Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.</p

Impact of obesity on angiogenic and inflammatory markers in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort

Abstract Background: While several studies have demonstrated that obesity increases the risk of pre-eclampsia (PE), the mechanisms have yet to be elucidated. We assessed the association between maternal/paternal obesity and PE and hypothesized that maternal body mass index (BMI) would be associated with an adverse inflammatory and angiogenic profile. High-sensitivity C-reactive protein (hs-CRP) and following serum angiogenic markers were determined: soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Methods: Data on BMI were available from 1450 pregnant women with PE and 1065 without PE. Serum concentrations of hs-CRP and angiogenic markers were available from a subset at first and third trimesters. Results: Prepregnancy BMI was higher in the PE group than in controls (mean ± SD) 25.3 ± 5.2 vs. 24.1 ± 4,4, p < 0.001, adjusted for parity, mother’s age, and smoking status before pregnancy. Increased hs-CRP concentrations were observed in both PE and non-PE women similarly according to BMI category. In women with PE, a higher BMI was associated with lower sFlt-1 and sEng concentrations throughout the pregnancy (p = 0.004, p = 0.008, respectively). There were no differences in PlGF in PE women according to BMI. Conclusions: We confirmed increased pre-pregnancy BMI in women with PE. Enhanced inflammatory state was confirmed in all women with overweight/obesity. Partly paradoxically we observed that PE women with obesity had less disturbed levels of angiogenic markers than normal weight women with PE. This should be taken into account when angiogenic markers are used in PE prediction. Acknowledgements FINNPEC Members: Hannele Laivuori2,7,8,9 (2Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, 7Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland, 8Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland, 9Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland), Seppo Heinonen2 (2Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland), Eero Kajantie10,11,12 (10Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland, 11Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland, 12PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland), Juha Kere13,14,15 (13Department of Biosciences and Nutrition, and Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden, 14Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland, 15Folkhälsan Institute of Genetics, Helsinki, Finland), Katja Kivinen16 (16Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK), Anneli Pouta13,17 (13Department of Biosciences and Nutrition, and Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden, 17Department of Government Services, National Institute for Health and Welfare, Helsinki, Finland

Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study

Epidemiological evidence suggests a role for vitamin D in type 2 diabetes prevention. We investigated the effects of vitamin D3 supplementation on glucose metabolism and inflammation in subjects with prediabetes. A 5-month randomized, double-blind, placebo-controlled intervention with three arms (placebo, 40 μg/d, or 80 μg/d vitamin D3) was carried out among sixty-eight overweight (BMI 25–35) and aging (≥60 years) subjects from Finland, with serum 25-hydroxyvitamin D3 [25(OH)D3] < 75 nmol/L and either impaired fasting glucose or impaired glucose tolerance. Analyses included 66 subjects who completed the trial. Glucose metabolism was evaluated by fasting and 2-hour oral glucose tolerance test-derived indices and glycated hemoglobin. Inflammation was evaluated by high-sensitive C-reactive protein and five cytokines. Although a dose-dependent increase in serum 25(OH)D3 over the supplementation period was observed (P trend < 0.001), there were no other statistically significant differences in changes in the 13 glucose homeostasis indicators between the study groups other than increase in the 120 min glucose concentration (P trend = 0.021) and a decreasing trend both in 30 min plasma insulin (P trend = 0.030) and glycated hemoglobin (P trend = 0.024) concentrations. A borderline statistically significant decreasing trend in interleukin-1 receptor antagonist concentration was observed (P = 0.070). Vitamin D3 supplementation does not improve glucose metabolism in ageing subjects with prediabetes but may have modest anti-inflammatory effects

Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: Educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB)

Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays, and NP assays interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation. Keywords: biotin; hemolysis; interferences; natriuretic peptide; troponin Cardiac troponin I and T (cTnI, cTnT) and the natriuretic peptides (NP; B-type natriuretic peptide, BNP; N Terminal-proBNP; NT-proBNP) are the primary cardiac biomarkers utilized in the diagnosis of myocardial injury and infarction (MI) and heart failure (HF), respectively. As with any clinical laboratory test, there are exogenous and endogenous factors that adversely interfere with the analytical performance of the cTn and NP assays, potentially resulting in inappropriate clinical interpretation of the results if the interferences are not identified. Analytical interferences are particularly concerning when dealing with cardiac biomarker assays, which are utilized to make time sensitive critical clinical decisions. Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7, vitamin H, coenzyme R). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays (Table 1) [1], and NP assays (Table 2) [2] interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation

Fetal microsatellite in the heme oxygenase 1 promoter is associated with severe and early-onset preeclampsia

Abstract Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine–thymine (GTn) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother’s preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GTn repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GTn repeat may increase mother’s risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes

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