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Background The study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI. Methods We studied participants of Helsinki Birth Cohort Study born in 1934–1944 (HBCS1934–1944, n  = 1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n  = 5807, NFBC1986, n  = 6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62 years in HBCS1934–1944, at 46 years in NFBC1966 and at 16 years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex. Results The association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (β = 0.79, 95% CI, 0.33, 1.25, p  < 0.001) in NFBC1966. In NFBC1986 this association was attenuated by PRS BMI ( p  = 0.181), and in HBCS1934–1944 there was no association between high early social disadvantage and increased later life BMI (β 0.22, 95% CI –0.91,1.35, p  = 0.700). In HBCS1934–1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (β − 1.34, [− 2.37,-0.31], p  = 0.011; β − 0.46, [− 0.89,-0.03], p  = 0.038, respectively). Conclusions High social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.

Background This paper discusses how collective intelligence (CI) methods can be implemented to improve government data infrastructures, not only to support understanding and primary use of complex national data but also to increase the dissemination and secondary impact of research based on these data. The case study uses the Northern Ireland Longitudinal Study (NILS), a member of the UK family of census/administrative data longitudinal studies (UKLS). Methods A stakeholder-engaged CI approach was applied to inform the transformation of the NILS Research Support Unit (RSU) infrastructure to support researchers in their use of government data, including collaborative decision-making and better dissemination of research outputs. Results We provide an overview of NILS RSU infrastructure design changes that have been implemented to date, focusing on a website redesign to meet user information requirements and the formation of better working partnerships between data users and providers within the Northern Ireland data landscape. We also discuss the key challenges faced by the design team during this project of transformation. Conclusion Our primary objective to improve government data infrastructure and to increase dissemination and the impact of research based on data was a complex and multifaceted challenge due to the number of stakeholders involved and their often conflicting perspectives. Results from this CI approach have been pivotal in highlighting how NILS RSU can work collaboratively with users to maximize the potential of this data, in terms of forming multidisciplinary networks to ensure the research is utilized in policy and in the literature and providing academic support and resources to attract new researchers.

ObjectivesType 2 diabetes (T2D) and comorbid depression challenges clinical management particularly in individuals with overweight. We aim to explore the shared etiology, via lifecourse adiposity, between T2D and depression.MethodsWe used data from birth until 46years from Northern Finland Birth Cohort 1966 (n = 6,372; 53.8% females). We conducted multivariate analyses on three outcomes: T2D (4.2%), depression (19.2%) and as comorbidity (1.8%). We conducted (i) Path analysis to clarify time-dependent body mass index (BMI) related pathways, including BMI polygenic risk scores (PRS); and (ii) Cox regression models to assess whether reduction of overweight between 7years and 31years influence T2D, depression and/or comorbidity. The models were tested for covariation with sex, education, smoking, physical activity, and diet score.ResultsThe odd ratios (OR) of T2D in individuals with depression was 1.68 [95% confidence interval (CI): 1.34–2.11], and no change in estimate was observed when adjusted for covariates. T2D and comorbidity showed similar patterns of relationships in the path analyses (P < 0.001). The genetic risk for obesity (PRS BMI) did not show direct effect on T2D or comorbidity in adulthood but indirectly through measures of adiposity in early childhood and mid-adulthood in the path analysis (P < 0.001). Having early-onset of overweight at 7years and 31years showed highest risk of T2D (OR 3.8, 95%CI 2.4–6.1) and comorbidity (OR 5.0, 95%CI 2.7–9.5), with mild-to-moderate attenuation with adjustments. Depression showed no significant associations.ConclusionsWe found evidence for overweight since childhood as a risk factor for T2D and co-morbidity between T2D and depression, influenced moderately by lifestyle factors in later life. However, no shared early life adiposity related risk factors were observed between T2D and depression when assessed independently in this Finnish setting.

Abstract Delayed motor developmental milestones have been reported to be associated with schizophrenia in previous studies, but no study has examined the relationship between early motor developmental milestones and schizotypy. We have examined this relationship in a prospective birth cohort.In the Northern Finland Birth Cohort 1966, data on 9 early motor developmental milestones were collected prospectively from visits to child welfare centers, and data on adult schizotypy were collected through a questionnaire (N = 4557–4674). Positive schizotypy was measured by the Perceptual Aberration Scale (PAS), negative schizotypy was measured by Physical Anhedonia Scale (PhAS) and Social Anhedonia Scale (SAS). Three related scales were included: Schizoidia Scale (SCHD), Hypomanic Personality Scale (HPS), and Bipolar II Scale (BIP2). We examined the milestone–schizotypy associations before and after excluding cases of schizophrenia from this population-based sample. Hierarchical regression analyses adjusted for covariates and separately for both genders were performed. In men, each extra month of delay in achievement of touching thumb with index finger, sitting unsupported, standing up, walking with support, or walking unsupported was associated with an increase in PAS, PhAS, or SCHD scores, or decrease in BIP2 score (P < .05). In women, each extra month of delay in achievement of turning from back to tummy was associated with an increase in PhAS and SAS scores (P < .05). Schizotypy is associated with delayed motor developmental milestones in early-life, but there is some heterogeneity with regards to types of milestones and gender. These findings suggest delayed motor development confers risk across the continuum of schizophrenia syndrome.

BackgroundThere are various maternal prenatal biopsychosocial (BPS) predictors of birth weight, making it difficult to quantify their cumulative relationship.MethodsWe studied two birth cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) born in 1985–1986 and the Generation R Study (from the Netherlands) born in 2002–2006. In NFBC1986, we selected variables depicting BPS exposure in association with birth weight and performed factor analysis to derive latent constructs representing the relationship between these variables. In Generation R, the same factors were generated weighted by loadings of NFBC1986. Factor scores from each factor were then allocated into tertiles and added together to calculate a cumulative BPS score. In all cases, we used regression analyses to explore the relationship with birth weight corrected for sex and gestational age and additionally adjusted for other factors.ResultsFactor analysis supported a four-factor structure, labelled closely to represent their characteristics as ‘Factor1-BMI’ (body mass index), ‘Factor2-DBP’ (diastolic blood pressure), ‘Factor3-Socioeconomic-Obstetric-Profile’ and ‘Factor4-Parental-Lifestyle’. In both cohorts, ‘Factor1-BMI’ was positively associated with birth weight, whereas other factors showed negative association. ‘Factor3-Socioeconomic-Obstetric-Profile’ and ‘Factor4-Parental-Lifestyle’ had the greatest effect size, explaining 30% of the variation in birth weight. Associations of the factors with birth weight were largely driven by ‘Factor1-BMI’. Graded decrease in birth weight was observed with increasing cumulative BPS score, jointly evaluating four factors in both cohorts.ConclusionOur study is a proof of concept for maternal prenatal BPS hypothesis, highlighting the components snowball effect on birth weight in two different European birth cohorts.

BackgroundThe prevention of the risk of type 2 diabetes (T2D) is complicated by multidimensional interplays between biological and psychosocial factors acting at the individual level. To address the challenge we took a systematic approach, to explore the bio-psychosocial predictors of blood glucose in mid-age.MethodsBased on the 31-year and 46-year follow-ups (5,078 participants, 43% male) of Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio-psychosocial variables at 31 years to enable a data-driven approach. As selection criteria, the variable must be (i) a component of the metabolic syndrome or an indicator of psychosocial health using WHO guidelines, (ii) easily obtainable in general health check-ups and (iii) associated with fasting blood glucose at 46 years (P < 0.10). Exploratory and confirmatory factor analysis were used to derive latent factors, and stepwise linear regression allowed exploration of relationships between factors and fasting glucose.ResultsOf all 26 variables originally considered, 19 met the selection criteria and were included in an exploratory factor analysis. Two variables were further excluded due to low loading (<0.3). We derived four latent factors, which we named as socioeconomic, metabolic, psychosocial and blood pressure status. The combination of metabolic and psychosocial factors, adjusted for sex, provided best prediction of fasting glucose at 46 years (explaining 10.7% of variation in glucose; P < 0.001). Regarding different bio-psychosocial pathways and relationships, the importance of psychosocial factors in addition to established metabolic risk factors was highlighted.ConclusionsThe present study supports evidence for the bio-psychosocial nature of adult glycemic health and exemplifies an evidence-based approach to model the bio-psychosocial relationships. The factorial model may help further research and public health practice in focusing also on psychosocial aspects in maintaining normoglycaemia in the prevention of cardio-metabolic diseases.

ObjectiveEvidence from randomised controlled trials suggests that vitamin D may reduce multimorbidity, but very few studies have investigated specific determinants of vitamin D2 and D3 (two isoforms of 25-hydroxyvitamin D). The aim of the study was to investigate the determinants of vitamin D2 and D3 and to identify the risk factors associated with hypovitaminosis D.DesignCross-sectional study.SettingNorthern Finland Birth Cohort 1966.Participants2374 male and 2384 female participants with data on serum 25(OH)D2 and 25(OH)D3 concentrations measured at 31 years of age (1997), together with comprehensive measures of daylight, anthropometric, social, lifestyle and contraceptive cofactors.MethodsWe assessed a wide range of potential determinants prior to a nationwide fortification programme introduced in Finland. The determinants of 25(OH)D2, 25(OH)D3 and 25(OH)D concentrations were analysed by linear regression and risk factors for being in lower tertile of 25(OH)D concentration by ordinal logistic regression.ResultsAt the time of sampling, 72% of the participants were vitamin D sufficient (≥50 nmol/L). Low sunlight exposure period (vs high) was associated positively with 25(OH)D2 and negatively with 25(OH)D3 concentrations. Use of oral contraceptives (vs non-users) was associated with an increase of 0.17 nmol/L (95% CI 0.08 to 0.27) and 0.48 nmol/L (95% CI 0.41 to 0.56) in 25(OH)D2 and 25(OH)D3 concentrations. Sex, season, latitude, alcohol consumption and physical activity were the factors most strongly associated with 25(OH)D concentration. Risk factors for low vitamin D status were low sunlight exposure defined by time of sampling, residing in northern latitudes, obesity, higher waist circumference, low physical activity and unhealthy diet.ConclusionsWe demonstrate some differential associations of environmental and lifestyle factors with 25(OH)D2 and 25(OH)D3 raising important questions related to personalised healthcare. Future strategies could implement lifestyle modification and supplementation to improve vitamin D2 and D3 status, accounting for seasonal, lifestyle, metabolic and endocrine status.

Wellbeing is associated with both behavioral phenotypes as well as several key life outcomes, such as health, employment, and coping with stressful events. These phenotypes associated with wellbeing could be potential indicators of differential epigenetic patterns between individuals that differ in their levels of wellbeing. We performed the largest epigenome-wide (EWAS) meta-analysis of wellbeing to date by combining whole blood DNA methylation data (Illumina 450k array) from 13 cohorts from Europe, Australia, and the USA (N = 10,757 participants). After correcting for smoking and BMI, no epigenome-wide significant methylation sites were identified. We tested whether a weighted methylation score (MS) based on leave-one-cohort-out EWAS meta-analysis summary statistics predicted wellbeing in an independent cohort, and whether prediction was significant over and above the polygenic score (PGS) for wellbeing. The MS was associated with wellbeing (variance explained=0.22%, p=0.03) and was no longer significant after adding the polygenic score (PGS; variance explained=0.43%, p=0.0046, MS; variance explained=0.07%, p=0.2842). We further compared DNA methylation levels in 16 pairs of monozygotic twins discordant for wellbeing. These analyses revealed no significant within-pair DNA methylation differences at the top-sites from the meta-analysis or in MS. Our results suggest that larger EWAS meta-analyses with uniform phenotype assessment are required to identify methylation sites associated with wellbeing.

The body of primary sources in the collection-including letters, diaries, journals, interviews, recital programmes, and private recordings-spans the Philadelphia-born contralto's six-decade career as a concert singer and advocate for social justice. After having been denied permission by the Daughters of the American Revolution to perform for an integrated audience in Constitution Hall, Anderson famously performed an open-air concert for 75,000 people on Easter Sunday, 9 April 1939, on the steps of the Lincoln Memorial in Washington, DC. The cochairs wish to thank all of the Working Group members for openly sharing their knowledge and expertise throughout the process of writing the book and Guidelines, MLA and SAA for their generous support, colleagues who commented on the draft in its formative stages, and members of SAA's Technical Subcommittee on DACS, who assiduously read and reread drafts of the Guidelines to help shape them into a standard. Sothebys Auction House recently auctioned off the Hip-Hop classic, 'Beat Bop' to benefit The ARChive of Contemporary Music.

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta analysis of epigenome wide association studies (EWAS) of aggressive behavior (N 15,324 participants). Competing Interest Statement The following authors declare a conflict of interest: Barbara Franke received educational speaking fees from Medice. Andrew M. McIntosh has received research support from Eli Lilly, Janssen and The Sackler Trust and speaker fees from Illumina and Janssen. Christine M. Freitag has received funding by the DFG, BMBF, State of Hessen, and the EU. She receives royalties for books on ASD, ADHD, and MDD.