Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Eating disorders are relatively common disorders that are often overlooked, although they are associated with high comorbidity and serious health consequences.

Objective: Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC). Methods: The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975)(1976)(1977)(1978)(1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22-27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models. Results: The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r ¼ À0.12) and females (r ¼ À0.18), and between physical activity and BMI in females (r ¼ À0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC. Conclusions: Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.

Objective In 2015, the Academy for Eating Disorders (AED) collaborated with international patient, advocacy, and parent organizations to craft the “Nine Truths About Eating Disorders.” This document has been translated into over 30 languages and has been distributed globally to replace outdated and erroneous stereotypes about eating disorders with factual information. In this paper, we review the state of the science supporting the Nine Truths. Methods The literature supporting each of the Nine Truths was reviewed, summarized, and richly annotated. Results Most of the Nine Truths arise from well-established foundations in the scientific literature. Additional evidence is required to further substantiate some of the assertions in the document. Future investigations are needed in all areas to deepen our understanding of eating disorders, their causes, and their treatments. Conclusions The “Nine Truths About Eating Disorders” is a guiding document to accelerate global dissemination of accurate and evidence-informed information about eating disorders.

Aims/hypothesisMetabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults.MethodsNMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up.ResultsOut of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31–1.33) and triacylglycerol within VLDL particles (OR 1.33–1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years).Conclusions/interpretationMetabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.Electronic supplementary materialThe online version of this article (10.1007/s00125-019-05001-w) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

The definition of anorexia nervosa was revised for the Fifth Edition of the Diagnostic and Statistical Manual (DSM-5). We examined the impact of these changes on the prevalence and prognosis of anorexia nervosa. In a nationwide longitudinal study of Finnish twins born 1975-1979, the women (N = 2825) underwent a 2-stage screening for eating disorders at mean age 24. Fifty-five women fulfilled DSM-IV criteria for lifetime anorexia nervosa. When we recoded the interviews using DSM-5 criteria, we detected 37 new cases. We contrasted new DSM-5 vs. DSM-IV cases to assess their clinical characteristics and prognosis. We also estimated lifetime prevalences and incidences and tested the association of minimum BMI with prognosis. We observed a 60% increase in the lifetime prevalence of anorexia nervosa using the new diagnostic boundaries, from 2.2% to 3.6%. The new cases had a later age of onset (18.8 y vs. 16.5, p = 0.002), higher minimum BMI (16.9 vs. 15.5 kg/m(2), p = 0.0004), a shorter duration of illness (one year vs. three years, p = 0.002), and a higher 5-year probability or recovery (81% vs. 67%, p = 0.002). Minimum BMI was not associated with prognosis. It therefore appears that the substantial increase in prevalence of anorexia nervosa is offset by a more benign course of illness in new cases. Increased diagnostic heterogeneity underscores the need for reliable indicators of disease severity. Our findings indicate that BMI may not be an ideal severity marker, but should be complemented by prognostically informative criteria. Future studies should focus on identifying such factors in prospective settings.

Objective: We aimed to assess the lifetime prevalence, 10-year incidence, and peak periods of onset for eating disorders as defined by the Fifth Diagnostic and Statistical Manual of Mental Disorders (DSM-5) among adolescents and young adults born in the 1980s in Finland.Method: Virtually all Finnish twins born in 1983-1987 (n = 5,600) were followed prospectively from the age of 12 years. A subsample of participants (n = 1,347) was interviewed using a semi-structured diagnostic interview in their early twenties.Results: The prevalence of lifetime DSM-5 eating disorders was 17.9% for females and 2.4% for males (pooled across genders, 10.5%). The estimated lifetime prevalences for females and males, respectively, were 6.2 and 0.3% for anorexia nervosa (AN), 2.4 and 0.16% for bulimia nervosa (BN), 0.6 and 0.3% for binge-eating disorder (BED), 4.5 and 0.16% for other specified feeding or eating disorder (OSFED), and 4.5 and 1.6% for unspecified feeding or eating disorder (UFED). Among females, the prevalence of OSFED subcategories was as follows: atypical AN 2.1%, purging disorder 1.3%, BED of low frequency/limited duration 0.7%, and BN of low frequency/ limited duration 0.4%. The 10-year incidence rate of eating disorders was 1,700 per 100,000 person-years among females (peak age of onset 16-19 years) and 220 per 100,000 person-years among males.Discussion: Eating disorders are a common public health concern among youth and young adults, affecting one in six females and one in 40 males. Adequate screening efforts, prevention, and interventions are urgently needed.

Objective: Advances in metabolomics now allow high-throughput biomarker profiling of large population studies. We aimed to identify circulating metabolic biomarkers predictive of type 2 diabetes in young adults.Methods: Nuclear magnetic resonance metabolomics was used to quantify 229 metabolic measures in 11,896 individuals from four Finnish cohorts (mean age 33 years, range 24-45). Associations between baseline metabolites and risk of type 2 diabetes onset during 8-15 years of follow-up (392 incident cases) were assessed by logistic regression adjusted for sex, age, body mass index, and fasting glucose.Results: Out of 229 metabolic measures, 113 were associated with incident diabetes in metaanalysis of the four cohorts (P<0.0009; odds ratios per 1-SD: 0.59-1.50). Among the strongest predictors of diabetes risk were branched-chained and aromatic amino acids (odds ratios 1.31-1.33), triglyceride fractions within the largest very-low-density lipoprotein particles (VLDL; odds ratios 1.33-1.50)), as well as linoleic omega-6 fatty acids (odds ratio 0.75) and free cholesterol in large high-density lipoprotein particles (HDL; odds ratio 0.59). A biomarker score comprised of phenylalanine, free cholesterol in large HDL, and the ratio of cholesteryl esters to total lipids in large VLDL was predictive of the risk for future diabetes in an independent validation cohort (odds ratio 10.1 [95% confidence intervals 4.2-24.1] comparing individuals in upper vs lower fifth of biomarker score). Adjustment for routine lipids and insulin attenuated the odds ratio to 5.8 [2.2-15.1]. Conclusions:Metabolic aberrations across multiple molecular pathways are predictive of the longterm risk of type 2 diabetes in young adults. Comprehensive metabolic profiling may potentially help targeting preventive interventions for young asymptomatic individuals at increased risk for type 2 diabetes.