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

Birth weight and adult income: An examination of mediation through adult height and body mass

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; and (iv) the share of the total effect mediated via height is substantial, of approximately 56%

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

Employment 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

Birth weight, adult weight, and cardiovascular biomarkers: Evidence from the Cardiovascular Young Finns Study

This study quantifies the causal effect of birth weight on cardiovascular biomarkers in adulthood using the Cardiovascular Risk in Young Finns Study (YFS). We apply a multivariable Mendelian randomization (MVMR) method that provides a novel approach to improve inference in causal analysis based on a mediation framework. The results show that birth weight is linked to triglyceride levels (beta = 0.294; 95% CI [-0.591, 0.003]) but not to low-density lipoprotein (LDL) cholesterol levels (beta = 0.007; 95% CI [-0.168, 0.183]). The total effect of birth weight on triglyceride levels is partly offset by a mediation pathway linking birth weight to adult BMI (beta = 0.111; 95% CI [-0.013, 0.234]). The negative total effect is consistent with the fetal programming hypothesis. The positive indirect effect via adult BMI highlights the persistence of body weight throughout a person's life and the adverse effects of high BMI on health. The results are consistent with previous findings that both low birth weight and weight gain increase health risks in adulthood

Economic burden of low physical activity and high sedentary behaviour in Finland

Background Low physical activity and high sedentary behaviour are unquestionably relevant for public health while also increasing direct and indirect costs.Methods The authors examined the direct and indirect costs attributable to low physical activity and high sedentary behaviour in Finland in 2017. Costs related to major non-communicable diseases drawn from Finnish registries covered direct costs (outpatient visits, days of inpatient care, medication and institutional eldercare) and indirect costs (sickness-related absences, disability pensions, unemployment benefits, all-cause mortality and losses of income tax revenue). Prevalences of low physical activity and high sedentary behaviour (>= 8 hours per 16 waking hours) were based on self-reports among adolescents or accelerometer data among adults and the elderly from three Finnish population studies: FINFIT 2017, Health 2011 and the Cardiovascular Risk in Young Finns Study. Cost calculations used adjusted population attributable fractions (PAF) and regression models. Total annual costs were obtained by multiplying PAF by the total costs of the given disease.Results The total costs of low physical activity in Finland in 2017 came to approximately euro3.2 billion, of which direct costs accounted for euro683 million and indirect ones for euro2.5 billion. Costs attributable to high sedentary behaviour totalled roughly euro1.5 billion.Conclusion The findings suggest that low physical activity and high sedentary behaviour levels create substantial societal costs. Therefore, actions intended to increase physical activity and reduce excessive sedentary behaviour throughout life may yield not only better health but also considerable savings to society.</p

Does better education mitigate risky health behavior? A mendelian randomization study

Education and risky health behaviors are strongly negatively correlated. Education may affect health behaviors by enabling healthier choices through higher disposable income, increasing information about the harmful effects of risky health behaviors, or altering time preferences. Alternatively, the observed negative correlation may stem from reverse causality or unobserved confounders. Based on the data from the Cardiovascular Risk in Young Finns Study linked to register-based information on educational attainment and family background, this paper identifies the causal effect of education on risky health behaviors. To examine causal effects, we used a genetic score as an instrument for years of education. We found that individuals with higher education allocated more attention to healthy habits. In terms of health behaviors, highly educated people were less likely to smoke. Some model specifications also indicated that the highly educated consumed more fruit and vegetables, but the results were imprecise in this regard. No causal effect was found between education and abusive drinking. In brief, inference based on genetic instruments showed that higher education leads to better choices in some but not all dimensions of health behaviors.</p

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction : The randomized, double-blind, placebo-controlled OXI pilot trial

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to in-terruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocar-dial infarction. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells

Peer reviewe

Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells

Peer reviewe

Characterising the loss-of-function impact of 5' untranslated region variants in 15,708 individuals

Upstream open reading frames (uORFs) are tissue-specific cis-regulators of protein translation. Isolated reports have shown that variants that create or disrupt uORFs can cause disease. Here, in a systematic genome-wide study using 15,708 whole genome sequences, we show that variants that create new upstream start codons, and variants disrupting stop sites of existing uORFs, are under strong negative selection. This selection signal is significantly stronger for variants arising upstream of genes intolerant to loss-of-function variants. Furthermore, variants creating uORFs that overlap the coding sequence show signals of selection equivalent to coding missense variants. Finally, we identify specific genes where modification of uORFs likely represents an important disease mechanism, and report a novel uORF frameshift variant upstream of NF2 in neurofibromatosis. Our results highlight uORF-perturbing variants as an under-recognised functional class that contribute to penetrant human disease, and demonstrate the power of large-scale population sequencing data in studying non-coding variant classes. Upstream open reading frames (uORFs), located in 5' untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.Peer reviewe