Genetic predisposition to adiposity is associated with increased objectively assessed sedentary time in young children.

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.

Education as a moderator of genetic risk for higher body mass index: prospective cohort study from childhood to adulthood.

OBJECTIVES: The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI. SUBJECTS/METHODS: The study comprised 2441 participants (1319 women, 3-18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood. RESULTS: Mean BMI increased from 22.6 to 26.6 kg/m2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02, P<0.001)). The association between the genetic risk score and BMI was more pronounced among those with lower educational level in adulthood (b=-0.12 (95% CI, -0.23-0.01); P=0.036)). No interaction effect was observed between the genetic risk score and parental education (b=0.05 (95% CI, -0.09-0.18; P=0.51)). Diet and physical activity explained little of the interaction effect between the genetic risk score and adulthood education. CONCLUSIONS: In this prospective study, the association of a risk score of 97 genetic variants with BMI was stronger among those with low compared with high education. This suggests lower education in adulthood accentuates the risk of higher BMI in people at genetic risk.

Association study of arcuate nucleus neuropeptide Y neuron receptor gene variation and serum NPY levels in clozapine treated patients with schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) leads to metabolic consequences and comorbidity, social stigmatization and nonadherence in patients with schizophrenia. Neuropeptide Y (NPY) has an important role in appetite and body weight regulation. Associations between AIWG and serum NPY levels, and genetic polymorphisms (SNPs) associated with its serum levels have been little studied in these patients. SUBJECTS AND METHODS: Associations between serum NPY concentration and other metabolic and inflammatory markers, and 215 SNPs in 21 genes (NPY gene, NPY receptor genes and genes encoding arcuate nucleus NPY neuron receptors) were studied in 180 patients with schizophrenia on clozapine treatment. RESULTS: The serum levels of NPY correlated with levels of resistin (r=0.31, P<0.001) and age (r=0.22, P=0.003). In the general linear univariate model the best-fitting model with explanatory factors age, serum resistin level, serum insulin level, BMI and gender explained 18.0% (P<0.001) of the variance of serum NPY. Genetic risk score (GRSNPY) analysis found twelve significant (P<0.05) serum NPY concentration related SNPs among α7 nicotinic acetylcholine receptor gene CHRNA7, insulin receptor gene INSR, leptin receptor gene LEPR, glucocorticoid receptor (GR) gene NR3C1, and NPY gene. However, after permutation test of gene score the predictive value of GRSNPY remained non-significant (P=0.078). CONCLUSIONS: Serum NPY level does not seem to be a feasible biomarker of AIWG. Serum NPY level alterations are not significantly associated with the candidate gene polymorphisms studied.

Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Can electromyographic arousal be detected visually on the Datex-Ohmeda S/5™ anesthesia monitor?

BACKGROUND: Electroencephalogram (EEG)-based depth of anaesthesia monitoring is susceptible to contaminating electromyographic (EMG) activity. Many authorities have suggested that anaesthesiologists using these monitors should interpret the raw EEG waveform seen on the anaesthesia monitor. METHODS: In 34 patients anaesthetized with propofol using two doses of rocuronium (0.6 and 1.2 mg/kg), we studied whether the EMG arousal can be detected visually on the anaesthesia monitor. The Bispectral Index (BIS) and Entropy biosignals on the monitor were recorded with a video camera, and the one-channel EEG recorded by the Entropy strip was collected on a laptop computer. The recordings and the one-channel EEG were analyzed offline by two experts (anaesthesiologist and neurophysiologist), both with a long experience on anaesthesia-related EEG. RESULTS: EMG arousal existed in 14/34 and 13/33 patients in the BIS and Entropy biosignals, respectively. The anaesthesiologist detected EMG on the monitor in 7/14 patients with BIS (sensitivity 50%) and in 4/13 patients with Entropy (31%). The clinical neurophysiologist detected EMG in 6/14 (43%) patients with BIS and in 5/13 (38%) with Entropy. The specificity of the EMG analyses was 55 and 65% with BIS, and 85 and 90% with Entropy. EMG arousal was detected in BIS biosignal in 10/17 and 4/17 patients with 0.6 and 1.2 mg/kg doses of rocuronium (P = 0.04). CONCLUSIONS: In contrast to many EEG phenomena, EMG activity cannot be accurately detected visually from the raw EEG on the anaesthesia monitor. Further development in the quality of the anaesthesia monitors is warranted.

Elevated BIS and Entropy values after sugammadex or neostigmine: an electroencephalographic or electromyographic phenomenon?

BACKGROUND: Sugammadex is designed to antagonize neuromuscular blockade (NMB) induced by rocuronium or vecuronium. In clinical practice, we have noticed a rise in the numerical values of bispectral index (BIS) and Entropy, two electroencephalogram (EEG) - based depth of anesthesia monitors, during the reversal of the NMB with sugammadex. The aim of this prospective, randomized, double-blind study was to test this impression and to compare the effects of sugammadex and neostigmine on the BIS and Entropy values during the reversal of the NMB. METHODS: Thirty patients undergoing gynecological operations were studied. Patients were anesthetized with target-controlled infusions of propofol and remifentanil, and rocuronium was used to induce NMB. After operation, during light propofol-remifentanil anesthesia, NMB was antagonized with sugammadex or neostigmine. During the following 5 min, the numerical values of BIS, BIS electromyographic (BIS EMG) and Entropy were recorded on a laptop computer, as well as the biosignal recorded by the Entropy strip. The Entropy biosignal was studied off-line both in time and frequency domain to see if NMB reversal causes changes in EEG. RESULTS: In some patients, administration of sugammadex or neostigmine caused a significant rise in the numerical values of BIS, BIS EMG and Entropy. This phenomenon was most likely caused by increased electromyographic (EMG) activity. The administration of sugammadex or neostigmine appeared to have only minimal effect on EEG. CONCLUSION: The EMG contamination of EEG causes BIS and Entropy values to rise during reversal of rocuronium-induced NMB in light propofol-remifentanil anesthesia.

Explaining Entropy responses after a noxious stimulus, with or without neuromuscular blocking agents, by means of the raw electroencephalographic and electromyographic characteristics.

BACKGROUND: Entropy™, an anaesthetic EEG monitoring method, yields two parameters: State Entropy (SE) and Response Entropy (RE). SE reflects the hypnotic level of the patient. RE covers also the EMG-dominant part of the frequency spectrum, reflecting the upper facial EMG response to noxious stimulation. We studied the EEG, EMG, and Entropy values before and after skin incision, and the effect of rocuronium on Entropy and EMG at skin incision during sevoflurane-nitrous oxide (N2O) anaesthesia. METHODS: Thirty-eight patients were anaesthetized with sevoflurane-N2O or sevoflurane-N2O-rocuronium. The biosignal was stored and analysed off-line to detect EEG patterns, EMG, and artifacts. The signal, its power spectrum, SE, RE, and RE-SE values were analysed before and after skin incision. The EEG arousal was classified as ß (increase in over 8 Hz activity and decrease in under 4 Hz activity with a typical ß pattern) or δ (increase in under 4 Hz activity with the characteristic rhythmic δ pattern and a decrease in over 8 Hz activity). RESULTS: The EEG arousal appeared in 17 of 19 and 15 of 19 patients (NS), and the EMG arousal in 0 of 19 and 13 of 19 patients (P<0.01) with and without rocuronium, respectively. Both ß (n=30) and EMG arousals increased SE and RE. The δ arousal (n=2) decreased both SE and RE. A significant increase in RE-SE values was only seen in patients without rocuronium. CONCLUSIONS: During sevoflurane-N2O anaesthesia, both EEG and EMG arousals were seen. ß and δ arousals had opposite effects on the Entropy values. The EMG arousal was abolished by rocuronium at the train of four level 0/4.

Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15-30 years at phase 1 and 30-45 years at phase 4) in 982-1780 participants depending on the hostility measure. Few promising areas from chromosome 14 at 99 cM (top SNPs rs3783337, rs7158754, rs3783332, rs2181102, rs7159195, rs11160570, rs941898, P values <3.9 × 10(-8) with nearest gene Enah/Vasp-like (EVL)) were found suggestively to be related to paranoia and from chromosome 7 at 86 cM (top SNPs rs802047, rs802028, rs802030, rs802026, rs802036, rs802025, rs802024, rs802032, rs802049, rs802051, P values <6.9 × 10(-7) with nearest gene CROT (carnitine O-octanoyltransferase)) to cynicism, respectively. Some shared suggestive genetic influence for both paranoia and cynicism was also found from chromosome 17 at 2.8 cM (SNPs rs12936442, rs894664, rs6502671, rs7216028) and chromosome 22 at 43 cM (SNPs rs7510759, rs7510924, rs7290560), with nearest genes RAP1 GTPase activating protein 2 (RAP1GAP2) and KIAA1644, respectively. These suggestive associations did not replicate across all measurement times, which warrants further study on these SNPs in other populations.

Facial muscle activity, Response Entropy, and State Entropy indices during noxious stimuli in propofol-nitrous oxide or propofol-nitrous oxide-remifentanil anaesthesia without neuromuscular block.

BACKGROUND: Entropy is an anaesthetic EEG monitoring method, calculating two numerical parameters: State Entropy (SE, range 0-91) and Response Entropy (RE, range 0-100). Low Entropy numbers indicate unconsciousness. SE uses the frequency range 0.8-32 Hz, representing predominantly the EEG activity. RE is calculated at 0.8-47 Hz, consisting of both EEG and facial EMG. RE-SE difference (RE-SE) can indicate EMG, reflecting nociception. We studied RE-SE and EMG in patients anaesthetized without neuromuscular blockers. METHODS: Thirty-one women were studied in propofol-nitrous oxide (P) or propofol-nitrous oxide-remifentanil (PR) anaesthesia. Target SE value was 40-60. RE-SE was measured before and after endotracheal intubation, and before and after the commencement of surgery. The spectral content of the signal was analysed off-line. Appearance of EMG on EEG was verified visually. RESULTS: RE, SE, and RE-SE increased during intubation in both groups. Elevated RE was followed by increased SE values in most cases. In these patients, spectral analysis of the signal revealed increased activity starting from low (<20 Hz) frequency area up to the highest measured frequencies. This was associated with appearance of EMG in raw signal. No spectral alterations or EMG were seen in patients with stable Entropy values. CONCLUSIONS: Increased RE is followed by increased SE at nociceptive stimuli in patients not receiving neuromuscular blockers. Owing to their overlapping power spectra, the contribution of EMG and EEG cannot be accurately separated with frequency analysis in the range of 10-40 Hz.