Association of childhood bullying victimisation with suicide deaths: findings from a 50-year nationwide cohort study.

BACKGROUND: Bullying victimisation has been associated with increased risk of suicide ideation and attempt throughout the lifespan, but no study has yet examined whether it translates to a greater risk of death by suicide. We aimed to determine the association of bullying victimisation with suicide mortality. METHODS: Participants were drawn from the 1958 British birth cohort, a prospective follow-up of all births in 1 week in Britain in 1958. We conducted logistic regressions on 14 946 participants whose mothers reported bullying victimisation at 7 and 11 years with linked information on suicide deaths through the National Health Service Central Register. RESULTS: Fifty-five participants (48 males) had died by suicide between the age 18 and 52 years. Bullying victimisation was associated with suicide mortality; a one standard deviation increases in bullying victimisation linked to an increased odds for suicide mortality [odds ratio (OR) 1.29; 1.02-1.64] during adulthood. The OR attenuated by 11% after adjustment for individual (e.g. behavioural and emotional problems) and familial characteristics (e.g. adverse childhood experiences, 1.18; 0.92-1.51). Analysis of bullying victimisation frequency categories yields similar results: compared with individuals who had not been bullied, those who had been frequently bullied had an increased odds for suicide mortality (OR 1.89; 0.99-3.62). CONCLUSION: Our study suggests that individuals who have been frequently bullied have a small increased risk of dying by suicide, when no other risk factors is considered. Suicide prevention might start in childhood, with bullying included in a range of inter-correlated vulnerabilities encompassing behavioural and emotional difficulties and adverse experiences within the family.

Estimating the influence of body mass index (BMI) on mortality using offspring BMI as an instrumental variable.

OBJECTIVE: High body mass index (BMI) is an important predictor of mortality but estimating underlying causality is hampered by confounding and pre-existing disease. Here, we use information from the offspring to approximate parental BMIs, with an aim to avoid biased estimation of mortality risk caused by reverse causality. METHODS: The analyses were based on information on 9674 offspring-mother and 9096 offspring-father pairs obtained from the 1958 British birth cohort. Parental BMI-mortality associations were analysed using conventional methods and using offspring BMI as a proxy, or instrument, for their parents' BMI. RESULTS: In the conventional analysis, associations between parental BMI and all-cause mortality were U-shaped (Pcurvature < 0.001), while offspring BMI had linear associations with parental mortality (Ptrend < 0.001, Pcurvature > 0.46). Curvature was particularly pronounced for mortality from respiratory diseases and from lung cancer. Instrumental variable analyses suggested a positive association between BMI and mortality from all causes [mothers: HR per SD of BMI 1.43 (95% CI 1.21-1.69), fathers: HR 1.17 (1.00-1.36)] and from coronary heart disease [mothers: HR 1.65 (1.15-2.36), fathers: HR 1.51 (1.17-1.97)]. These were larger than HR from the equivalent conventional analyses, despite some attenuation by adjustment for social indicators and smoking. CONCLUSIONS: Analyses using offspring BMI as a proxy for parental BMI suggest that the apparent adverse consequences of low BMI are considerably overestimated and adverse consequences of overweight are underestimated in conventional epidemiological studies.

Childhood cognitive skill trajectories and suicide by mid-adulthood: an investigation of the 1958 British Birth Cohort.

BACKGROUND: Poor cognitive abilities and low intellectual quotient (IQ) are associated with an increased risk of suicide attempts and suicide mortality. However, knowledge of how this association develops across the life-course is limited. Our study aims to establish whether individuals who died by suicide by mid-adulthood are distinguishable by their child-to-adolescence cognitive trajectories. METHODS: Participants were from the 1958 British Birth Cohort and were assessed for academic performance at ages 7, 11, and 16 and intelligence at 11 years. Suicides occurring by September 2012 were identified from linked national death certificates. We compared mean mathematics and reading abilities and rate of change across 7-16 years for individuals who died by suicide v. those still alive, with and without adjustment for potential early-life confounding factors. Analyses were based on 14 505 participants. RESULTS: Fifty-five participants (48 males) had died by suicide by age 54 years. While males who died by suicide did not differ from participants still alive in reading scores at age 7 [effect size (g) = -0.04, p = 0.759], their reading scores had a less steep improvement up to age 16 compared to other participants. Adjustments for early-life confounding factors explained these differences. A similar pattern was observed for mathematics scores. There was no difference between individuals who died by suicide v. participants still alive on intelligence at 11 years. CONCLUSIONS: While no differences in tests of academic performance and IQ were observed, individuals who died by suicide had a less steep improvement in reading abilities over time compared to same-age peers.

National Patient Safety Consortium: Learning from Large-Scale Collaboration.

From 2014 to 2018, the Canadian Patient Safety Institute brought together key partners and established the National Patient Safety Consortium to drive a shared action plan for safer healthcare. With ongoing consensus development on key priorities, an unprecedented level of collaboration and shared leadership with diverse stakeholders and patients and families as full partners, the Consortium and its Integrated Patient Safety Action Plan built a culture of engagement and improvement across Canada.

Understanding associations of early-life adversities with mid-life inflammatory profiles: Evidence from the UK and USA.

OBJECTIVES: In two cohorts, we aimed to establish associations between early-life adversities and adult inflammation, and whether adult (a) adiposity or (b) socioeconomic disadvantage are key intermediaries. METHODS: In both cohorts (N = 7661, 1958 British birth cohort; N = 1255, MIDUS), information was used on adult inflammatory markers (C-reactive protein (CRP), fibrinogen and (MIDUS only) interleukin-6 (IL-6)), adiposity and socioeconomic disadvantage, and early-life adversities (neglect, emotional neglect, physical, psychological, sexual abuse and childhood disadvantage). RESULTS: Early-life adversities varied from 1.6% (sexual abuse, 1958 cohort) to 14.3% (socioeconomic disadvantage, MIDUS). Across the two cohorts, associations were consistent for physical abuse, e.g. 16.3%(3.01,29.7) and 17.0%(-16.4,50.3) higher CRP in the 1958 cohort and MIDUS respectively. Associations attenuated after accounting for adult adiposity, e.g. physical abuse (1958 cohort) and sexual abuse (MIDUS, non-white participants) associations were abolished. Some associations attenuated after adjustment for adult socioeconomic disadvantage; e.g. 1958 cohort neglect-CRP associations reduced from 23.2%(13.7,32.6) to 17.7%(8.18,27.2). Across the cohorts, no associations were found for psychological abuse or emotional neglect; associations for childhood socioeconomic disadvantage were inconsistent. CONCLUSIONS: Specific early-life adversities are associated with adult inflammation; adiposity is a likely intermediary factor. Weight reduction and obesity prevention may offset pro-inflammatory related adult disease among those who experienced early-life adversities.

Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.

BACKGROUND: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. METHODS: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. RESULTS: Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m2; OR for CHD, 1.36; 95% CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%-77% per 1 SD). CONCLUSIONS: Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.

Change in health and social factors in mid-adulthood and corresponding changes in leisure-time physical inactivity in a prospective cohort.

BACKGROUND: To identify whether changes in adult health and social factors are associated with simultaneous changes in inactivity. METHODS: Health, social factors and leisure-time inactivity (activity frequency < 1/week) were self-reported at 33y and 50y in the 1958 British birth cohort (N = 12,271). Baseline (33y) health and social factors and also patterns of change in factors 33y-to-50y were related to inactivity 33y-to-50y (never inactive, persistently inactive, deteriorating to inactivity, or improving from inactivity) using multinomial logistic regression. RESULTS: Approximately 31% were inactive at 33y and 50y; 35% changed status 33y-to-50y (17% deteriorating to inactivity, 18% improving from inactivity). Baseline poor health and obesity were associated with subsequent (33y-to-50y) inactivity; e.g. for poor health, relative risk ratios (RRRs) for deteriorating to inactivity (vs never inactive) and improving from inactivity (vs persistently inactive) were 1.38(1.16,1.64) and 0.77(0.63,0.94) respectively. Adverse changes in health and weight were associated with simultaneous adverse changes in inactivity; e.g. worsening health (vs always good/excellent health) was associated with higher risk of deteriorating to inactivity (RRR:2.20(1.85,2.62)) and lower risk of improving from inactivity (RRR:0.61(0.49,0.77)). However, improving health and weight loss were not associated with improving from inactivity. Worsening self-efficacy 33y-to-50y was associated with lower risk of improving from inactivity; there was no association between improving self-efficacy and inactivity change. Downward social mobility was not associated with deteriorating to or improving from inactivity. Changes in depression symptom level, marriage/co-habitation or parenthood 33y-to-50y were not associated with inactivity changes. No associations were observed for employment. CONCLUSIONS: Associated changes in mid-life health factors with deleterious inactivity changes, highlight the importance of maintaining health, weight and self-efficacy across adulthood to deter inactivity.

Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty.

Little is known about genes regulating male puberty. Further, while many identified pubertal timing variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9 × 10(-9)), a menarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6 × 10(-5)) and short adult stature (p = 7.5 × 10(-6)) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies.

A systematic review on the clustering and co-occurrence of multiple risk behaviours.

BACKGROUND: Risk behaviours, such as smoking and physical inactivity account for up to two-thirds of all cardiovascular deaths, and are associated with substantial increased mortality in many conditions including cancer and diabetes. As risk behaviours are thought to co-occur in individuals we conducted a systematic review of studies addressing clustering or co-occurrence of risk behaviours and their predictors. As the main aim of the review was to inform public health policy in England we limited inclusion to studies conducted in the UK. METHODS: Key databases were searched from 1990 to 2016. We included UK based cross-sectional and longitudinal studies that investigated risk behaviours such as smoking, physical inactivity, unhealthy diet. High heterogeneity precluded meta-analyses. RESULTS: Thirty-seven studies were included in the review (32 cross-sectional and five longitudinal). Most studies investigated unhealthy diet, physical inactivity, alcohol misuse, and smoking. In general adult populations, there was relatively strong evidence of clustering between alcohol misuse and smoking; and unhealthy diet and smoking. For young adults, there was evidence of clustering between sexual risk behaviour and smoking, sexual risk behaviour and illicit drug use, and sexual risk behaviour and alcohol misuse. The strongest associations with co-occurrence and clustering of multiple risk behaviours were occupation (up to 4-fold increased odds in lower SES groups) and education (up to 5-fold increased odds in those with no qualifications). CONCLUSIONS: Among general adult populations, alcohol misuse and smoking was the most commonly identified risk behaviour cluster. Among young adults, there was consistent evidence of clustering found between sexual risk behaviour and substance misuse. Socio-economic status was the strongest predictor of engaging in multiple risk behaviours. This suggests the potential for interventions targeting multiple risk behaviours either sequentially or concurrently particularly where there is evidence of clustering. In addition, there is potential for intervening at the social or environmental level due to the strong association with socio-economic status.

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

Early-life predictors of leisure-time physical inactivity in midadulthood: findings from a prospective British birth cohort.

Much adult physical inactivity research ignores early-life factors from which later influences may originate. In the 1958 British birth cohort (followed from 1958 to 2008), leisure-time inactivity, defined as activity frequency of less than once a week, was assessed at ages 33, 42, and 50 years (n = 12,776). Early-life factors (at ages 0-16 years) were categorized into 3 domains (i.e., physical, social, and behavioral). We assessed associations of adult inactivity 1) with factors within domains, 2) with the 3 domains combined, and 3) allowing for adult factors. At each age, approximately 32% of subjects were inactive. When domains were combined, factors associated with inactivity (e.g., at age 50 years) were prepubertal stature (5% lower odds per 1-standard deviation higher height), hand control/coordination problems (14% higher odds per 1-point increase on a 4-point scale), cognition (10% lower odds per 1-standard deviation greater ability), parental divorce (21% higher odds), institutional care (29% higher odds), parental social class at child's birth (9% higher odds per 1-point reduction on a 4-point scale), minimal parental education (13% higher odds), household amenities (2% higher odds per increase (representing poorer amenities) on a 19-point scale), inactivity (8% higher odds per 1-point reduction in activity on a 4-point scale), low sports aptitude (13% higher odds), and externalizing behaviors (i.e., conduct problems) (5% higher odds per 1-standard deviation higher score). Adjustment for adult covariates weakened associations slightly. Factors from early life were associated with adult leisure-time inactivity, allowing for early identification of groups vulnerable to inactivity.

Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.

Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4 to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.

Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits.

BACKGROUND: Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n = 5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n = 5,316) and Twins UK (up to n = 3,943) to replicate our initial findings from 1958BC. RESULTS: After Bonferroni correction, the joint-likelihood ratio test suggested interactions on serum triglycerides (4 SNP - SNP pairs), LDL cholesterol (2 SNP - SNP pairs) and WHR (1 SNP - SNP pair) in the 1958BC. MDR permutation model testing analysis showed one two-way and one three-way interaction to be statistically significant on serum triglycerides in the 1958BC. In meta-analysis of results from two replication cohorts (NFBC66 and Twins UK, total n = 8,183), none of the interactions remained after correction for multiple testing (P(interaction) >0.17). CONCLUSIONS: Our results did not provide strong evidence for interactions between allelic variations in VDR and RXRG genes on metabolic outcomes; however, further replication studies on large samples are needed to confirm our findings.

25-Hydroxyvitamin D and cognitive performance in mid-life.

Hypovitaminosis D has been linked with poor cognitive function, particularly in older adults, but studies lack a lifespan approach; hence, the effects of reverse causality remain unknown. In the present study, we aimed to assess the relationship between 25-hydroxyvitamin D (25(OH)D) concentrations and subsequent cognitive performance in mid-adulthood and the influence of earlier life factors, including childhood cognitive ability, on this association. Information for the present study was obtained from the members of the 1958 British birth cohort (n 6496). Serum 25(OH)D concentration, indicating vitamin D status, was measured at age 45 years. Verbal memory (immediate and delayed word recall), verbal fluency (animal naming) and speed of processing were tested at age 50 years. Information on childhood cognitive ability, educational attainment, vitamin D-related behaviours and other covariates was collected prospectively from participants throughout their life. Childhood cognitive ability and educational attainment by age 42 years were strongly correlated with cognitive performance at age 50 years and with several vitamin D-related behaviours in mid-adulthood, but not with 25(OH)D concentrations at age 45 years. Participants with both low (<25 nmol/l) and high (≥75 nmol/l) 25(OH)D concentrations at age 45 years performed significantly worse on immediate word recall. The associations attenuated after adjustment for childhood cognitive ability, education, and socio-economic position; however, for the immediate word recall test, there was a non-linear association with 25(OH)D after further adjustment for obesity, menopausal status, smoking, alcohol consumption, physical activity and depressive symptoms at age 45 years (P(curvature)=0·01). The present study demonstrated that 25(OH)D concentrations were non-linearly associated with immediate word recall in mid-life. A clarification of the level of 25(OH)D concentrations that is most beneficial for predicting better cognitive performance in mid-life is required.

Life course body mass index, birthweight and lipid levels in mid-adulthood: a nationwide birth cohort study.

AIMS: Improvement in lipid profiles is an important public health and clinical goal for which a better understanding is needed of biological pathways and influences. Evidence is scant on the role of growth, including trajectories of body mass index (BMI), so we aimed to determine whether particular life stages from birth to adulthood are important for lipid levels in mid-adulthood (45 years). METHODS AND RESULTS: In the 1958 British birth cohort (n = 3927 men; 3897 women), weight and height were recorded at: birth (weight only), 7, 11, 16, 23, 33, and 45 years. Birthweight was inversely associated with triglycerides and in women with total- and non-high-density lipoprotein cholesterol; associations were little affected by adjustment for 7-year BMI. Associations between lipids and BMI strengthened with age, e.g. in women, adult (45-year) triglycerides were elevated by 1.54% (95% confidence interval: 0.87-2.21%) and 3.57% (3.29-3.86%), respectively, per kg/m² higher BMI at 11 and 45 years. Body mass index gain was related to lipids, with strongest associations for the interval between 33 and 45 years, where a kg/m² gain in BMI was associated with ~0.6% higher total cholesterol and ~5.3% higher triglycerides. Associations between 45-year BMI and lipids were stronger for those with lowest than highest BMI at younger ages (P for interaction ≤0.05). A long duration of obesity and obesity in childhood but not thereafter were unrelated to adult lipid levels. CONCLUSIONS: Our findings from a large population-based cohort highlight detrimental consequences of high adult BMI for lipids as most pronounced for those with a lower BMI at earlier life stages.

From developmental origins of adult disease to life course research on adult disease and aging: insights from birth cohort studies.

Maturation of long-running birth cohort studies has fostered a life course approach to adult health, function, and disease and related to conceptual frameworks. Using broad concepts of human development including physical, cognitive, and emotional function, birth cohorts provide insights into the processes across the life course and between generations that link to adult outcomes. We discuss findings on the determinants and health consequences of lifetime trajectories of body size, cognitive and emotional function, and socioeconomic position. Findings from the studies suggest that, for some adult health outcomes, explanations will be incomplete unless exposures and processes from across the life course are taken into account. New birth cohort studies are poised to delineate further the nature and timing of life course relationships in contemporary generations of children.

Childcare and overweight or obesity over 10 years of follow-up.

OBJECTIVE: To investigate the predictive association between preschool childcare arrangements and overweight/obesity in childhood. STUDY DESIGN: Children were enrolled in a prospective birth cohort in Quebec, Canada (n = 1649). Information about childcare obtained via questionnaires to the mothers at ages 1.5, 2.5, 3.5, and 4 years was used to compute a main childcare arrangement exposure variable (center-based/family-based/care by a relative/nanny). Body mass index was derived from measured weights and heights at ages 4, 6, 7, 8, and 10 years and children were classified as overweight/obese versus normal weight. Generalized estimating equations were used to model the effect of main childcare arrangement (center-based/family-based/relative/nanny) (vs parental care) on overweight/obesity adjusting for several potential confounding factors. RESULTS: Compared with parental care, children who attended a center-based childcare (OR: 1.65, 95% CI: 1.13-2.41) or were cared for by a relative (OR: 1.50; 95% CI: 0.95-2.38, although with greater uncertainty) had higher odds of being overweight/obese in childhood (4-10 years). Analyses of number of hours additionally suggested that each increment of 5 hours spent in either center-based or relative childcare increased the odds of overweight/obesity in the first decade of life by 9%. Associations were not explained by a wide range of confounding factors, including socioeconomic position, breastfeeding, maternal employment, and maternal body mass index. CONCLUSION: Overweight/obesity was more frequently observed in children who received non-parental care in center-based settings or care by a relative other than the parent. "Obesogeonic" features of these childcare arrangements should be investigated in future studies.

Genetic variants influencing biomarkers of nutrition are not associated with cognitive capability in middle-aged and older adults.

Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and ß-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled ß on Z-score for carriers vs. noncarriers: -0.05 (95% CI: -0.09, -0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D-raising allele of rs2282679 [pooled ß per T allele: -0.03 (95% CI: -0.05, -0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.

Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration.

AIMS: To evaluate the associations of emergent genome-wide-association study-derived coronary heart disease (CHD)-associated single nucleotide polymorphisms (SNPs) with established and emerging risk factors, and the association of genome-wide-association study-derived lipid-associated SNPs with other risk factors and CHD events. METHODS AND RESULTS: Using two case-control studies, three cross-sectional, and seven prospective studies with up to 25 000 individuals and 5794 CHD events we evaluated associations of 34 genome-wide-association study-identified SNPs with CHD risk and 16 CHD-associated risk factors or biomarkers. The Ch9p21 SNPs rs1333049 (OR 1.17; 95% confidence limits 1.11-1.24) and rs10757274 (OR 1.17; 1.09-1.26), MIA3 rs17465637 (OR 1.10; 1.04-1.15), Ch2q36 rs2943634 (OR 1.08; 1.03-1.14), APC rs383830 (OR 1.10; 1.02, 1.18), MTHFD1L rs6922269 (OR 1.10; 1.03, 1.16), CXCL12 rs501120 (OR 1.12; 1.04, 1.20), and SMAD3 rs17228212 (OR 1.11; 1.05, 1.17) were all associated with CHD risk, but not with the CHD biomarkers and risk factors measured. Among the 20 blood lipid-related SNPs, LPL rs17411031 was associated with a lower risk of CHD (OR 0.91; 0.84-0.97), an increase in Apolipoprotein AI and HDL-cholesterol, and reduced triglycerides. SORT1 rs599839 was associated with CHD risk (OR 1.20; 1.15-1.26) as well as total- and LDL-cholesterol, and apolipoprotein B. ANGPTL3 rs12042319 was associated with CHD risk (OR 1.11; 1.03, 1.19), total- and LDL-cholesterol, triglycerides, and interleukin-6. CONCLUSION: Several SNPs predicting CHD events appear to involve pathways not currently indexed by the established or emerging risk factors; others involved changes in blood lipids including triglycerides or HDL-cholesterol as well as LDL-cholesterol. The overlapping association of SNPs with multiple risk factors and biomarkers supports the existence of shared points of regulation for these phenotypes.

The importance of strategic space.

Does anyone own exclusive space in the journey to create a community-based primary healthcare system? What is the role of public health in this important work? This response to the lead paper explores the unique contribution that public health professionals make in transforming our primary healthcare system, focusing on some of the excellent work that is currently happening in Nova Scotia as examples of how public health and primary healthcare are collaborating and each contributing to this exciting journey. Public health does not need to wait to be invited to the party! It has a responsibility to fulfill the mandate that has been given to it and, in doing so, is contributing greatly to positively impacting on the determinants of health.