Childhood predictors of adult fatty liver. The Cardiovascular Risk in Young Finns Study

Background & Aims: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. Methods: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18 years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. Results: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio = 1.71, 95% confidence interval = 1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p = 0.002). Conclusions: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. Lay summary: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18 years) risk variables with fatty liver assessed in adulthood at the age of 34-49 years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Peer reviewe

Schistosomiasis among Recreational Users of Upper Nile River, Uganda, 2007

After recreational exposure to river water in Uganda, 12 (17%) of 69 persons had evidence of schistosome infection. Eighteen percent self-medicated with praziquantel prophylaxis immediately after exposure, which was not appropriate. Travelers to schistosomiasis-endemic areas should consult a travel medicine physician

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.Peer reviewe

Both youth and long-term vitamin D status is associated with risk of type 2 diabetes mellitus in adulthood: a cohort study

<p><b>Objectives:</b> To determine whether vitamin D status in childhood and adolescence (herein collectively referred to as youth) and the long-term status from youth to adulthood is associated with risk of developing type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) in adulthood.</p> <p><b>Materials and methods:</b> This was a 31-year follow-up study of 2300 participants aged 3–18 years. Multinomial logistic regression was used to assess the association of both (a) baseline 25-hydroxyvitamin D (25OHD) levels and (b) the mean of baseline and the latest follow-up 25OHD levels (continuous variable and quartiles) with incident T2DM and IFG (cut-off = 5.6 mmol/L) in adult life.</p> <p><b>Results:</b> High serum 25OHD levels in youth and also mean values from youth to adulthood were associated with reduced risk of developing T2DM in adulthood (odds ratio, 95% confidence interval= 0.73, 0.57–0.95 and 0.65, 0.51–0.84, respectively, for each SD increment in 25OHD). Compared to Q1, a dose-dependent negative association was observed across other quartiles of youth 25OHD, while the strongest association was found in the Q3 for the mean 25OHD levels. Neither youth nor the mean 25OHD was associated with IFG.</p> <p><b>Conclusions:</b> High serum 25OHD levels in youth, and from child to adult life, were associated with a reduced risk of developing T2DM in adulthood.Key Messages</p><p>High serum 25OHD levels in youth, and between youth and adulthood, were associated with a lower risk of T2DM in adulthood.</p><p>Each SD (15.2 nmol/L) increment in youth serum 25OHD levels was associated with a 26% reduction in odds for T2DM, which was independent of a number of confounding variables and other risk factors for T2DM. A similar magnitude of association was observed for the long-term 25OHD levels between youth and adulthood.</p><p>These findings suggest a potentially simple and cost-effective strategy for reducing adulthood risk of T2DM starting in an earlier stage of life – improving and maintaining vitamin D status throughout youth and early adulthood.</p><p></p> <p>High serum 25OHD levels in youth, and between youth and adulthood, were associated with a lower risk of T2DM in adulthood.</p> <p>Each SD (15.2 nmol/L) increment in youth serum 25OHD levels was associated with a 26% reduction in odds for T2DM, which was independent of a number of confounding variables and other risk factors for T2DM. A similar magnitude of association was observed for the long-term 25OHD levels between youth and adulthood.</p> <p>These findings suggest a potentially simple and cost-effective strategy for reducing adulthood risk of T2DM starting in an earlier stage of life – improving and maintaining vitamin D status throughout youth and early adulthood.</p

Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.Peer reviewe

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P &lt;5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate&lt;0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD