Adipocyte size and number have been suggested to predict the development of metabolic complications in obesity. However, the genetic and environmental determinants behind this phenomenon remain unclear.
We studied this question in rare-weight discordant (intra-pair difference (?) body mass index (BMI) 3-10 kg m(-2), n=15) and concordant (?BMI 0-2 kg m(-)(2), n=5) young adult (22-35 years) monozygotic twin pairs identified from 10 birth cohorts of Finnish twins (n=5 500 pairs). Subcutaneous abdominal adipocyte size from surgical biopsies was measured under a light microscope. Adipocyte number was calculated from cell size and total body fat (D ? A).
The concordant pairs were remarkably similar for adipocyte size and number (intra-class correlations 0.91-0.92, P
We examined how genotype-environment correlation processes differ as a function of adolescent age. We tested whether adolescent age moderates genetic and environmental influences on positivity and negativity in mother-adolescent and father-adolescent relationships using parallel samples of twin parents from the Twin and Offspring Study in Sweden and twin/sibling adolescents from the Nonshared Environment in Adolescent Development Study. We inferred differences in the role of passive and nonpassive genotype-environment correlation based on biometric moderation findings. The findings indicated that nonpassive gene-environment correlation played a stronger role for positivity in mother- and father-adolescent relationships in families with older adolescents than in families with younger adolescents, and that passive gene-environment correlation played a stronger role for positivity in the mother-adolescent relationship in families with younger adolescents than in families with older adolescents. Implications of these findings for the timing and targeting of interventions on family relationships are discussed.
To investigate the association between age-related macular degeneration (AMD) and mortality in older persons.
Population-based prospective cohort study.
Participants 67 to 96 years of age (43.1% male) enrolled between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study.
Retinal photographs of the macula were acquired digitally and evaluated for the presence of AMD lesions using the Wisconsin Age-Related Maculopathy grading scheme. Mortality was assessed prospectively through 2013 with cause of death available through 2009. The association between AMD and death, resulting from any cause and specifically cardiovascular disease (CVD), was examined using Cox proportional hazards regression with age as the time scale, adjusted for significant risk factors and comorbid conditions. To address a violation in the proportional hazards assumption, analyses were stratified into 2 groups based on the mean age at death (83 years).
Mortality resulting from all causes and CVD.
Among 4910 participants, after a median follow-up of 8.6 years, 1742 died (35.5%), of whom 614 (35.2%) had signs of AMD at baseline. Cardiovascular disease was the cause of death for 357 people who died before the end of 2009, of whom 144 (40%) had AMD (101 with early disease and 43 with late disease). After considering covariates, including comorbid conditions, having early AMD at any age or having late AMD in individuals younger than 83 years (n = 4179) were not associated with all-cause or CVD mortality. In individuals 83 years of age and older (n = 731), late AMD was associated significantly with increased risk of all-cause mortality (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.20-2.57) and CVD-related mortality (HR, 2.37; 95% CI, 1.41-3.98). In addition to having AMD, older individuals who died were more likely to be male and to have low body mass index, impaired cognition, and microalbuminuria.
Competing risk factors and concomitant conditions are important in determining mortality risk resulting from AMD. Individuals with early AMD are not more likely to die than peers of comparable age. Late AMD becomes a predictor of mortality by the mid-octogenarian years.
We tested the association between alcohol use disorder (AUD) and divorce; estimated the genetic and environmental influences on divorce; estimated how much genetic and environmental influences accounted for covariance between AUD and divorce; and estimated latent genetic and environmental correlations between AUD and divorce. We tested sex differences in these effects.
We identified twin and sibling pairs with AUD and divorce information in Swedish national registers. We described the association between AUD and divorce using tetrachorics and used twin and sibling models to estimate genetic and environmental influences on divorce, on the covariance between AUD and divorce and the latent genetic and environmental correlations between AUD and divorce.
A total of 670?836 individuals (53% male) born 1940-1965.
Life-time measures of AUD and divorce.
AUD and divorce were related strongly (males: rtet = +0.44, 95% CI = 0.43, 0.45; females rtet = +0.37, 95% CI = 0.36, 0.38). Genetic factors accounted for a modest proportion of the variance in divorce (males: 21.3%, 95% CI = 7.6, 28.5; females: 31.0%, 95% CI = 18.8, 37.1). Genetic factors accounted for most of the covariance between AUD and divorce (males: 52.0%, 95% CI = 48.8, 67.9; females: 53.74%, 95% CI = 17.6, 54.5), followed by non-shared environmental factors (males: 45.0%, 95% CI = 37.5, 54.9; females: 41.6%, 95% CI = 40.3, 60.2). Shared environmental factors accounted for a negligible proportion of the covariance (males: 3.0%, 95% CI = -3.0, 13.5; females: 4.75%, 95% CI = 0.0, 6.6). The AUD-divorce genetic correlations were high (males: rA = +0.76, 95% CI = 0.53, 0.90; females +0.52, 95% CI = 0.24, 0.67). The non-shared environmental correlations were modest (males: rE = +0.32, 95% CI = 0.31, 0.40; females: +0.27, 95% CI = 0.27, 0.36).
Divorce and alcohol use disorder are correlated strongly in the Swedish population, and the heritability of divorce is consistent with previous studies. Covariation between AUD and divorce results from overlapping genetic and non-shared environmental factors. Latent genetic and non-shared environmental correlations for alcohol use disorder and divorce are high and moderate.
The prospective cohort study design is ideal for examining diseases of public health importance, as its inherent temporal nature renders it advantageous for studying early life influences on health outcomes and research questions of aetiological significance. This paper will describe the development and characteristics of the All Our Babies (AOB) study, a prospective pregnancy cohort in Calgary, Alberta, Canada designed to examine determinants of maternal, infant, and child outcomes and identify barriers and facilitators in health care utilization.
Women were recruited from health care offices, communities, and through Calgary Laboratory Services before 25 weeks gestation from May 2008 to December 2010. Participants completed two questionnaires during pregnancy, a third at 4 months postpartum, and are currently being followed-up with questionnaires at 12, 24, and 36 months. Data was collected on pregnancy history, demographics, lifestyle, health care utilization, physical and mental health, parenting, and child developmental outcomes and milestones. In addition, biological/serological and genetic markers can be extracted from collected maternal and cord blood samples.
A total of 4011 pregnant women were eligible for recruitment into the AOB study. Of this, 3388 women completed at least one survey. The majority of participants were less than 35 years of age, Caucasian, Canadian born, married or in a common-law relationship, well-educated, and reported household incomes above the Calgary median. Women who discontinued after the first survey (n=123) were typically younger, non-Caucasian, foreign-born, had lower education and household income levels, were less likely to be married or in a common-law relationship, and had poor psychosocial health in early pregnancy. In general, AOB participants reflect the pregnant and parenting population at local and provincial levels, and perinatal indicators from the study are comparable to perinatal surveillance data.
The extensive and rich data collected in the AOB cohort provides the opportunity to answer complex questions about the relationships between biology, early experiences, and developmental outcomes. This cohort will contribute to the understanding of the biologic mechanisms and social/environmental pathways underlying associations between early and later life outcomes, gene-environment interactions, and developmental trajectories among children.
The extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA) were evaluated. Participants were 6,899 women from the Swedish Twin Study of Adults: Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the coexpression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN.
Cites: Arch Gen Psychiatry. 2005 Jun;62(6):593-60215939837
Clinically significant anxiety symptoms are prevalent among the elderly, yet knowledge about the longitudinal course of anxiety symptoms in later life remains scarce. The goals of this study were to (a) characterize age trajectories of state anxiety symptoms in the second half of life, and (b) estimate genetic and environmental contributions to individual differences in the age trajectory of state anxiety. This study was based on data from 1,482 participants in the Swedish Adoption/Twin Study of Aging who were aged 50 and older at their first occasion (512 complete twin pairs, 458 singletons) and had up to 6 measurement occasions spanning 11 years. Consistent with life span developmental theories of age-related emotional change, anxiety symptom levels declined during the transition from midlife to the mid-60s, followed by a mild increase that gradually plateaued in the 80s. There were substantial individual differences in the age trajectory of anxiety. After accounting for effects of sex, cohort, mode of testing, and proximity to death, this longitudinal variation was partitioned into biometric sources. Nonshared environmental variance was highest in the late 60s and declined thereafter, whereas genetic variance increased at an accelerated pace from approximately age 60 onward. There was no evidence for effects of rearing or other shared environment on anxiety symptoms in later life. These findings highlight how the etiology of anxiety symptoms changes from midlife to old age.
Cites: Twin Res Hum Genet. 2007 Jun;10(3):423-3317564500
Cites: Acta Genet Med Gemellol (Roma). 1991;40(1):7-201950353
Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P
Several recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness.
To examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs.
This study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design.
Maternal self-reported smoking during pregnancy, obtained from antenatal visits.
Severe mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders.
Of the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses.
This population- and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.