) ◽

pp. 71-78

Author(s):

Lev Bershteyn ◽

Aleksandr Ivantsov ◽

Aglaya Ievleva ◽

A. Venina ◽

I. Berlev

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Tumor Tissue ◽

Immunohistochemical Analysis ◽

The Body ◽

Molecular Profile ◽

Total N ◽

Number Of Patients ◽

Her 2

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of >30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.

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Combination of sleep duration, TV time and body mass index is associated with cardiometabolic risk moderated by age in youth

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0399 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Ana P. Sehn ◽

Anelise R. Gaya ◽

Caroline Brand ◽

Arieli F. Dias ◽

Roya Kelishadi ◽

...

Keyword(s):

Body Mass Index ◽

Risk Factor ◽

Sleep Duration ◽

Body Mass ◽

Cardiometabolic Risk ◽

High Systolic Blood Pressure ◽

Television Time ◽

The Relationship ◽

Moderating Role

AbstractObjectivesThe combination of sleep duration, television (TV) time and body mass index (BMI) may be related to the alteration of cardiometabolic risk. However, there are few studies that use these variables grouped, and showing the moderating role of age. This study aimed to verify if the combination of sleep duration, TV time and BMI is associated with cardiometabolic risk and the moderating role of age in this relationship in youth.MethodsCross-sectional study conducted with 1411 adolescents (611 male), aged 10–17 years. Sleep duration, TV time and BMI were assessed and grouped into eight categories. Cardiometabolic risk was assessed by a continuous metabolic risk score, including the following variables: low HDL-cholesterol, elevated triglycerides, dysglycemia, high systolic blood pressure, high waist circumference and low cardiorespiratory fitness. Generalized linear models were used to test moderation of age in the relationship between the eight categories of sleep duration/television time/BMI with cardiometabolic risk.ResultsCardiometabolic risk factor showed association with all overweight or obesity independent of sleep time and TV time. Age moderated the relationship between sleep duration/television time/BMI with cardiometabolic risk. This association was stronger in younger adolescents (11 and 13 years), indicating that individuals with inadequate sleep, prolonged TV time and overweight/obesity present higher cardiometabolic risk values when compared to 15-year-old adolescents.ConclusionOverweight/obesity, independently of sleep duration and TV time, is the main risk factor for cardiometabolic disorders in adolescence. When moderated by age, younger adolescents that presented the combination of risk factors had higher cardiometabolic risk.

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