Schizophrenia polygenic risk score and long-term success in the labour market : A cohort study

Publisher Copyright: © 2022 The AuthorsEmployment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related to education and labour market outcomes. We found that a higher PGS was linked to lower educational levels and weaker labour market outcomes as well as a higher likelihood of receiving social income transfers, particularly among men. Assuming that the link is causal, our results indicate that individuals with schizophrenia or schizophrenia-related traits have a weakened ability to fully participate in the labour market, potentially reinforcing social exclusion.Peer reviewe

C-reactive Protein and Temperament: An Instrumental Variable Analysis

BACKGROUND: Temperament is associated with circulating inflammatory biomarkers, such as C-reactive protein (CRP), which has been associated with various health conditions, including depression. This study aims to investigate whether genetic disposition for increased circulating CRP concentration may influence temperament over the life-course. METHODS: Using a longitudinal cohort that began in 1980—the Cardiovascular Risk in Young Finns Study (YFS)—we included 920 participants (59.8% female) aged 3–12 years old at baseline (childhood), and the same participants again at ages 30–39 years old (adulthood) in this study. We used both ordinary least-squares regression (OLS linear regression) and instrumental variable (IV) regression to assess associations between CRP concentration and temperament dimensions (negative emotionality, activity, and sociability). To represent genetically determined risk for increase in circulating CRP concentration, we calculated a weighted genetic risk score (GRS) which reflects risk for increased circulating CRP concentration. RESULTS: In OLS linear regression analyses, we found that increased circulating CRP concentration in childhood was associated with slightly higher scores for sociability in childhood (19% increase, CI ​= ​7–32%) and adulthood (13% increase, CI ​= ​2–27%), and lower activity scores in adulthood (15% decrease, CI ​= ​3–25%). For all IV regressions, there were no apparent associations between GRS and temperament in either childhood or adulthood (all p>0.3). The Durbin-Wu-Hausman test for endogeneity produced p-values (all>0.05) that suggest there is no evidence for disagreement between the OLS and IV estimates. CONCLUSIONS: We found no clear evidence for an association of GRS for elevated CRP with childhood or adulthood emotionality, activity, or sociability, although circulating CRP was associated with some of these traits

Uncovering the complex genetic architecture of human plasma lipidome using machine learning methods

Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30-45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value \u3c 0.01) lipidome-genotype relations. Genotype biclusters in these 93 relations contained 5977 SNPs across 3164 genes. Twenty nine of the 93 relations contained genotype biclusters with more than 50% unique SNPs and participants, thus representing most distinct subgroups. We identified 30 significantly enriched biological processes among the SNPs involved in 21 of these 29 most distinct genotype-lipidome subgroups through which the identified genetic variants can influence and regulate plasma lipid related metabolism and profiles. This study identified 29 distinct genotype-lipidome subgroups in the studied Finnish population that may have distinct disease trajectories and therefore could be useful in precision medicine research

Dynamics of the peripheral membrane protein P2 from human myelin measured by neutron scattering - a comparison between wild-type protein and a hinge mutant

Myelin protein P2 is a fatty acid-binding structural component of the myelin sheath in the peripheral nervous system, and its function is related to its membrane binding capacity. Here, the link between P2 protein dynamics and structure and function was studied using elastic incoherent neutron scattering (EINS). The P38G mutation, at the hinge between the β barrel and the α-helical lid, increased the lipid stacking capacity of human P2 in vitro, and the mutated protein was also functional in cultured cells. The P38G mutation did not change the overall structure of the protein. For a deeper insight into P2 structure-function relationships, information on protein dynamics in the 10 ps to 1 ns time scale was obtained using EINS. Values of mean square displacements mainly from protein H atoms were extracted for wild-type P2 and the P38G mutant and compared. Our results show that at physiological temperatures, the P38G mutant is more dynamic than the wild-type P2 protein, especially on a slow 1-ns time scale. Molecular dynamics simulations confirmed the enhanced dynamics of the mutant variant, especially within the portal region in the presence of bound fatty acid. The increased softness of the hinge mutant of human myelin P2 protein is likely related to an enhanced flexibility of the portal region of this fatty acid-binding protein, as well as to its interactions with the lipid bilayer surface requiring conformational adaptations

The serum copper/zinc ratio in childhood and educational attainment: a population-based study

BACKGROUND: Micronutrients are potentially important determinants of adult outcomes such as educational attainment. Copper and zinc have known effects on several medical conditions and cognitive development. Elevated copper and depressed zinc is a common trace metal imbalance. METHODS: We estimate the correlation between the copper/zinc ratio (Cu/Zn) in childhood (year 1980) and educational attainment in adulthood (year 2010). We use the Young Finns Study (YFS) combined with the Finnish Linked Employer-Employee Data (FLEED). The regression models account for confounders such as other biomarkers and parental observables. RESULTS: We report a sizeable, negative correlation between Cu/Zn and educational attainment as measured by education in years, grades as well as the likelihood of completing university education. For example, a one standard deviation increase in Cu/Zn decreases the probability of university education by ∼4%. CONCLUSIONS: The findings are consistent with a Cu/Zn effect influencing cognitive functioning early in life. Future research should explore more deeply the precise mechanisms by which Cu/Zn affects educational attainment

Does neuregulin-1 play a role in Type A behavior? The cardiovascular risk in young Finns study

BACKGROUND: Neuregulin-1 proteins are related to physiological correlates of Type A in terms of cardiac reactivity. Furthermore, neuregulin-1 gene (NRG1) may play a role in cardiovascular disease such as atherosclerosis and coronary heart disease i.e. the suggested "outcomes" of Type A behavior. Therefore, NRG1 is hypothesized to be associated with Type A behavior. METHODS: The study examined whether Type A behavior pattern is associated with the single nucleotide polymorphism (SNP) SNP8NRG221533 of the NRG1. The subjects were 631 men and women participating in the population-based Cardiovascular Risk in Young Finns study in 1992 and 2001. Type A was self-assessed with the Framingham Type A Scale and reassessed nine years later. RESULTS: Type A was associated with NRG1 genotype. Carriers of genotype CC scored lower on Type A compared to the others. CONCLUSION: Our study has pinpointed a SNP in NRG1 that predicts Type A behavior. As previous evidence suggests an association for NRG1 with beta-adrenergic stimulation, its role underlying Type A is discussed

Does higher education protect against obesity? Evidence using Mendelian randomization

Objectives. The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. Methods. Participants (N = 2011) were from the on- going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m(2)) measurements in 2007 and 2011 and genetic information were linked to comprehensive register based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization and used a genetic score as an instrument for education. The genetic score was based on 74 genetic variants that genome- wide association studies (GWASs) have found to be associated with the years of education. Because the genotypes are randomly assigned at conception, the instrument causes exogenous variation in the years of education and thus enables identification of causal effects. Results. The years of education in 2007 were associated with lower BMI in 2007/2011 (regression coefficient (b) = -0.22; 95% Confidence Intervals [CI] = -0.29,-0.14) according to the linear regression results. The results based on Mendelian randomization suggests that there may be a negative causal effect of education on BMI (b = -0.84; 95% CI = -1.77, 0.09). Conclusion. The findings indicate that education could be a protective factor against obesity in advanced countries. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Oxytocin receptor gene (OXTR) variant rs1042778 moderates the influence of family environment on changes in perceived social support over time

Background: Lack of social support is an established risk factor across health outcomes, making it important to examine its family environmental and genetic determinants. Methods: In a 27-year follow-up of the Young Finns Study (N = 2341), we examined with a latent growth curve model whether genes involved in the oxytocin signaling pathway namely, oxytocin receptor gene (OXTR) variants rs1042778, rs2254298, and rs53576-moderate the effect of early-life social experiences on perceived social support across the life span. Mothers reported the emotional warmth and acceptance towards their children at baseline when the participants were from 3 to 18 years old (1980). Perceived family support and support from friends and peripheral sources were assessed in five follow-ups 18 years apart (1989-2007). Results: Maternal emotional warmth and acceptance predicted the initial level of perceived social support across subscales, while the rate of change in family support was affected by the family environment only if participants carried the T-allele of OXTR rsl 042778. This gene-environment interaction was not found for the rate of change in support from friends and peripheral sources and we also did not find associations between latent growth in perceived social support and OXTR variants rs53576 and rs2254298. Limitations: Selective attrition in perceived social support, maternal emotional warmth and acceptance, gender, and SES. Family environment was assessed by a non-standardized measure. Conclusions: OXTR rs1042778 polymorphism seems to contribute to changes in perceived family support in that way that some individuals (T-allele carriers) 'recover', to some extent, from the effects of early-life social experiences, whereas others (G/G genotype carriers) do not.Peer reviewe