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The objective of this study was to investigate the genetic link between the age at first birth (AFB) and the occurrence of preterm labor and delivery, utilizing Mendelian randomization (MR) data alongside genomewide association analysis (GWAS). We obtained AFB-related GWAS summary data from the European Bioinformatics Institute database and preterm labor and delivery data was sourced from the FinnGen Consortium. The study considered AFB as exposure variables, with the incidence of preterm labor and delivery serving as the outcome variable. Several MR analysis methods, such as inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted mode were utilized. Besides MR-Egger intercepts, Cochrane’s Q test evaluated heterogeneity in the MR data, while MR-PRESSO test checked for horizontal pleiotropy. To assess the association’s sensitivity, A leave-one-out approach was utilized to evaluate the sensitivity of the association. The IVW analysis validated that AFB is an independent risk factor for preterm labor and delivery (p < .001). Horizontal pleiotropy was unlikely to bias causality (p > .05). The likelihood of horizontal pleiotropy affecting causality was low (p > .05), and there was no indication of heterogeneity among the genetic variants (p > .05). Ultimately, a leave-one-out analysis confirmed the stability and reliability of this correlation. Our research indicated that AFB is a protective factor for preterm labor and delivery. Further research is required to clarify the possible mechanisms.
Past studies indicate daily increases in estrogen across the menstrual cycle protect against binge-eating (BE) phenotypes (e.g. emotional eating), whereas increases in progesterone enhance risk. Two previous studies from our laboratory suggest these associations could be due to differential genomic effects of estrogen and progesterone. However, these prior studies were unable to directly model effects of daily changes in hormones on etiologic risk, instead relying on menstrual cycle phase or mean hormone levels. The current study used newly modified twin models to examine, for the first time, the effects of daily changes in estradiol and progesterone on genetic/environmental influences on emotional eating in our archival twin sample assessed across 45 consecutive days.
Methods
Participants included 468 female twins from the Michigan State University Twin Registry. Daily emotional eating was assessed with the Dutch Eating Behavior Questionnaire, and daily saliva samples were assayed for ovarian hormone levels. Modified genotype × environment interaction models examined daily changes in genetic/environmental effects across hormone levels.
Results
Findings revealed differential effects of daily changes in hormones on etiologic risk, with increasing genetic influences across progesterone levels, and increasing shared environmental influences at the highest estradiol levels. Results were consistent across primary analyses examining all study days and sensitivity analyses within menstrual cycle phases.
Conclusions
Findings are significant in being the first to identify changes in etiologic risk for BE symptoms across daily hormone levels and highlighting novel mechanisms (e.g. hormone threshold effects, regulation of conserved genes) that may contribute to the etiology of BE.
We sought to examine the relative importance of surgical lesion complexity versus the presence of genetic/syndromic/extracardiac anomalies (GSAs) in determining survival, morbidity or need for reinterventions following repair for aortic arch hypoplasia.
Methods:
A single-centre, retrospective cohort study of infants undergoing biventricular aortic arch repair via sternotomy from 2010 to 2021 was conducted. Survival analysis was performed using Kaplan–Meier methods, with additional Bayesian survival modelling for subgroups. Composite morbidity comprised respiratory, renal, neurologic, or sepsis-related complications.
Results:
Of 83 included infants, n = 13/83 (15.7%) had complex repairs; 27/83 (32.5%) were GSA+. Operative mortality was significantly higher in GSA+ versus GSA− patients (18.5% vs. 1.8%; p = 0.01), though not for complex versus non-complex repairs. Overall 10-year Kaplan–Meier survival was 86.7%. Bayesian modelling suggested equivalent post-discharge attrition in non-complex/GSA+ and complex/GSA− patients, with the poorest outcomes in complex/GSA+ patients; non-complex/GSA− patients had 100% survival. GSA+ patients exhibited higher composite morbidity (44.4% vs. 7.1% in GSA− p < 0.001), with their mode of death seemingly related to a high incidence of respiratory and neurological morbidity, notably in Dandy–Walker syndrome. The 10-year freedom from arch reinterventions was 87.7%; neither complexity, GSA status, nor post-repair peak arch velocity predicted the need for arch reinterventions.
Conclusions:
Whilst anatomic complexity may have been somewhat neutralised as a risk factor for operative mortality, in contrast to GSA+ status, there is further post-discharge attrition attributable to complexity or GSA+ status, with additive risk effects. Morbidity directly related to certain syndromes underlies some of this risk. Non-anatomic substrates represent a persistent limitation to outcomes of surgical aortic arch repair in infants.
Edited by
David Kingdon, University of Southampton,Paul Rowlands, Derbyshire Healthcare NHS foundation Trust,George Stein, Emeritus of the Princess Royal University Hospital
Eating disorders are complex and serious illnesses that can result in physical and psychiatric comorbidities, medical emergencies and progressive health consequences. Although general psychiatrists may be called upon to assist in emergencies or differential diagnoses, training in this area has been limited. The author attempts to fill the gap by providing a summary of the most recent advances in the field of eating disorders in this chapter to help orient trainees and general psychiatrists. This chapter provides an overview of the most recent changes to the DSM-5 and ICD-11 diagnostic categories for eating disorders, as well as their epidemiology, aetiology and treatment, including the management of complications and life-threatening medical emergencies.
The chapter summarises recent advances in the genetic and neurobiological understanding of eating disorders, as well as emerging new research. These scientific advances have the potential to contribute to the development of new, more-effective eating disorder treatments in the future.
We took a multilevel developmental contextual approach and characterized trajectories of alcohol misuse from adolescence through early midlife, examined genetic and environmental contributions to individual differences in those trajectories, and identified adolescent and young adult factors associated with change in alcohol misuse. Data were from two longitudinal population-based studies. FinnTwin16 is a study of Finnish twins assessed at 16, 17, 18, 25, and 35 years (N = 5659; 52% female; 32% monozygotic). The National Longitudinal Study of Adolescent to Adult Health (Add Health) is a study of adolescents from the United States, who were assessed at five time points from 1994 to 2018 (N = 18026; 50% female; 64% White, 21% Black, 4% Native American, 7% Asian, 9% Other race/ethnicity). Alcohol misuse was measured as frequency of intoxication in FinnTwin16 and frequency of binge drinking in Add Health. In both samples, trajectories of alcohol misuse were best described by a quadratic growth curve: Alcohol misuse increased across adolescence, peaked in young adulthood, and declined into early midlife. Individual differences in these trajectories were primarily explained by environmental factors. Several adolescent and young adult correlates were related to the course of alcohol misuse, including other substance use, physical and mental health, and parenthood.
We explore ethical premises and practical implications of using genetic testing to predict suicide risk. Twin studies indicate heritable components of suicide risk, and associated heritability of mental disorders. Currently, genetics research has abandoned seeking single gene Mendelian determinants, in favour of complex probabilistic epigenetic models. Genome-Wide Association Studies (GWAS) may identify thousands of single nucleotide polymorphisms (SNPs), each contributing very little to the variance in behavioural phenotypes. Since suicide is a behaviour rather than a phenotype, with many different causal aetiologies, it is impossible to predict the behaviours of individuals. We analyse practical and ethical issues that would arise if future research were to identify genetic information that accurately predicts suicide. We examine analytical validity, clinical validity, clinical utility and ethical, legal and social implications. Low sensitivity and specificity for predicting suicide diminish potential advantages and exacerbate risks. We discuss risks of unregulated direct-to-consumer genetic testing services. If someday genetic testing can accurately identify suicide risk in individuals, its use would be contraindicated if we cannot provide effective preventive interventions and mitigate negative impacts of informing people of their suicide risk.
Development and Psychopathology has been a premier resource for understanding stressful childhood experiences and the intergenerational continuity of psychopathology. Building on that tradition, we examined the unique and joint influences of maternal stress on children’s effortful control (age 7) and externalizing behavior (age 11) as transmitted via genetics, the prenatal environment, and the postnatal environment. The sample included N = 561 adopted children and their biological and adoptive parents. Path models identified a direct effect of biological mother life stress on children’s effortful control (β = −.08) and an indirect effect of her life stress on child externalizing behavior via effortful control (β = .52), but no main or indirect effects of biological parent psychopathology, prenatal stress, or adoptive mother adverse childhood experiences (ACES). Adoptive mother ACES amplified the association between biological mother life stress and child effortful control (β = −.08), externalizing behavior (β = 1.41), and the indirect effect via effortful control, strengthening associations when adoptive mothers reported average or high ACES during their own childhoods. Results suggest that novel study designs are needed to enhance the understanding of how life stress gets “under the skin” to affect psychopathology in the offspring of adults who have experienced stress.
Genetic disorders commonly present or show severe manifestations early in life and in reproductive-age women. The impacts of such disorders in pregnancy are complex, often involving both mother and fetus. This chapter provides an overview of key concepts in genetics, focusing on the patterns of inheritance of monogenic disorders. The features and management of several common disorders are discussed, including alpha-1 antitrypsin deficiency, autosomal dominant polycystic kidney disease, Charcot Marie Tooth disease, Ehlers Danlos syndrome, Loeys-Dietz syndrome, glucose-6-phosphate dehydrogenase deficiency, Down syndrome, Turner syndrome, and mitochondrial disorders with a focus on management considerations, relevant for the practice of the obstetric anesthesiologist.
In South America, the knowledge of trematode diversity parasitizing freshwater fishes is still scarce, as less than 5% of the freshwater fish fauna has been examined for parasites. A similar situation applies to studies on digenean life cycles, which have become increasingly rare. Among the digenean families parasitizing freshwater fishes in the region, Haploporidae is considered the richest in species diversity. However, information about the developmental stages of haploporid life cycles remains fragmentary. Particularly, in Argentina, nine cercariae attributed to the family Haploporidae have been described using morphological analysis, and only two life cycles of this family have been completely elucidated. In this study a new type of cercaria, morphologically assigned to the family Haploporidae and collected from the snail Heleobia parchappii (Cochliopidae) in Los Padres shallow lake, Buenos Aires province, was identified using morphological and molecular techniques. The molecular analysis, based on 28S and ITS2 sequences, revealed that the cercariae were 100% identical to adult specimens of Saccocoelioides nanii (Haploporidae) parasitizing the fish Prochilodus lineatus (Prochilodontidae) from Los Talas, Buenos Aires province. Our results not only provide information about the life cycle of S.nanii but also show that a molecular and morphological approach can be extremely useful in identifying the developmental stages of digeneans and elucidating their life cycles.
Opioid use disorder is currently viewed as a chronic disease characterized by specific drug-seeking behaviors and compulsive use patterns. In general, these behaviors are difficult to control, and occur despite harmful consequences to the user, but not every person who is exposed to an opioid becomes addicted. The disease of addiction is complex and multifactorial and, as of this writing, a single factor has not been identified that can either accurately predict or quantify the risk that a given individual will develop opioid use disorder. Like most diseases, there is a combination of factors at play, which can influence the risk for addiction. The more risk factors a person has, the greater the chance that exposure to opioids will lead to addiction. Conversely, the fewer risk factors an individual has, the less likely that exposure will result in opioid use disorder. Specific risk factors discussed in this chapter include biological (genetic predisposition), environmental (exposure during critical points in development) and social factors such as accepted use within certain communities and variable access to medical care for members of different socioeconomic status.
Aging plays a crucial role in the mechanisms of the impacts of genetic and environmental factors on blood pressure and serum lipids. However, to our knowledge, how the influence of genetic and environmental factors on the correlation between blood pressure and serum lipids changes with age remains to be determined. In this study, data from the Chinese National Twin Registry (CNTR) were used. Resting blood pressure, including systolic and diastolic blood pressure (SBP and DBP), and fasting serum lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) were measured in 2378 participants (1189 twin pairs). Univariate and bivariate structural equation models examined the genetic and environmental influences on blood pressure and serum lipids among three age groups. All phenotypes showed moderate to high heritability (0.37–0.59) and moderate unique environmental variance (0.30–0.44). The heritability of all phenotypes showed a decreasing trend with age. Among all phenotypes, SBP and DBP showed a significant monotonic decreasing trend. For phenotype-phenotype pairs, the phenotypic correlation (Rph) of each pair ranged from −0.04 to 0.23, and the additive genetic correlation (Ra) ranged from 0.00 to 0.36. For TC&SBP, TC&DBP, TG&SBP and TGs&DBP, both the Rph and Ra declined with age, and the Ra difference between the young group and the older adult group is statistically significant (p < .05). The unique environmental correlation (Re) of each pair did not follow any pattern with age and remained relatively stable with age. In summary, we observed that the heritability of blood pressure was affected by age. Moreover, blood pressure and serum lipids shared common genetic backgrounds, and age had an impact on the phenotypic correlation and genetic correlations.
Neurodevelopmental disorders is an umbrella term that incorporates a range of conditions characterised by some form of disruption to ‘typical’ brain development. These disorders share aetiological pathways that have genetic, social and environmental risk factors. Neurodevelopmental disorders often have core features in common and they frequently co-occur. Long-term impairment is characteristic, although key features may vary over the life span. This chapter covers key aspects of the aetiology of neurodevelopmental disorders, in particular focusing on those found in forensic settings (such as autism spectrum disorder, intellectual disability, attention deficit and hyperactivity disorder and fetal alcohol spectrum disorder). The impact of genetic, social and environmental risk factors is considered. The chapter considers the aetiology of neurodevelopmental disorders as relevant to forensic settings.
In the UK, broiler chickens are normally slaughtered at about six weeks of age when they weigh approximately 2.2 kg; this contrasts with the growth of an ‘unimproved’ traditional strain of bird such as a White Sussex, which would weigh about 800 g at the same age. Lameness, characterised by abnormal gait, posture and impaired walking ability, can be prevalent in these rapidly growing birds and has been highlighted as a major welfare concern. It is during the later stages of rearing, when the bird is becoming heavy and may be achieving weight gains of over 50 g per day, that lameness begins to have an economic and welfare impact on the flock and to compromise the behaviour of large numbers of birds. A study was carried out to identify potential differences in the expression of genes between groups of lame and normal broiler chickens using subtraction hybridisation. The first group comprised lame birds with measurable gait abnormalities, and the second group comprised sound (not lame) birds. Both populations came from within the same flock. After extraction of mRNA and creation of cDNA, subtractive hybridisation was performed to eliminate genetic sequences common to both populations. The resultant DNA was separated and presented for sequence data analysis and comparison with a large sequence database. Some examples of the subtracted sequences detected are given, and the potential significance of these sequence differences at the individual and group level is discussed.
Some children are more affected by specific family environments than others, as a function of differences in their genetic make-up. However, longitudinal studies of genetic moderation of parenting effects during early childhood have not been conducted. We examined developmental profiles of child behavior problems between 18 months and age 8 in a longitudinal parent–offspring sample of 361 adopted children. In toddlerhood (18 months), observed structured parenting indexed parental guidance in service of task goals. Biological parent psychopathology served as an index of genetic influences on children’s behavior problems. Four profiles of child behavior problems were identified: low stable (11%), average stable (50%), higher stable (29%), and high increasing (11%). A multinominal logistic regression analysis indicated a genetically moderated effect of structured parenting, such that for children whose biological mother had higher psychopathology, the odds of the child being in the low stable group increased as structured parenting increased. Conversely, for children whose biological mother had lower psychopathology, the odds of being in the low stable group was reduced when structured parenting increased. Results suggest that increasing structured parenting is an effective strategy for children at higher genetic risk for psychopathology, but may be detrimental for those at lower genetic risk.
The behavioral issues experienced by individuals with Prader-Willi Syndrome (PWS) can be both surprising and overwhelming to clinicians and caregivers. Despite the distress and dysfunction posed by them, there are very few resources available to address these neuropsychiatric problems. This invaluable guidebook helps to identify and address the spectrum of behavioral issues faced by individuals with PWS. Written by a psychiatrist with unique expertise in the management of patients with this condition, this easy-to-read book explores practical details that will aid any clinician or caregiver. Chapters offer vivid case examples and clear guidance on both the behavioral and pharmacological management of issues such as anxiety, skin-picking, ADHD, disruptive behavior (including non-suicidal self-harm), mood disorders (including depression and bipolar disorder), and psychosis. Neuro-behavioral Manifestations of Prader-Willi Syndrome serves as an essential and practical companion for any caregiver or healthcare professional providing care to people with PWS.
A moderate to high alcohol consumption is associated with a lower risk of cardiovascular disease (CVD) mortality in comparison with low consumption. The mechanisms underlying this association are not clear and have been suggested to be caused by residual confounding. The main objective of this study was to separate the familial and individual risk for CVD mortality and all-cause mortality related to alcohol consumption. This will be done by estimating the risk for CVD mortality and all-cause mortality in twin pairs discordant for alcohol consumption.
Methods
Alcohol consumption was assessed at two time points using self-report questionnaires in the Norwegian Twin Registry. Data on CVD mortality was obtained from the Norwegian Cause of Death Registry. Exposure–outcome associations for all-cause mortality and mortality due to other causes than CVD were estimated for comparison.
Results
Coming from a family with moderate to high alcohol consumption was protective against cardiovascular death (HR = 0.54, 95% CI 0.65–0.83). Moderate and high alcohol consumption levels were associated with a slightly increased risk of CVD mortality at the individual level (HR = 1.33, 95% CI 1.02–1.73). There was no association between alcohol consumption and all-cause mortality both at the familial nor at the individual level.
Conclusions
The protective association of moderate to high alcohol consumption with a lower risk of CVD mortality was accounted for by familial factors in this study of twins. Early life genetic and environmental familial factors may mask an absence of health effect of moderate to high alcohol consumption on cardiovascular mortality.
Previous research has shown that self-reports of the amount of social support are heritable. Using the Kessler perceived social support (KPSS) measure, we explored sex differences in the genetic and environmental contributions to individual differences. We did this separately for subscales that captured the perceived support from different members of the network (spouse, twin, children, parents, relatives, friends and confidant). Our sample comprised 7059 male, female and opposite-sex twin pairs aged 18−95 years from the Australian Twin Registry. We found tentative support for different genetic mechanisms in males and females for support from friends and the average KPSS score of all subscales, but otherwise, there are no sex differences. For each subscale alone, the additive genetic (A) and unique environment (E) effects were significant. By contrast, the covariation among the subscales was explained — in roughly equal parts — by A, E and the common environment, with effects of different support constellations plausibly accounting for the latter. A single genetic and common environment factor accounted for between half and three-quarters of the variance across the subscales in both males and females, suggesting little heterogeneity in the genetic and environmental etiology of the different support sources.
Anguillicoloides crassus is an invasive nematode parasite of the critically endangered European eel, Anguilla anguilla, and possibly one of the primary drivers of eel population collapse, impacting many features of eel physiology and life history. Early detection of the parasite is vital to limit the spread of A. crassus, to assess its potential impact on spawning biomass. However accurate diagnosis of infection could only be achieved via necropsy. To support eel fisheries management we developed a rapid, non-lethal, minimally invasive and in situ DNA-based method to infer the presence of the parasite in the swim bladder. Screening of 131 wild eels was undertaken between 2017 and 2019 in Ireland and UK to validate the procedure. DNA extractions and PCR were conducted using both a Qiagen Stool kit and in situ using Whatman qualitative filter paper No1 and a miniPCR DNA Discovery-System™. Primers were specifically designed to target the cytochrome oxidase mtDNA gene region and in situ extraction and amplification takes approximately 3 h for up to 16 individuals. Our in-situ diagnostic procedure demonstrated positive predictive values at 96% and negative predictive values at 87% by comparison to necropsy data. Our method could be a valuable tool in the hands of fisheries managers to enable infection control and help protect this iconic but critically endangered species.
Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5−36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
Polygenic risk scores (PRSs) capture genetic vulnerability to psychiatric conditions. However, PRSs are often associated with multiple mental health problems in children, complicating their use in research and clinical practice. The current study is the first to systematically test which PRSs associate broadly with all forms of childhood psychopathology, and which PRSs are more specific to one or a handful of forms of psychopathology.
Methods
The sample consisted of 4717 unrelated children (mean age = 9.92, s.d. = 0.62; 47.1% female; all European ancestry). Psychopathology was conceptualized hierarchically as empirically derived general factor (p-factor) and five specific factors: externalizing, internalizing, neurodevelopmental, somatoform, and detachment. Partial correlations explored associations between psychopathology factors and 22 psychopathology-related PRSs. Regressions tested which level of the psychopathology hierarchy was most strongly associated with each PRS.
Results
Thirteen PRSs were significantly associated with the general factor, most prominently Chronic Multisite Pain-PRS (r = 0.098), ADHD-PRS (r = 0.079), and Depression-PRS (r = 0.078). After adjusting for the general factor, Depression-PRS, Neuroticism-PRS, PTSD-PRS, Insomnia-PRS, Chronic Back Pain-PRS, and Autism-PRS were not associated with lower order factors. Conversely, several externalizing PRSs, including Adventurousness-PRS and Disinhibition-PRS, remained associated with the externalizing factor (|r| = 0.040–0.058). The ADHD-PRS remained uniquely associated with the neurodevelopmental factor (r = 062).
Conclusions
PRSs developed to predict vulnerability to emotional difficulties and chronic pain generally captured genetic risk for all forms of childhood psychopathology. PRSs developed to predict vulnerability to externalizing difficulties, e.g. disinhibition, tended to be more specific in predicting behavioral problems. The results may inform translation of existing PRSs to pediatric research and future clinical practice.