Genetic and Environmental Influences on Body‐Fat Measures among African‐American Twins

Objective: To investigate the genetic and environmental influences on body‐fat measures including waist circumference (WC), waist‐to‐hip ratio (WHR), and body mass index (BMI) among African‐American men and women. Research Methods and Procedures: Measurements were taken as part of the Carolina African American Twin Study of Aging. This sample currently comprises 146 same‐sex African‐American twins with an average age of 50 years (range, 22 to 88 years). This analysis included 26 monozygotic and 29 dizygotic men and 45 monozygotic and 46 dizygotic women. Maximum likelihood quantitative genetic analysis was used. Results: In men, additive genetic effects accounted for 77% of the variance in WC, 59% in WHR, and 89% in BMI. In women, additive genetic effects accounted for 76% of the variance in WC, 56% in WHR, and 73% in BMI. The remaining variance in both men and women was attributed to unique environmental effects (WC, 21%; WHR, 36%; BMI, 11% in men and WC, 22%; WHR, 38%; BMI, 27% in women) and age (WC, 2%; WHR, 5% in men and WC, 2%; WHR, 6% in women). When BMI was controlled in the analysis of WC and WHR, it accounted for a portion of the genetic and environmental variance in WHR and over one‐half of the genetic and environmental variance in WC. Discussion: There are both genetic and environmental influences on WC, WHR, and BMI, and independent of BMI, there are genetic and environmental effects on WC and WHR among both genders. The results from this African‐American twin sample are similar to findings among white twin samples.     

Effects of HFE C282Y and H63D polymorphisms and polygenic background on iron stores in a large community sample of twins

The aim of this study was to assess and to compare the role of HFE polymorphisms and other genetic factors in variation in iron stores. Blood samples were obtained from 3,375 adult male and female twins (age range 29-82 years) recruited from the Australian Twin Registry. There were 1,233 complete pairs (562 monozygotic and 571 dizygotic twins). Serum iron, transferrin, transferrin saturation with iron, and ferritin were measured, and the HFE C282Y and H63D genotypes were determined. The frequency of the C282Y allele was.072, and that of the H63D allele was.141. Significant sources of variation in the indices of iron status included age, sex, age-sex interaction, body-mass index, and both the C282Y and H63D genotypes. The iron, transferrin, and saturation values of CC and CY subjects differed significantly, but the ferritin values did not. After correction for age and body-mass index, 23% and 31% of the variance in iron, 66% and 49% of the variance in transferrin, 33% and 47% of the variance in transferrin saturation, and 47% and 47% of the variance in ferritin could be explained by additive genetic factors, for men and women, respectively. HFE C282Y and H63D variation accounted for <5% of the corrected phenotypic variance, except for saturation (12% in women and 5% in men). We conclude that HFE CY and HD heterozygotes differ in iron status from the CC and HH homozygotes and that serum transferrin saturation is more affected than is serum ferritin. There are highly significant effects of other as-yet-unidentified genes on iron stores, in addition to HFE genotype.     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809–822, 2001)     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809-822, 2001)     

The epidemiology and genetics of smoking initiation and persistence: crosscultural comparisons of twin study results.

We examined whether there are crosscultural differences in the magnitude of genetic and environmental contributions to risk of becoming a regular smoker and of persistence in smoking in men and women. Standard methods of epidemiologic and genetic analysis were applied to questionnaire data on history of cigarette use obtained from large samples of male and female like-sex twins from three different countries: Australia (N = 2284 pairs), Sweden (N = 8651 pairs), and Finland (N = 10,948 pairs). Samples were subdivided into three age groups (AG), 18-25 years, 26-35 years, and 36-46 years of age. The magnitude of genetic influence for lifetime smoking was found to be consistent across country and AG for women (46%) and men (57%), and estimates of the contribution from environmental influences shared by twin and co-twin could be equated across all countries by AG for the women (from youngest to oldest AG: 45%, 35%, and 26%), but not for men, with separate estimates obtained for the Scandinavian (33%, 29%, and 19%) and the Australian men (26%, 9%, and 11%). There was no evidence for an important role for shared environmental influences on persistent smoking, and the genetic contribution was found to be consistent in magnitude in men and women, and the same across country and AG (52%). There are strong genetic influences on smoking behavior, and that risk of becoming a smoker (but not persistence in smoking) may be modified by experiences shared by twins that differ by AG and, at least for men, cultural background.     

The heritability of human longevity: A population-based study of 2872 Danish twin pairs born 1870–1900

The aim of this study was to explore, in a large and non-censored twin cohort, the nature (i.e., additive versus non-additive) and magnitude (i.e., heritability) of genetic influences on inter-individual differences in human longevity. The sample comprised all identified and traced non-emigrant like-sex twin pairs born in Denmark during the period 1870–1900 with a zygosity diagnosis and both members of the pairs surviving the age of 15 years. A total of 2872 pairs were included. Age at death was obtained from the Danish Central Person Register, the Danish Cause-of-Death Register and various other registers. The sample was almost non-censored on the date of the last follow-up (May 1, 1994), all but 0.6% had died, leaving a total of 2872 pairs for analysis. Proportions of variance attributable to genetic and environmental factors were assessed from variance-covariance matrices using the structural equation model approach. The most parsimonious explanation of the data was provided by a model that included genetic dominance (non-additive genetic effects caused by interaction within gene loci) and non-shared environmental factors (environmental factors that are individual-specific and not shared in a family). The heritability of longevity was estimated to be 0.26 for males and 0.23 for females. The small sex-difference was caused by a greater impact of non-shared environmental factors in the females. Heritability was found to be constant over the three 10-year birth cohorts included. Thus, longevity seems to be only moderately heritable. The nature of genetic influences on longevity is probably non-additive and environmental influences non-shared. There is no evidence for an impact of shared (family) environment.     

The genetic and environmental effects on depressive symptoms among older female twins.

The aim of the present study was to examine the contribution of genetic and environmental factors to depressive symptoms among older women. The participants were 102 monozygotic and 115 dizygotic female twin pairs aged 64 to 76 years. Depressive symptoms were assessed by the Center for the Epidemiologic Studies Depression Scale. The contribution of genetic and environmental effects was estimated for the constructed depressiveness factor and for the subscales which were depressed mood, psychomotor retardation, lack of wellbeing and interpersonal difficulties. Of the variance in depressiveness, shared environmental influences accounted for 39% and nonshared environmental influences 61%. For the subscales, 24% to 62% of the variance was explained by individual, and 13% to 23% by shared, environmental factors. Lack of wellbeing had its own moderate additive genetic effect explaining 30% of the variance. This study showed that in older women predominantly environmental factors underlay individual differences in depressiveness; however, the factors varied to some extent between dimensions measured by the subscales.     

Determinants of variation in plasma alkaline phosphatase activity: a twin study

Plasma alkaline phosphatase activity has been measured in 204 pairs of twins aged 18-34. Estimated genetic variance was the same in men and women, after exclusion of the youngest men, but environmental variance was greater in men so that the heritability was .90 +/- .02 in the women and .71 +/- .05 in the 19-34-year-old men. About 15% of the genetic variance was associated with the ABO blood group polymorphism, which is known to affect intestinal alkaline phosphatase. Differences in plasma alkaline phosphatase activity between normal people may be mainly due to genetically determined proportions of isoenzymes of differing stability.     

Genetic and non-genetic factors affecting birth-weight and adult Body Mass Index.

Birthweight affects neonatal mortality and morbidity and has been used as a marker of foetal undernutrition in studies of prenatal effects on adult characteristics. It is potentially influenced by genetic and environmental influences on the mother, and effects of foetal genotype, which is partially derived from the maternal genotype. Interpretations of variation in birthweight and associated characteristics as being due to prenatal environment ignore other possible modes of materno-foetal transmission. Subjects were adult twins recruited through the Australian Twin Registry, aged 17 to 87 years, and the sample comprised 1820 men and 4048 women. Twins reported their own birthweight as part of a health questionnaire. Body Mass Index (BMI) was calculated from self-reports of height and weight. Correlations between co-twins' birthweights were high for both monozygotic (r = 0.77) and dizygotic (r = 0.67) pairs, leading to substantial estimates of shared environmental effects (56% of variance) with significant additive genetic (23%) and non-shared environmental (21%) components. Adult BMI was mainly influenced by genetic factors, both additive (36% of variance) and nonadditive (35%). The correlation between birthweight and BMI was positive, in that heavier babies became on average more obese adults. A bivariate model of birthweight and adult BMI showed significant positive genetic (r(g) = 0.16, p = 0.005) and environmental (r(e) = 0.08, p = 0.000011) correlations. Intra-uterine environmental or perinatal influences shared by cotwins exercise a strong influence on birthweight, but the factors which affect both birthweight and adult BMI are partly genetic and partly non-shared environmental.     

Genetic study of the height and weight process during infancy.

Longitudinal height and weight data from 4649 Dutch twin pairs between birth and 2.5 years of age were analyzed. The data were first summarized into parameters of a polynomial of degree 4 by a mixed-effects procedure. Next, the variation and covariation in the parameters of the growth curve (size at one year of age, growth velocity, deceleration of growth, rate of change in deceleration [i.e., jerk] and rate of change in jerk [i.e., snap]) were decomposed into genetic and nongenetic sources. Additionally, the variation in the estimated size at birth and at 2 years of age interpolated from the polynomial was decomposed into genetic and nongenetic components. Variation in growth was best characterized by a genetic model which included additive genetic, common environmental and specific environmental influences, plus effects of gestational age. The effect of gestational age was largest for size at birth, explaining 39% of the variance. The differences between monozygotic and dizygotic twin correlations were largest for size at 1 and 2 years of age and growth velocity of weight, which suggests that these parameters are more influenced by heritability than size at birth, deceleration and jerk. The percentage of variance explained by additive genetic influences for height at 2 years of age was 52% for females and 58% for males. For weight at 2 years of age, heritability was approximately 58% for both sexes. Variation in snap height for males was also mainly influenced by additive genetic factors, while snap for females was influenced by both additive genetic and common environmental factors. The correlations for the additive genetic and common environmental factors for deceleration and snap are large, indicating that these parameters are almost entirely under control of the same additive genetic and common environmental factors. Female jerk and snap, and also female height at birth and height at 2 years of age, are mostly under control of the same additive genetic factor.     

Heritability of human brain functioning as assessed by electroencephalography.

To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilites for the delta, theta, alpha and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans.     

Genetic and Environmental Contributions to BMI in Adolescent and Young Adult Women

The objective of this study was to determine the genetic and environmental contributions to variation in BMI over time in European‐American (EA) and African‐American (AA) adolescent and young adult women. Self‐reported BMI (kg/m²) data from 2,816 EA (1,306 twin pairs, 56.5% monozygotic (MZ)) and 404 AA (178 twin pairs, 42.7% MZ) women at baseline (T1; median age 15 years) and 3,225 EA (1,511 twin pairs, 55.3% MZ) and 539 AA (252 pairs, 43.3% MZ) women at follow‐up (T2; median age 22 years) from a Midwestern US, population‐based twin registry were used to construct biometrical genetic models. For EA women, the majority of the variance in BMI was attributable to additive genetic effects at both time points (82% for each), with the remaining variance attributable to nonshared environment. Genetic and nonshared environment correlations between adolescent and young adult BMI were 0.87 and 0.23, respectively. Among AA women, nonadditive genetic effects comprised 68% of the variance at T1 and 73% at T2, and were highly correlated (r_D = 0.94). The proportions of variance attributable to nonshared environment at T1 (29%) and T2 (25%) were more modestly correlated (r_E = 0.31). The remaining variance in AA women could be attributed to additive genetic effects. Additive vs. nonadditive genetic effects contribute differentially to BMI in AA vs. EA adolescent and young adult women. Additional research is needed to better characterize the environmental and genetic factors related to BMI in persons of different races to aid understanding of the complex determinants of body weight in individuals.     

Why Some Women Look Young for Their Age

The desire of many to look young for their age has led to the establishment of a large cosmetics industry. However, the features of appearance that primarily determine how old women look for their age and whether genetic or environmental factors predominately influence such features are largely unknown. We studied the facial appearance of 102 pairs of female Danish twins aged 59 to 81 as well as 162 British females aged 45 to 75. Skin wrinkling, hair graying and lip height were significantly and independently associated with how old the women looked for their age. The appearance of facial sun-damage was also found to be significantly correlated to how old women look for their age and was primarily due to its commonality with the appearance of skin wrinkles. There was also considerable variation in the perceived age data that was unaccounted for. Composite facial images created from women who looked young or old for their age indicated that the structure of subcutaneous tissue was partly responsible. Heritability analyses of the appearance features revealed that perceived age, pigmented age spots, skin wrinkles and the appearance of sun-damage were influenced more or less equally by genetic and environmental factors. Hair graying, recession of hair from the forehead and lip height were influenced mainly by genetic factors whereas environmental factors influenced hair thinning. These findings indicate that women who look young for their age have large lips, avoid sun-exposure and possess genetic factors that protect against the development of gray hair and skin wrinkles. The findings also demonstrate that perceived age is a better biomarker of skin, hair and facial aging than chronological age.     

DIURNAL PREFERENCE AND SLEEP QUALITY: SAME GENES? A STUDY OF YOUNG ADULT TWINS

The aims of this study were to examine the genetic and environmental influences on diurnal preference and sleep quality, the association between these phenotypes, the genetic and environmental influences on this association, and the magnitude of overlap between these influences. Using a twin design, data on diurnal preference (measured by the Morningness-Eveningness Questionnaire) and sleep quality (measured by the Pittsburgh Sleep Quality Index) were collected from 420 monozygotic twins, 773 dizygotic twins, and 329 siblings (mode age?=?20 yrs, range?=?18–27 yrs) from a population-based twin registry across the UK. Univariate analyses indicated that dominance genetic influence accounted for 52% and non-shared environment 48% of variance in diurnal preference. For sleep quality, additive genetic influence explained 43% and non-shared environment 57% of the variance. The bivariate analysis indicated a significant association between greater eveningness preference and poorer sleep quality (r?=?.27). There was substantial overlap in the additive genetic influences on both phenotypes (rA?=?.57), and overlap in the dominance genetic influences common to both phenotypes was almost absolute (rD = .99). Overlap in non-shared environment was much smaller (rE?=?.02). Additive genetic influence accounted for 2% of the association, dominance genetic influence accounted for 94%, and non-shared environmental influences accounted for the remaining 4%. The substantial overlap in genetic influence between these phenotypes indicates that similar genes are important for diurnal preference and sleep quality. Therefore, those genes already known to influence one phenotype may be possible candidates to explore with regards to the other phenotype. (Author correspondence: ps701nh@gold.ac.uk)     

Parent ratings of temperament in twins: explaining the 'too low' DZ correlations.

Twin studies of child temperament using objective measures consistently suggest moderate heritability for most dimensions. However, parent rating measures produce unusual patterns of results. Intraclass correlations for identical (MZ) twins are typically high, whereas fraternal (DZ) twin intraclass correlations are much lower than would be predicted from an additive genetic model. The 'too low' DZ correlations can be explained by parent-rating biases that either exaggerate the differences between DZ twins (contrast effects) or that inflate the similarity of MZ twins (assimilation effects), or by the presence of non-additive genetic variance. To evaluate the three possible explanations, we used model-fitting procedures applied to parent-rating data averaged across 14, 20, 24, and 36 months of age in a sample of 196 twin pairs participating in the MacArthur Longitudinal Twin Study. The data were best described by a model that included contrast effects. Implications for non-twin research are discussed.     

Education modifies genetic and environmental influences on BMI

Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height(2)) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were -.13 in women, -.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity.     

Contribution of genetic and environmental effects to postural balance in older female twins.

The aim of the present study was to determine the relative roles of genetic and environmental influences on postural balance in older women. The participants were 97 monozygotic (MZ) and 102 dizygotic (DZ) female twins, aged 64-76 yr. Postural sway was measured during side-by-side stance with eyes open and eyes closed, and during semitandem stance with eyes open on a force platform. Sway data were condensed into four first-order and one second-order latent factors. The second-order factor, named balance, incorporates sway data from multiple tests and thus best describes the phenotype of postural balance. The contribution of genetic and environmental influences on the variability of the latent factors was assessed by using structural equation modeling. Additive genetic influences accounted for 35% and shared environmental influences accounted for 24% of the total variance in the balance factor. In the present study, postural balance in older women had a moderate genetic component. Genetic influences on postural balance may be mediated through gene variation in the systems that control posture. The finding that individual environmental influences accounted for almost one-half of the variance in postural balance points to the potential of targeted interventions to maintain and improve balance control in older persons.     

Investigating the genetic and environmental structure of Cloninger's personality dimensions in adolescence.

In this study we examined the genetic and environmental structure of four dimensions from Cloninger's personality system: novelty-seeking (NS), harm-avoidance (HA), reward-dependence (RD), and persistence (PS). Although adult twin studies suggest that these personality dimensions are moderately heritable, this is the first twin study of Cloninger's personality dimensions in adolescence--a period marked by significant physiological and social changes. Study participants included 1851 adolescent twins between the ages of 11 and 18 years; 878 complete twin pairs and 95 singleton-responding twins. Subjects were participants in two community-based samples of twins residing in the state of Colorado. Results indicated that cross-sectional mean levels for NS, HA and RD tended to show modest increases across the adolescent years, while PS showed modest mean decreases. Consistent sex differences in means were found only for RD. Univariate biometrical twin models were used to decompose trait variance into genetic and environmental sources. Results indicated that for NS, HA and RD additive genetic influences and unique environmental effects were sufficient to explain the data. PS, however, could be explained by unique and common environmental effects only, with different patterns of common environmental effects for males and females. We found moderate heritability estimates for NS, HA and RD ranging from .28 to .36--with no evidence for sex-limitation in those influences.     

Outlook for survivors of childhood in sub-Saharan Africa: adult mortality in Tanzania. Adult Morbidity and Mortality Project.

OBJECTIVE--To measure age and sex specific mortality in adults (15-59 years) in one urban and two rural areas of Tanzania. DESIGN--Reporting of all deaths occurring between 1 June 1992 and 31 May 1995. SETTING--Eight branches in Dar es Salaam (Tanzania''s largest city), 59 villages in Morogoro rural district (a poor rural area), and 47 villages in Hai district (a more prosperous rural area). SUBJECTS--40,304 adults in Dar es Salaam, 69,964 in Hai, 50,465 in Morogoro rural. MAIN OUTCOME MEASURES--Mortality and probability of death between 15 and 59 years of age (45Q15). RESULTS--During the three year observation period a total of 4929 deaths were recorded in adults aged 15-59 years in all areas. Crude mortalities ranged from 6.1/1000/year for women in Hai to 15.9/1000/year for men in Morogoro rural. Age specific mortalities were up to 43 times higher than rates in England and Wales. Rates were higher in men at all ages in the two rural areas except in the age group 25 to 29 years in Hai and 20 to 34 years in Morogoro rural. In Dar es Salaam rates in men were higher only in the 40 to 59 year age group. The probability of death before age 60 of a 15 year old man (45Q15) was 47% in Dar es Salaam, 37% in Hai, and 58% in Morogoro; for women these figures were 45%, 26%, and 48%, respectively. (The average 45Q15s for men and women in established market economies are 15% and 7%, respectively.) CONCLUSION--Survivors of childhood in Tanzania continue to show high rates of mortality throughout adult life. As the health of adults is essential for the wellbeing of young and old there is an urgent need to develop policies that deal with the causes of adult mortality.     

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

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.