Pregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood.
Detailed molecular profiles (87 ...metabolic measures and 37 cytokines) were measured for up to 4260 women (24-49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status.
Compared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters.
Pregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.
Abstract
Background
This retrospective study clarified patients´ psychiatric morbidity in IPV-related facial fractures; in particular, their additional psychiatric care. We hypothesized that patients ...in need of additional support can be identified, allowing overall care processes to be improved.
Methods
Patients’ age, sex, anamnestic psychiatric disorders, history of substance abuse, and psychiatric interventions were recorded, as well as the perpetrator, location, time of day, assault mechanism, fracture type, treatment, and associated injuries.
Results
In all, 807 adult patients were included in the study. Of these, 205 patients (25.4%) had anamnestic psychiatric disorders that were associated independently with female sex (OR 1.95, 95% CI 1.12, 3.41;
p
= 0.019) or history of substance abuse (OR 5.82, 95% CI 4.01, 8.46;
p
< 0.001). Patients with anamnestic psychiatric disorder were more likely to be subjected to severe violence, with an increased risk for combination fractures (OR 2.51, 95% CI 1.30, 4.83;
p
= 0.006). Of all patients, 61 (7.6%) received a psychiatric intervention within the first 12 months. The most common reasons for intervention were anxiety/fear and psychotic symptoms, surfacing within one month in 57% of patients. Anamnestic psychiatric disorders (OR 2.00, 95% CI 1.04, 3.82;
p
= 0.036), severe mental illnesses (OR 2.45, 95% CI 1.04, 5.77;
p
= 0.040), and use of an offensive weapon (OR 2.11, 95% CI 1.11, 4.02;
p
= 0.023) were the strongest independent predictors of psychiatric intervention.
Conclusions
Our results emphasize the need for more structured treatment protocols for patients sustaining IPV injury. Special attention is recommended for patients with anamnestic psychiatric disorders, severe mental illnesses, and those assaulted with an offensive weapon.
Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence ...variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.
Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood.
A comprehensive ...molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24-49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception. Metabolomics profiles were reassessed for 869 women after 6 years to uncover the metabolic effects of starting, stopping and persistently using hormonal contraception.
The comprehensive molecular profiling allowed multiple new findings on the metabolic associations with the use of COCPs. They were positively associated with lipoprotein subclasses, including all high-density lipoprotein (HDL) subclasses. The associations with fatty acids and amino acids were strong and variable in direction. COCP use was negatively associated with albumin and positively associated with creatinine and inflammatory markers, including glycoprotein acetyls and several growth factors and interleukins. Our findings also confirmed previous results e.g. for increased circulating triglycerides and HDL cholesterol. Starting COCPs caused similar metabolic changes to those observed cross-sectionally: the changes were maintained in consistent users and normalized in those who stopped using. In contrast, POCs were only weakly associated with metabolic and inflammatory markers. Results were consistent across all cohorts and for different COCP preparations and different types of POC delivery.
Use of COCPs causes widespread metabolic and inflammatory effects. However, persistent use does not appear to accumulate the effects over time and the metabolic perturbations are reversed upon discontinuation. POCs have little effect on systemic metabolism and inflammation.
We present a method for communicating personalized genetic risk information to citizens and their physicians using a secure web portal. We apply the method for 3,177 Finnish individuals in the P5 ...Study where estimates of genetic and absolute risk, based on genetic and clinical risk factors, of future disease are reported to study participants, allowing individuals to participate in managing their own health. Our method facilitates using polygenic risk score as a personalized tool to estimate a person's future disease risk while offering a way for health care professionals to utilize the polygenic risk scores as a preventive tool in patient care.
Cardiovascular disease (CVD) incidence, complications and burden differ markedly between women and men. Although there is variation in the distribution of lifestyle factors between the genders, they ...do not fully explain the differences in CVD incidence and suggest the existence of gender-specific genetic risk factors. We aimed to estimate whether the genetic risk profiles of coronary heart disease (CHD), ischemic stroke and the composite end-point of CVD differ between the genders.
We studied in two Finnish population cohorts, using the case-cohort design the association between common variation in 46 candidate genes and CHD, ischemic stroke, CVD, and CVD-related quantitative risk factors. We analyzed men and women jointly and also conducted genotype-gender interaction analysis. Several allelic variants conferred disease risk for men and women jointly, including rs1801020 in coagulation factor XII (HR = 1.31 (1.08-1.60) for CVD, uncorrected p = 0.006 multiplicative model). Variant rs11673407 in the fucosyltransferase 3 gene was strongly associated with waist/hip ratio (uncorrected p = 0.00005) in joint analysis. In interaction analysis we found statistical evidence of variant-gender interaction conferring risk of CHD and CVD: rs3742264 in the carboxypeptidase B2 gene, p(interaction) = 0.009 for CHD, and rs2774279 in the upstream stimulatory factor 1 gene, p(interaction) = 0.007 for CHD and CVD, showed strong association in women but not in men, while rs2069840 in interleukin 6 gene, p(interaction) = 0.004 for CVD, showed strong association in men but not in women (uncorrected p-values). Also, two variants in the selenoprotein S gene conferred risk for ischemic stroke in women, p(interaction) = 0.003 and 0.007. Importantly, we identified a larger number of gender-specific effects for women than for men.
A false discovery rate analysis suggests that we may expect half of the reported findings for combined gender analysis to be true positives, while at least third of the reported genotype-gender interaction results are true positives. The asymmetry in positive findings between the genders could imply that genetic risk loci for CVD are more readily detectable in women, while for men they are more confounded by environmental/lifestyle risk factors. The possible differences in genetic risk profiles between the genders should be addressed in more detail in genetic studies of CVD, and more focus on female CVD risk is also warranted in genome-wide association studies.
Upstream transcription factor 1 (USF1) is a ubiquitously expressed transcription factor controlling several critical genes in lipid and glucose metabolism. Of some 40 genes regulated by USF1, several ...are involved in the molecular pathogenesis of cardiovascular disease (CVD). Although the USF1 gene has been shown to have a critical role in the etiology of familial combined hyperlipidemia, which predisposes to early CVD, the gene's potential role as a risk factor for CVD events at the population level has not been established. Here we report the results from a prospective genetic-epidemiological study of the association between the USF1 variants, CVD, and mortality in two large Finnish cohorts. Haplotype-tagging single nucleotide polymorphisms exposing all common allelic variants of USF1 were genotyped in a prospective case-cohort design with two distinct cohorts followed up during 1992-2001 and 1997-2003. The total number of follow-up years was 112,435 in 14,140 individuals, of which 2,225 were selected for genotyping based on the case-cohort study strategy. After adjustment for conventional risk factors, we observed an association of USF1 with CVD and mortality among females. In combined analysis of the two cohorts, female carriers of a USF1 risk haplotype had a 2-fold risk of a CVD event (hazard ratio HR 2.02; 95% confidence interval CI 1.16-3.53; p = 0.01) and an increased risk of all-cause mortality (HR 2.52; 95% CI 1.46-4.35; p = 0.0009). A putative protective haplotype of USF1 was also identified. Our study shows how a gene identified in exceptional families proves to be important also at the population level, implying that allelic variants of USF1 significantly influence the prospective risk of CVD and even all-cause mortality in females.
The genetic background of complex diseases is proposed to consist of several low-penetrance risk loci. Addressing this complexity likely requires both large sample size and simultaneous analysis of ...different predisposing variants. We investigated the role of four thrombosis genes: coagulation factor V (F5), intercellular adhesion molecule 1 (ICAM1), protein C (PROC), and thrombomodulin (THBD) in cardiovascular diseases. Single allelic gene variants and their pair-wise combinations were analyzed in two independently sampled population cohorts from Finland. From among 14,140 FINRISK participants (FINRISK-92, n = 5,999 and FINRISK-97, n = 8,141), we selected for genotyping a sample of 2,222, including 528 incident cardiovascular disease (CVD) cases and random subcohorts totaling 786. To cover all known common haplotypes (>10%), 54 single nucleotide polymorphisms (SNPs) were genotyped. Classification-tree analysis identified 11 SNPs that were further analyzed in Cox's proportional hazard model as single variants and pair-wise combinations. Multiple testing was controlled by use of two independent cohorts and with false-discovery rate. Several CVD risk variants were identified: In women, the combination of F5 rs7542281 x THBD rs1042580, together with three single F5 SNPs, was associated with CVD events. Among men, PROC rs1041296, when combined with either ICAM1 rs5030341 or F5 rs2269648, was associated with total mortality. As a single variant, PROC rs1401296, together with the F5 Leiden mutation, was associated with ischemic stroke events. Our strategy to combine the classification-tree analysis with more traditional genetic models was successful in identifying SNPs-acting either in combination or as single variants--predisposing to CVD, and produced consistent results in two independent cohorts. These results suggest that variants in these four thrombosis genes contribute to arterial cardiovascular events at population level.
Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases
. We estimated their added value in clinical risk prediction of five common diseases, using large-scale ...biobank data (FinnGen; n = 135,300) and the FINRISK study with clinical risk factors to test genome-wide PRSs for coronary heart disease, type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer. We evaluated the lifetime risk at different PRS levels, and the impact on disease onset and on prediction together with clinical risk scores. Compared to having an average PRS, having a high PRS contributed 21% to 38% higher lifetime risk, and 4 to 9 years earlier disease onset. PRSs improved model discrimination over age and sex in type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer, and over clinical risk in type 2 diabetes, breast cancer and prostate cancer. In all diseases, PRSs improved reclassification over clinical thresholds, with the largest net reclassification improvements for early-onset coronary heart disease, atrial fibrillation and prostate cancer. This study provides evidence for the additional value of PRSs in clinical disease prediction. The practical applications of polygenic risk information for stratified screening or for guiding lifestyle and medical interventions in the clinical setting remain to be defined in further studies.
The study aimed to clarify psychiatric morbidity in patients who underwent orthognathic surgery (OS) pre- and postoperatively.
Patients ≥18 years undergoing OS were included in this retrospective ...study. The outcome variable was the incidence of new mild, moderate, or severe psychiatric morbidity or exacerbation of preexisting psychiatric morbidity postoperatively. Surgery and patient-related background variables for outcome were analyzed (SPSS for Macintosh, version 27; IBM SPSS, Inc., Armonk, NY, USA).
Of 182 patients, 44 (24%) had preceding psychiatric morbidity. It was associated significantly with history of alcohol abuse (P < .001) and smoking (P = .046) and was more common in older patients (P = .042). During the postoperative phase, new psychiatric morbidity or exacerbation of a preexisting psychiatric condition was found in 12 patients (7%). Preceding psychiatric history (OR 8.88, P = .004) and high-dose perioperative dexamethasone (OR 9.81, P = .036) were independent predictors for postoperative psychiatric morbidity. No other evaluated variables were associated with outcome.
Psychiatric conditions are common among OS patients. Treatment planning should consider the patient's mental health to minimize the risk of exacerbating psychiatric conditions, and collaboration with psychiatric professionals is recommended. Perioperative high-dose dexamethasone should be used with caution considering possible adverse psychiatric effects.
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