Genetic and Environmental Contributions to Facial Morphological Variation: A 3D Population-Based Twin Study

IntroductionFacial phenotype is influenced by genes and environment; however, little is known about their relative contributions to normal facial morphology. The aim of this study was to assess the relative genetic and environmental contributions to facial morphological variation using a three-dimensional (3D) population-based approach and the classical twin study design.ResultsHeritability of 13 uPC and 17 sPC reached statistical significance, with h² ranging from 38.8% to 78.5% in the former and 30.5% to 84.8% in the latter group. Also, 1222 distances showed evidence of genetic control. Common environment contributed to one PC in both groups and 53 linear distances (4.3%). Unique environment contributed to 17 uPC and 20 sPC and 1245 distances.ConclusionsGenetic factors can explain more than 70% of the phenotypic facial variation in facial size, nose (width, prominence and height), lips prominence and inter-ocular distance. A few traits have shown potential dominant genetic influence: the prominence and height of the nose, the lower lip prominence in relation to the chin and upper lip philtrum length. Environmental contribution to facial variation seems to be the greatest for the mandibular ramus height and horizontal facial asymmetry.     

Genetic and Environmental Contributions to Phenotypic Components of Metabolic Syndrome: A Population‐based Twin Study

The increasing prevalence of metabolic syndrome (MS) poses a serious public‐health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their intercorrelations: waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TGs), and high‐density lipoprotein–cholesterol (HDL‐C). We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% confidence interval (CI): 0.00–0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL‐C, and FPG. HDL‐C was mainly influenced by common environmental factors (0.62, 95% CI: 0.58–0.62), whereas the other five MS components were largely influenced by unique environmental factors (0.32–0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as intercorrelated traits, and to carefully consider environmental and genetic factors in studying MS etiology.     

Neuroimaging during Trance State: A Contribution to the Study of Dissociation

Despite increasing interest in pathological and non-pathological dissociation, few researchers have focused on the spiritual experiences involving dissociative states such as mediumship, in which an individual (the medium) claims to be in communication with, or under the control of, the mind of a deceased person. Our preliminary study investigated psychography – in which allegedly “the spirit writes through the medium''s hand” – for potential associations with specific alterations in cerebral activity. We examined ten healthy psychographers – five less expert mediums and five with substantial experience, ranging from 15 to 47 years of automatic writing and 2 to 18 psychographies per month – using single photon emission computed tomography to scan activity as subjects were writing, in both dissociative trance and non-trance states. The complexity of the original written content they produced was analyzed for each individual and for the sample as a whole. The experienced psychographers showed lower levels of activity in the left culmen, left hippocampus, left inferior occipital gyrus, left anterior cingulate, right superior temporal gyrus and right precentral gyrus during psychography compared to their normal (non-trance) writing. The average complexity scores for psychographed content were higher than those for control writing, for both the whole sample and for experienced mediums. The fact that subjects produced complex content in a trance dissociative state suggests they were not merely relaxed, and relaxation seems an unlikely explanation for the underactivation of brain areas specifically related to the cognitive processing being carried out. This finding deserves further investigation both in terms of replication and explanatory hypotheses.     

A Pilot Study of Demographic and Dopaminergic Genetic Contributions to Weight Change in Kidney Transplant Recipients

Kidney transplant recipients often experience a significant amount of weight gain in the first year post-transplantation. While demographic factors such as age, race, and sex have been associated with weight gain in this population, these factors do not explain all of the variability seen. A number of studies have suggested that genetics also plays a critical role in weight changes. Recently, alterations in the activity of the neurotransmitter dopamine have been associated with weight change, and gene expression studies in kidney transplant recipients have supported this association. The purpose of this pilot study is to first examine the feasibility and methodology, and then to examine the associations of age, race, sex, and genotype for 13 SNPs and 3 VNTRs in 9 dopaminergic pathway genes (ANKK1, DRD2, DRD3, DRD4, SLC6A3/DAT1, MAOA, MAOB, COMT, CPE) for associations with percent weight change at 12 months post-transplantation. Seventy kidney transplant recipients had demographic and clinical data collected as a part of a larger observational study. DNA was extracted from repository buffy coat samples taken at the time of transplant, and genotyped using Taqman and PCR based methods. Three SNPs were independently associated with percent weight change: ANKK1 rs1800497 (r = -0.28, p = 0.05), SLC6A3/DAT1 rs6347 (p = 0.046), and CPE rs1946816 (p = 0.028). Stepwise regression modelling confirmed the combined associations of age (p = 0.0021), DRD4 VNTR 4/5 genotype (p = 0.0074), and SLC6A3/DAT1 rs6347 CC genotype (p = 0.0009) and TT genotype (p = 0.0004) with percent weight change in a smaller sample (n = 35) of these kidney transplant recipients that had complete genotyping. These associations indicate that there may be a genetic, and an age component to weight changes post transplantation.     

Writing in the Air: Contributions of Finger Movement to Cognitive Processing

The present study investigated the interactions between motor action and cognitive processing with particular reference to kanji-culture individuals. Kanji-culture individuals often move their finger as if they are writing when they are solving cognitive tasks, for example, when they try to recall the spelling of English words. This behavior is called kusho, meaning air-writing in Japanese. However, its functional role is still unknown. To reveal the role of kusho behavior in cognitive processing, we conducted a series of experiments, employing two different cognitive tasks, a construction task and a stroke count task. To distinguish the effects of the kinetic aspects of kusho behavior, we set three hand conditions in the tasks; participants were instructed to use either kusho, unrelated finger movements or do nothing during the response time. To isolate possible visual effects, two visual conditions in which participants saw their hand and the other in which they did not, were introduced. We used the number of correct responses and response time as measures of the task performance. The results showed that kusho behavior has different functional roles in the two types of cognitive tasks. In the construction task, the visual feedback from finger movement facilitated identifying a character, whereas the kinetic feedback or motor commands for the behavior did not help to solve the task. In the stroke count task, by contrast, the kinetic aspects of the finger movements influenced counting performance depending on the type of the finger movement. Regardless of the visual condition, kusho behavior improved task performance and unrelated finger movements degraded it. These results indicated that motor behavior contributes to cognitive processes. We discussed possible mechanisms of the modality dependent contribution. These findings might lead to better understanding of the complex interaction between action and cognition in daily life.     

Genetic Contributions to Body Weight in Mice: Relationship of Exploratory Behavior to Weight

Objective: The A/J and C57BL/6J mouse strains differ markedly in their exploratory behavior and their weight gain on a high‐fat diet. We examined the genetic contributions of exploratory behavior to body weight and tested for shared, pleiotropic loci influencing energy homeostasis. Research Methods and Procedures: Segregating (A×B6)F2 intercross (n = 514) and (B6AF1×A/J)N2 backcross (N = 223) populations were studied, phenotyping for weight and exploratory behaviors. Relationships among traits were analyzed by correlations. Weight traits were dissected with a genome‐wide scan. Results: Modest correlations were found between exploratory behaviors and weight, explaining 2% to 14% of the variance. Quantitative trait loci (QTL) for body weight at 8 weeks (wgt8), 10 weeks (wgt10), and 2‐week weight gain (difference between weeks 8 and 10) on a 6% fat diet were mapped. Two QTL on chromosome 1 (peaks at 66 cM and 100 cM; Bw8q1) affected wgt8 [likelihood of the odds ratio (Lod), 3.0 and 4.4] and wgt10 (Lod, 2.2 and 3.4), respectively. In the backcross, a significant QTL on chromosome 4 (peak at 66 cM; Bw8q2) affected wgt 8 (Lod, 3.3) and wgt10 (Lod, 3.1). For 2‐week weight gain, suggestive QTL were mapped on chromosomes 4 and 6. The chromosome 6 QTL region overlaps a human 7q locus for obesity. A search for between‐strain sequence polymorphisms in the leptin and NPY genes was unrevealing. Discussion: In mice, loci influencing exploratory activity play a modest role in body‐weight regulation. Some forms of obesity may emerge from loci regulating normal body weight.     

Integrating Genetic,Neuropsychological and Neuroimaging Data to Model Early-Onset Obsessive Compulsive Disorder Severity

We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the training set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our understanding of the neurobiological basis of the disorder.     

亲本对后代群体的不均等遗传贡献及其优化控制

由于自然选择和人工选择的共同作用,使不同亲本的基因在后代基因库中所占比例有所不同,即亲本对后代群体的不均等遗传贡献。本文分析表明,不均等遗传贡献通过实现选择差和群体有效含量对遗传进展产生影响,并使传统的预估选择反应公式出现误差。育种的目标首先是找出在遗传上真正优秀的个体,同时还应当使越优秀的个体对后代基因库的遗传贡献越大。但后一方面尚未得到系统的研究。本文针对这一点,提出了以加快群体遗传进展为总目标、充分考虑育种约束条件的优化控制遗传贡献率的方法。对蛋鸡育种实际资料的计算结果表明,在同等群体含量水平下,优化不均等遗传贡献模式下所获得的实现选择差可比实际值提高34.27—216.57%。     

Provocation of Symmetry/Ordering Symptoms in Anorexia nervosa: A Functional Neuroimaging Study

Anorexia nervosa (AN), obsessive–compulsive disorder (OCD), and obsessive–compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of ‘ordering’ symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.     

Dissociable Behavioral,Physiological and Neural Effects of Acute Glucose and Fructose Ingestion: A Pilot Study

Previous research has revealed that glucose and fructose ingestion differentially modulate release of satiation hormones. Recent studies have begun to elucidate brain-gut interactions with neuroimaging approaches such as magnetic resonance imaging (MRI), but the neural mechanism underlying different behavioral and physiological effects of glucose and fructose are unclear. In this paper, we have used resting state functional MRI to explore whether acute glucose and fructose ingestion also induced dissociable effects in the neural system. Using a cross-over, double-blind, placebo-controlled design, we compared resting state functional connectivity (rsFC) strengths within the basal ganglia/limbic network in 12 healthy lean males. Each subject was administered fructose, glucose and placebo on three separate occasions. Subsequent correlation analysis was used to examine relations between rsFC findings and plasma concentrations of satiation hormones and subjective feelings of appetite. Glucose ingestion induced significantly greater elevations in plasma glucose, insulin, GLP-1 and GIP, while feelings of fullness increased and prospective food consumption decreased relative to fructose. Furthermore, glucose increased rsFC of the left caudatus and putamen, precuneus and lingual gyrus more than fructose, whereas within the basal ganglia/limbic network, fructose increased rsFC of the left amygdala, left hippocampus, right parahippocampus, orbitofrontal cortex and precentral gyrus more than glucose. Moreover, compared to fructose, the increased rsFC after glucose positively correlated with the glucose-induced increase in insulin. Our findings suggest that glucose and fructose induce dissociable effects on rsFC within the basal ganglia/limbic network, which are probably mediated by different insulin levels. A larger study would be recommended in order to confirm these findings.     

Effectiveness of a Multimodal Community Intervention Program to Prevent Suicide and Suicide Attempts: A Quasi-Experimental Study

Background

Multilevel and multimodal interventions have been suggested for suicide prevention. However, few studies have reported the outcomes of such interventions for suicidal behaviours.

Methods

We examined the effectiveness of a community-based multimodal intervention for suicide prevention in rural areas with high suicide rates, compared with a parallel prevention-as-usual control group, covering a total of 631,133 persons. The effectiveness was also examined in highly populated areas near metropolitan cities (1,319,972 persons). The intervention started in July 2006, and continued for 3.5 years. The primary outcome was the incidence of composite outcome, consisting of completed suicides and suicide attempts requiring admission to an emergency ward for critical care. We compared the rate ratios (RRs) of the outcomes adjusted by sex, age group, region, period and interaction terms. Analyses were performed on an intention-to-treat basis and stratified by sex and age groups.

Findings

In the rural areas, the overall median adherence of the intervention was significantly higher. The RR of the composite outcome in the intervention group decreased 7% compared with that of the control group. Subgroup analyses demonstrated heterogeneous effects among subpopulations: the RR of the composite outcome in the intervention group was significantly lower in males (RR = 0.77, 95% CI 0.59–0.998, p = 0.0485) and the RR of suicide attempts was significantly lower in males (RR = 0.39, 95% CI 0.22–0.68, p = 0.001) and the elderly (RR = 0.35, 95% CI 0.17–0.71, p = 0.004). The intervention had no effect on the RR of the composite outcome in the highly populated areas.

Interpretation

Our findings suggest that this community-based multimodal intervention for suicide prevention could be implemented in rural areas, but not in highly populated areas. The effectiveness of the intervention was shown for males and for the elderly in rural areas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00737165","term_id":"NCT00737165"}}NCT00737165 UMIN Clinical Trials Registry UMIN000000460     

Genetic and Environmental Contributions to BMI in Adolescent and Young Adult Women

The objective of this study was to determine the genetic and environmental contributions to variation in BMI over time in European‐American (EA) and African‐American (AA) adolescent and young adult women. Self‐reported BMI (kg/m²) data from 2,816 EA (1,306 twin pairs, 56.5% monozygotic (MZ)) and 404 AA (178 twin pairs, 42.7% MZ) women at baseline (T1; median age 15 years) and 3,225 EA (1,511 twin pairs, 55.3% MZ) and 539 AA (252 pairs, 43.3% MZ) women at follow‐up (T2; median age 22 years) from a Midwestern US, population‐based twin registry were used to construct biometrical genetic models. For EA women, the majority of the variance in BMI was attributable to additive genetic effects at both time points (82% for each), with the remaining variance attributable to nonshared environment. Genetic and nonshared environment correlations between adolescent and young adult BMI were 0.87 and 0.23, respectively. Among AA women, nonadditive genetic effects comprised 68% of the variance at T1 and 73% at T2, and were highly correlated (r_D = 0.94). The proportions of variance attributable to nonshared environment at T1 (29%) and T2 (25%) were more modestly correlated (r_E = 0.31). The remaining variance in AA women could be attributed to additive genetic effects. Additive vs. nonadditive genetic effects contribute differentially to BMI in AA vs. EA adolescent and young adult women. Additional research is needed to better characterize the environmental and genetic factors related to BMI in persons of different races to aid understanding of the complex determinants of body weight in individuals.