Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Mid-life social participation and physical performance at age 60-64: evidence from the 1946 British Birth Cohort Study.

BACKGROUND: Previous studies linking social activity and disability have been limited by focussing on self-reported physical performance in older adults (>65). We examined whether social participation in mid-life is associated with objective and subjective measures of physical performance in older age. METHODS: Participants of the Medical Research Council National Survey of Health and Development reported their involvement in social activities at ages 43 and 60-64 years; frequency of such involvement was classified into thirds. Physical performance was measured at age 60-64 using: grip strength; standing balance; chair rises; timed get-up-and-go; self-reported physical function from the Short Form-36. Multivariable regression was used to examine longitudinal associations between social participation and each physical performance measure. We also investigated whether change in social participation between 43 and 60-64 was associated with each outcome. RESULTS: In fully adjusted models, higher frequency of social participation at 43 was associated with faster chair rise (1.42 repetitions/min, 95% CI 0.45-2.39) and timed get-up-and-go speed (2.47 cm/s, 95% CI 0.27-4.67) and lower likelihood of self-report limitations (OR of low physical function 0.67, 95% CI 0.50-0.91) at 60-64 compared with low frequency. Better performance in objectively measured outcomes was observed only if higher social participation persisted over time whereas lower odds of self-reported limitations were found in all groups when compared to those with persistently low participation (ORs 0.43-0.56, all P≤0.02). CONCLUSION: Our findings suggest that associations between higher levels of social participation in mid-life and better physical performance exist only if this social participation persists through to older age.

Socioeconomic inequalities in resilience and vulnerability among older adults: a population-based birth cohort analysis.

ABSTRACTBackground:Aging is associated with declines in physical capability; however, some individuals demonstrate high well-being despite this decline, i.e. they are "resilient." We examined socioeconomic position (SEP) and resilience and the influence of potentially modifiable behavioral resources, i.e. social support and leisure time physical activity (LTPA), on these relationships. METHODS: Data came from the Medical Research Council National Survey of Health and Development, a nationally-representative birth cohort study. Resilience-vulnerability at age 60-64 years (n = 1,756) was operationalized as the difference between observed and expected levels of well-being, captured by the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), given the level of performance-based physical capability. SEP was assessed by father's and own social class, parental education, and intergenerational social mobility. PA and structural/functional social support were reported at ages 53 years and 60-64 years. Path analysis was used to examine mediation of SEP and resilience-vulnerability through LTPA and social support. RESULTS: Participants in the highest social class had scores on the resilience to vulnerability continuum that were an average of 2.3 units (ß = 0.46, 95% CI 0.17, 0.75) higher than those in the lowest social class. Greater LTPA (ß = 0.58, 95% CI 0.31, 0.85) and social support (ß = 3.27, 95% CI 2.90, 3.63) were associated with greater resilience; LTPA partly mediated participant social class and resilience (23.4% of variance). CONCLUSIONS: Adult socioeconomic advantage was associated with greater resilience. Initiatives to increase LTPA may contribute to reducing socioeconomic inequalities in this form of resilience in later life.

A holistic approach to healthy ageing: how can people live longer, healthier lives?

BACKGROUND: Although lifespan is increasing, there is no evidence to suggest that older people are experiencing better health in their later years than previous generations. Nutrition, at all stages of life, plays an important role in determining health and wellbeing. METHODS: A roundtable meeting of UK experts on nutrition and ageing considered key aspects of the diet-ageing relationship and developed a consensus position on the main priorities for research and public health actions that are required to help people live healthier lives as they age. RESULTS: The group consensus highlighted the requirement for a life course approach, recognising the multifactorial nature of the impact of ageing. Environmental and lifestyle influences at any life stage are modified by genetic factors and early development. The response to the environment at each stage of life can determine the impact of lifestyle later on. There are no key factors that act in isolation to determine patterns of ageing and it is a combination of environmental and social factors that drives healthy or unhealthy ageing. Too little is known about how contemporary dietary patterns and sedentary lifestyles will impact upon healthy ageing in future generations and this is a priority for future research. CONCLUSIONS: There is good evidence to support change to lifestyle (i.e. diet, nutrition and physical) activity in relation to maintaining or improving body composition, cognitive health and emotional intelligence, immune function and vascular health. Lifestyle change at any stage of life may extend healthy lifespan, although the impact of early changes appears to be greatest.

Work-family life courses and BMI trajectories in three British birth cohorts.

BACKGROUND/OBJECTIVES: Combining work and family responsibilities has previously been associated with improved health in mid-life, yet little is known about how these associations change over time (both biographical and historical) and whether this extends to body mass index (BMI) trajectories for British men and women. The purpose of this study was to investigate relationships between work-family life courses and BMI trajectories across adulthood (16-42 years) for men and women in three British birth cohorts. SUBJECTS/METHODS: Multiply imputed data from three nationally representative British birth cohorts were used-the MRC National Survey of Health and Development (NSHD; 1946 birth cohort, n=3012), the National Child Development Study (NCDS; 1958 birth cohort, n=9614) and the British Cohort Study (BCS; 1970 birth cohort, n=8140). A typology of work-family life course types was developed using multi-channel sequence analysis, linking annual information on work, partnerships and parenthood from 16 to 42 years. Work-family life courses were related to BMI trajectories using multi-level growth models. Analyses adjusted for indicators of prior health, birthweight, child BMI, educational attainment and socioeconomic position across the life course, and were stratified by gender and cohort. RESULTS: Work-family life courses characterised by earlier transitions to parenthood and weaker long-term links to employment were associated with greater increases in BMI across adulthood. Some of these differences, particularly for work-family groups, which are becoming increasingly non-normative, became more pronounced across cohorts (for example, increases in BMI between 16 and 42 years in long-term homemaking women: NSHD: 4.35 kg m-2, 95% confidence interval (CI): 3.44, 5.26; NCDS: 5.53 kg m-2, 95% CI: 5.18, 5.88; BCS: 6.69 kg m-2, 95% CI: 6.36, 7.02). CONCLUSIONS: Becoming a parent earlier and weaker long-term ties to employment are associated with greater increases in BMI across adulthood in British men and women.

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study.

This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. INTRODUCTION: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. METHODS: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0-16 g) worn at the waist for 7 days were classified as low (0.5-1.0 g), medium (1.0-1.5 g) or higher (≥1.5 g) impacts. RESULTS: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [-0.02, 0.08]). CONCLUSIONS: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA.

Resilience measurement in later life: a systematic review and psychometric analysis.

OBJECTIVES: To systematically review and examine the psychometric properties of established resilience scales in older adults, i.e. ≥60 years. METHODS: A systematic review of Scopus and Web of Science databases was undertaken using the search strategy "resilience" AND (ageing OR aging)". Independent title/abstract and fulltext screening were undertaken, identifying original peer-reviewed English articles that conducted psychometric validation studies of resilience metrics in samples aged ≥60 years. Data on the reliability/validity of the included metrics were extracted from primary studies. RESULTS: Five thousand five hundred nine studies were identified by the database search, 426 used resilience psychometrics, and six psychometric analysis studies were included in the final analysis. These studies conducted analyses of the Connor Davidson Resilience Scale (CD-RISC) and its shortened 10-item version (CD-RISC10), the Resilience Scale (RS) and its shortened 5- (RS-5) and 11- (RS-11) item versions, and the Brief Resilient Coping Scale (BRCS). All scales demonstrated acceptable levels of internal consistency, convergent/discriminant validity and theoretical construct validity. Factor structures for the RS, RS-11 and CD-RISC diverged from the structures in the original studies. CONCLUSION: The RS, RS-5, RS-11, CD-RISC, CD-RISC10 and BRCS demonstrate psychometric robustness adequate for continued use in older populations. However, results from the current study and pre-existing theoretical construct validity studies most strongly support the use of the RS, with modest and preliminary support for the CD-RISC and BRCS, respectively. Future studies assessing the validity of these metrics in older populations, particularly with respect to factor structure, would further strengthen the case for the use of these scales.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Overweight across the life course and adipokines, inflammatory and endothelial markers at age 60-64 years: evidence from the 1946 birth cohort.

BACKGROUND/OBJECTIVES: There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age. SUBJECTS/METHODS: Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests. RESULTS: In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model. CONCLUSIONS: Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention.

Birth weight and growth from infancy to late adolescence in relation to fat and lean mass in early old age: findings from the MRC National Survey of Health and Development.

OBJECTIVE: High birth weight and greater weight gain in infancy have been associated with increased risk of obesity as assessed using body mass index, but few studies have examined associations with direct measures of fat and lean mass. This study examined associations of birth weight and weight and height gain in infancy, childhood and adolescence with fat and lean mass in early old age. SUBJECTS: A total of 746 men and 812 women in England, Scotland and Wales from the MRC National Survey of Health and Development whose heights and weights had been prospectively ascertained across childhood and adolescence and who had dual energy X-ray absorptiometry measures at age 60-64 years. METHODS: Associations of birth weight and standardised weight and height (0-2 (weight only), 2-4, 4-7, 7-11, 11-15, 15-20 years) gain velocities with outcome measures were examined. RESULTS: Higher birth weight was associated with higher lean mass and lower android/gynoid ratio at age 60-64 years. For example, the mean difference in lean mass per 1 standard deviation increase in birth weight was 1.54 kg in males (95% confidence interval=1.04, 2.03) and 0.78 kg in females (0.41, 1.14). Greater weight gain in infancy was associated with higher lean mass, whereas greater gains in weight in later childhood and adolescence were associated with higher fat and lean mass, and fat/lean and android/gynoid ratios. Across growth intervals greater height gain was associated with higher lean but not fat mass, and with lower fat/lean and android/gynoid ratios. CONCLUSION: Findings suggest that growth in early life may have lasting effects on fat and lean mass. Greater weight gain before birth and in infancy may be beneficial by leading to higher lean mass, whereas greater weight gain in later childhood and adolescence may be detrimental by leading to higher fat/lean and android/gynoid ratios.

Lifetime affect and midlife cognitive function: prospective birth cohort study.

BACKGROUND: Recurrent affective problems are predictive of cognitive impairment, but the timing and directionality, and the nature of the cognitive impairment, are unclear. AIMS: To test prospective associations between life-course affective symptoms and cognitive function in late middle age. METHOD: A total of 1668 men and women were drawn from the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort). Longitudinal affective symptoms spanning age 13-53 years served as predictors; outcomes consisted of self-reported memory problems at 60-64 years and decline in memory and information processing from age 53 to 60-64 years. RESULTS: Regression analyses revealed no clear pattern of association between longitudinal affective symptoms and decline in cognitive test scores, after adjusting for gender, childhood cognitive ability, education and midlife socioeconomic status. In contrast, affective symptoms were strongly, diffusely and independently associated with self-reported memory problems. CONCLUSIONS: Affective symptoms are more clearly associated with self-reported memory problems in late midlife than with objectively measured cognitive performance.

Adolescent conduct problems and premature mortality: follow-up to age 65 years in a national birth cohort.

BACKGROUND: Severe youth antisocial behaviour has been associated with increased risk of premature mortality in high-risk samples for many years, and some evidence now points to similar effects in representative samples. We set out to assess the prospective association between adolescent conduct problems and premature mortality in a population-based sample of men and women followed to the age of 65 years. METHOD: A total of 4158 members of the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort) were assessed for conduct problems at the ages of 13 and 15 years. Follow-up to the age of 65 years via the UK National Health Service Central Register provided data on date and cause of death. RESULTS: Dimensional measures of teacher-rated adolescent conduct problems were associated with increased hazards of death from cardiovascular disease by the age of 65 years in men [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.32], and of all-cause and cancer mortality by the age of 65 years in women (all-cause HR 1.16, 95% CI 1.07-1.25). Adjustment for childhood cognition and family social class did little to attenuate these risks. Adolescent conduct problems were not associated with increased risks of unnatural/substance-related deaths in men or women in this representative sample. CONCLUSIONS: Whereas previous studies of high-risk delinquent or offender samples have highlighted increased risks of unnatural and alcohol- or substance abuse-related deaths in early adulthood, we found marked differences in mortality risk from other causes emerging later in the life course among women as well as men.

Early development, stress and depression across the life course: pathways to depression in a national British birth cohort.

BACKGROUND: The aetiology of depression is multifactorial, with biological, cognitive and environmental factors across the life course influencing risk of a depressive episode. There is inconsistent evidence linking early life development and later depression. The aim of this study was to investigate relationships between low birthweight (LBW), infant neurodevelopment, and acute and chronic stress as components in pathways to depression in adulthood. METHOD: The sample included 4627 members of the National Survey of Health and Development (NSHD; the 1946 British birth cohort). Weight at birth, age of developmental milestones, economic deprivation in early childhood, acute stressors in childhood and adulthood, and socio-economic status (SES) in adulthood were assessed for their direct and indirect effects on adolescent (ages 13 and 15 years) and adult (ages 36, 43 and 53 years) measures of depressive symptoms in a structural equation modelling (SEM) framework. A structural equation model developed to incorporate all variables exhibited excellent model fit according to several indices. RESULTS: The path of prediction from birthweight to age of developmental milestones to adolescent depression/anxiety to adult depression/anxiety was significant (p < 0.001). Notably, direct paths from birthweight (p = 0.25) and age of developmental milestones (p = 0.23) to adult depression were not significant. Childhood deprivation and stressors had important direct and indirect effects on depression. Stressors in adulthood were strongly associated with adult depression. CONCLUSIONS: Depression in adulthood is influenced by an accumulation of stressors across the life course, including many that originate in the first years of life. Effects of early-life development on mental health appear by adolescence.

Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals.

AIMS/HYPOTHESIS: Genetic pleiotropy may contribute to the clustering of obesity and metabolic conditions. We assessed whether genetic variants that are robustly associated with BMI and waist-to-hip ratio (WHR) also influence metabolic and cardiovascular traits, independently of obesity-related traits, in meta-analyses of up to 37,874 individuals from six European population-based studies. METHODS: We examined associations of 32 BMI and 14 WHR loci, individually and combined in two genetic predisposition scores (GPSs), with glycaemic traits, blood lipids and BP, with and without adjusting for BMI and/or WHR. RESULTS: We observed significant associations of BMI-increasing alleles at five BMI loci with lower levels of 2 h glucose (RBJ [also known as DNAJC27], QPTCL: effect sizes -0.068 and -0.107 SD, respectively), HDL-cholesterol (SLC39A8: -0.065 SD, MTCH2: -0.039 SD), and diastolic BP (SLC39A8: -0.069 SD), and higher and lower levels of LDL- and total cholesterol (QPTCL: 0.041 and 0.042 SDs, respectively, FLJ35779 [also known as POC5]: -0.042 and -0.041 SDs, respectively) (all p < 2.4 × 10(-4)), independent of BMI. The WHR-increasing alleles at two WHR loci were significantly associated with higher proinsulin (GRB14: 0.069 SD) and lower fasting glucose levels (CPEB4: -0.049 SD), independent of BMI and WHR. A higher GPS-BMI was associated with lower systolic BP (-0.005 SD), diastolic BP (-0.006 SD) and 2 h glucose (-0.013 SD), while a higher GPS-WHR was associated with lower HDL-cholesterol (-0.015 SD) and higher triacylglycerol levels (0.014 SD) (all p < 2.9 × 10(-3)), independent of BMI and/or WHR. CONCLUSIONS/INTERPRETATION: These pleiotropic effects of obesity-susceptibility loci provide novel insights into mechanisms that link obesity with metabolic abnormalities.

The role of BMI across the life course in the relationship between age at menarche and diabetes, in a British Birth Cohort.

AIMS: Previous research showing an inverse association between age of menarche and adult diabetes relied on recalled age at menarche and did not adjust for BMI across the life course. We investigated the relationship between age at menarche and diabetes, and whether childhood, adolescent or adult BMI attenuates this relationship. METHODS: We used data from the Medical Research Council National Survey of Health and Development, a British birth cohort study of men and women born in 1946, with contemporaneous recording of the age of menarche, BMI at 2, 7, 15 and 20-53 years and diabetes status to 53 years. RESULTS: A significant inverse relationship between age at menarche and diabetes [hazard ratio = 0.73 per year older age at menarche (95% CI 0.56-0.96), P = 0.02] was attenuated by adjustment for adult BMI [hazard ratio 0.85 (95% CI 0.65-1.10), P = 0.2]. The effect of age at menarche on Type 2 diabetes was very similar to that for all types of diabetes. Attenuation of the association between age at menarche and diabetes was also observed with BMI at 15 years, but less so with BMI measured earlier in childhood. CONCLUSIONS: Earlier age at menarche is associated with a higher risk of diabetes, and specifically Type 2 diabetes, in later life, which is most strongly attenuated by adolescent and adult adiposity. Early menarche may be clinically useful in identifying women who are at risk of later adiposity and so of developing Type 2 diabetes.

A life course approach to healthy ageing: the HALCyon programme.

Healthy ageing across the life course (HALCyon) is an interdisciplinary research collaboration that harnesses the power of nine UK cohort studies to discover life course influences on physical and cognitive capability, social and psychological well-being, and underlying biology. In this symposium, HALCyon co-investigators reported the first wave of findings from five of the eight work packages.

Symptoms of depression and anxiety, and change in body mass index from adolescence to adulthood: results from a British birth cohort.

BACKGROUND: Depression and anxiety have been shown to be associated with obesity and underweight, but little is known about how the relationship varies across the life course, from adolescence through adulthood. We aimed to investigate the association between adolescent- and adult-onset affective symptoms and body mass index (BMI) change from age 15 to 53 years. METHOD: We used data from a British birth cohort born in 1946 and followed up ever since. The relationship between affective symptom profiles, distinguishing adolescent-onset and adult-onset symptoms, and BMI change from adolescence to age 53 years was investigated using multilevel models. RESULTS: Women with adolescent-onset symptoms had lower mean BMI at age 15 years, faster rates of increase across adulthood, and higher BMI at age 53 years than those with no symptoms. Men with adolescent-onset symptoms had lower BMI at all ages from 15 to 53 years. The BMI trajectories of men and women with adult-onset symptoms did not differ from those with absence of symptoms at all ages. CONCLUSIONS: The relationship between affective symptoms and change in BMI varies by sex and age at onset of symptoms. Adolescence may be an important period for the development of the association between affective symptoms and weight gain in girls. Intervention to prevent increases in BMI across adult life in women with adolescent-onset symptoms, even if they are not overweight at this age, should be considered.

Factors associated with symptoms of anxiety and depression in five cohorts of community-based older people: the HALCyon (Healthy Ageing across the Life Course) Programme.

BACKGROUND: Symptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety. METHOD: We used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme: the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each. RESULTS: Greater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life. CONCLUSIONS: Anxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed.

Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

BACKGROUND: Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. METHOD: A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). RESULTS: Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. CONCLUSION: This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Alcohol intake and risk of colorectal cancer: results from the UK Dietary Cohort Consortium.

BACKGROUND: Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent. METHODS: We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ). RESULTS: Compared with individuals in the lightest category of drinkers (>0-<5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5-<15 g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15-<30 g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30-<45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with >or=45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results. CONCLUSION: We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium.