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Causes of blood methylomic variation for middle-aged women measured by the HumanMethylation450 array.

ABSTRACT: To address the limitations in current classic twin/family research on the genetic and/or environmental causes of human methylomic variation, we measured blood DNA methylation for 479 women (mean age 56 years) including 66 monozygotic (MZ), 66 dizygotic (DZ) twin pairs and 215 sisters of twins, and 11 random technical duplicates using the HumanMethylation450 array. For each methylation site, we estimated the correlation for pairs of duplicates, MZ twins, DZ twins, and siblings, fitted variance component models by assuming the variation is explained by genetic factors, by shared and individual environmental factors, and by independent measurement error, and assessed the best fitting model. We found that the average (standard deviation) correlations for duplicate, MZ, DZ, and sibling pairs were 0.10 (0.35), 0.07 (0.21), -0.01 (0.14) and -0.04 (0.07). At the genome-wide significance level of 10-7, 93.3% of sites had no familial correlation, and 5.6%, 0.1%, and 0.2% of sites were correlated for MZ, DZ, and sibling pairs. For 86.4%, 6.9%, and 7.1% of sites, the best fitting model included measurement error only, a genetic component, and at least one environmental component. For the 13.6% of sites influenced by genetic and/or environmental factors, the average proportion of variance explained by environmental factors was greater than that explained by genetic factors (0.41 vs. 0.37, P value <10-15). Our results are consistent with, for middle-aged woman, blood methylomic variation measured by the HumanMethylation450 array being largely explained by measurement error, and more influenced by environmental factors than by genetic factors.

SUBMITTER: Li S

PROVIDER: S-EPMC5788416 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Causes of blood methylomic variation for middle-aged women measured by the HumanMethylation450 array.

Li Shuai S Wong Ee Ming EM Nguyen Tuong L TL Joo Ji-Hoon Eric JE Stone Jennifer J Dite Gillian S GS Giles Graham G GG Saffery Richard R Southey Melissa C MC Hopper John L JL

Epigenetics 20170101 11

To address the limitations in current classic twin/family research on the genetic and/or environmental causes of human methylomic variation, we measured blood DNA methylation for 479 women (mean age 56 years) including 66 monozygotic (MZ), 66 dizygotic (DZ) twin pairs and 215 sisters of twins, and 11 random technical duplicates using the HumanMethylation450 array. For each methylation site, we estimated the correlation for pairs of duplicates, MZ twins, DZ twins, and siblings, fitted variance co ...[more]

PMID: 29099274

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Project description:Physical activity improves health and may delay the onset of several chronic diseases. For women in particular, the rate of these diseases accelerates at middle age; therefore it is important to identify the determinants of health-enhancing physical activity during midlife in this population. In this study, we focused on determinants that are unique to the female sex, such as childbearing and menopause. The main objective was to characterize the level of physical activity and differences between active and inactive middle-aged Finnish women. In addition, we examined the association of physical activity with female reproductive factors at midlife. The study population consisted of 647 women aged 48 to 55 years who participated in our Estrogenic Regulation of Muscle Apoptosis (ERMA) study during the period from 2015 to 2016. Physical activity was measured objectively using hip-worn accelerometers for seven consecutive days. The outcome measures included the amounts of light intensity physical activity and moderate to vigorous intensity physical activity accumulated in bouts of at least 10 minutes (MVPA10). MVPA10 was used to determine whether women were placed in the active (≥150 min/week) or inactive (<150 min/week) group. Multiple linear regression models were performed with physical activity measures as dependent variables and cumulative reproductive history index, menopausal symptoms, and pelvic floor dysfunction as independent variables. We found that a large portion (61%) of Finnish middle-aged women did not meet the physical activity recommendations of 150 minutes of MVPA10 per week. In the studied cohort, 78% of women experienced menopausal symptoms, and 54% exhibited pelvic floor dysfunction. Perceived menopausal symptoms were associated with greater light physical activity. Perceived pelvic floor dysfunction was associated with lower MVPA10. According to the fully adjusted multiple linear regression models, reproductive factors explained 6.0% of the variation of MVPA10 and 7.5% of the variation of light physical activity. The results increase our knowledge of the factors related to physical activity participation among middle-aged women and indicate that menopausal symptoms and pelvic floor dysfunction should be identified and considered when promoting physical activity for women during midlife. The results emphasize that awareness of female reproductive factors, especially menopausal symptoms and pelvic floor dysfunction, is important for physical activity counseling to effectively help women in performing and sustaining health-enhancing amounts of physical activity. Specifically, the condition of the pelvic floor should be taken into account when identifying the proper activity type and intensity level so that health benefits of physical activity can still be attained without worsening symptoms.

Dataset Information

Causes of blood methylomic variation for middle-aged women measured by the HumanMethylation450 array.

Publications

Causes of blood methylomic variation for middle-aged women measured by the HumanMethylation450 array.

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