-
Frontiers in Clinical Diabetes and... 2023Comorbidity between depression and type 2 diabetes is thought to arise from the joint effects of psychological, behavioral, and biological processes. Studies of...
Leveraging a genetically-informative study design to explore depression as a risk factor for type 2 diabetes: Rationale and participant characteristics of the Mood and Immune Regulation in Twins Study.
BACKGROUND
Comorbidity between depression and type 2 diabetes is thought to arise from the joint effects of psychological, behavioral, and biological processes. Studies of monozygotic twins may provide a unique opportunity for clarifying how these processes inter-relate. This paper describes the rationale, characteristics, and initial findings of a longitudinal co-twin study aimed at examining the biopsychosocial mechanisms linking depression and risk of diabetes in mid-life.
METHODS
Participants in the Mood and Immune Regulation in Twins (MIRT) Study were recruited from the Mid-Atlantic Twin Registry. MIRT consisted of 94 individuals who do not have diabetes at baseline, representing 43 twin pairs (41 monozygotic and 2 dizygotic), one set of monozygotic triplets, and 5 individuals whose co-twin did not participate. A broad set of variables were assessed including (e.g., lifetime history major depression (MD)); (e.g., stress perceptions and experiences); and , including indicators of metabolic risk (e.g., BMI, blood pressure (BP), HbA1c) and immune functioning (e.g., pro- and anti-inflammatory cytokines), as well as collection of RNA. Participants were re-assessed 6-month later. Intra-class correlation coefficients (ICC) and descriptive comparisons were used to explore variation in these psychological, social, and biological factors across time and within pairs.
RESULTS
Mean age was 53 years, 68% were female, and 77% identified as white. One-third had a history of MD, and 18 sibling sets were discordant for MD. MD was associated with higher systolic (139.1 vs 132.2 mmHg, p=0.05) and diastolic BP (87.2 vs. 80.8 mmHg, p=0.002) and IL-6 (1.47 vs. 0.93 pg/mL, p=0.001). MD was not associated with BMI, HbA1c, or other immune markers. While the biological characteristics of the co-twins were significantly correlated, all within-person ICCs were higher than the within-pair correlations (e.g., HbA1c within-person ICC=0.88 vs. within-pair ICC=0.49; IL-6 within-person ICC=0.64 vs. within-pair=0.54). Among the pairs discordant for MD, depression was not substantially associated with metabolic or immune markers, but was positively associated with stress.
CONCLUSIONS
Twin studies have the potential to clarify the biopsychosocial processes linking depression and diabetes, and recently completed processing of RNA samples from MIRT permits future exploration of gene expression as a potential mechanism.
PubMed: 37008275
DOI: 10.3389/fcdhc.2023.1026402 -
Can frailty scores predict the incidence of cancer? Results from two large population-based studies.GeroScience Jun 2023While chronological age is the single biggest risk factor for cancer, it is less clear whether frailty, an age-related state of physiological decline, may also predict...
While chronological age is the single biggest risk factor for cancer, it is less clear whether frailty, an age-related state of physiological decline, may also predict cancer incidence. We assessed the associations of frailty index (FI) and frailty phenotype (FP) scores with the incidence of any cancer and five common cancers (breast, prostate, lung, colorectal, melanoma) in 453,144 UK Biobank (UKB) and 36,888 Screening Across the Lifespan Twin study (SALT) participants, who aged 38-73 years and had no cancer diagnosis at baseline. During a median follow-up of 10.9 and 10.7 years, 53,049 (11.7%) and 4,362 (11.8%) incident cancers were documented in UKB and SALT, respectively. Using multivariable-adjusted Cox models, we found a higher risk of any cancer in frail vs. non-frail UKB participants, when defined by both FI (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.17-1.28) and FP (HR = 1.16; 95% CI = 1.11-1.21). The FI in SALT similarly predicted risk of any cancer (HR = 1.31; 95% CI = 1.15-1.49). Moreover, frailty was predictive of lung cancer in UKB, although this association was not observed in SALT. Adding frailty scores to models including age, sex, and traditional cancer risk factors resulted in little improvement in C-statistics for most cancers. In a within-twin-pair analysis in SALT, the association between FI and any cancer was attenuated within monozygotic but not dizygotic twins, indicating that it may partly be explained by genetic factors. Our findings suggest that frailty scores are associated with the incidence of any cancer and lung cancer, although their clinical utility for predicting cancers may be limited.
Topics: Humans; Male; Aged; Frailty; Frail Elderly; Incidence; Longevity; Lung Neoplasms
PubMed: 36997701
DOI: 10.1007/s11357-023-00783-9 -
Medicina (Kaunas, Lithuania) Mar 2023: This study aimed to compare maternal complications, perinatal outcomes, and neurodevelopment 1 year after the birth between concordant and discordant twins in...
: This study aimed to compare maternal complications, perinatal outcomes, and neurodevelopment 1 year after the birth between concordant and discordant twins in monochorionic and dichorionic twins. : This retrospective study included twin pregnancies delivered between 24 + 1 and 38 + 2 weeks of gestation between January 2011 and September 2019. Chorionicity was confirmed by ultrasonography and was categorized into monochorionic and dichorionic. Each was then divided into two groups (concordant and discordant) according to birth weight discordancy. Maternal complications and neonatal outcomes, including neurodevelopmental delays, were compared between the two groups. : A total of 298 pairs of twin pregnancies were enrolled, of which 58 (19.26%) women were pregnant with monochorionic diamniotic twins and 240 (80.54%) with dichorionic diamniotic twins. In both monochorionic and dichorionic twins, the discordant twins had a greater incidence of emergency deliveries because of iatrogenic causes than the concordant twins. Among dichorionic twins, discordant twins had lower birth weight rates and higher hospitalization rates and morbidities than concordant twins. Among monochorionic twins, discordant twins had a lower birth weight and higher neonatal mortality than concordant twins. The neonatal size was not a predictor of neurodevelopment in this group. Based on the logistic regression analysis, male sex, respiratory distress syndrome, and bronchopulmonary dysplasia were risk factors for the neurodevelopmental delay; birth weight discordancy was significant only in dichorionic twins. : Perinatal outcomes in discordant twins may be poor, and neurodevelopment 1 year after birth was worse in discordant twins than in concordant twins. Discordancy in twins can be a risk factor for neurodevelopmental delay.
Topics: Pregnancy; Infant, Newborn; Male; Humans; Female; Birth Weight; Retrospective Studies; Twins, Dizygotic; Pregnancy, Twin; Pregnancy Complications; Twins, Monozygotic
PubMed: 36984492
DOI: 10.3390/medicina59030493 -
Acta Obstetricia Et Gynecologica... May 2023Twin pregnancies have significantly higher rates of perinatal morbidity and mortality compared to singleton pregnancies; current attempts to reduce perinatal mortality... (Observational Study)
Observational Study
INTRODUCTION
Twin pregnancies have significantly higher rates of perinatal morbidity and mortality compared to singleton pregnancies; current attempts to reduce perinatal mortality have been less successful in twin pregnancies. The paucity of information about modifiable risk factors for adverse neonatal outcomes in twin pregnancies, as well as independent effects of chorionicity may have contributed to this outcome. This study aimed to explore the feasibility of an observational study to identify modifiable factors associated with adverse neonatal outcomes in twin pregnancies.
MATERIAL AND METHODS
Patients pregnant with twins at six UK hospitals between December 2019-March 2021 completed researcher-administered questionnaires at approximately 20-, 28- and 36-weeks' gestation, recording a wide range of self-reported social, lifestyle and demographic factors, alongside prospectively recorded clinical data from maternity records. Descriptive statistics were used to describe frequencies of exposures; logistic regression was used to determine whether factors were associated with a composite measure of adverse neonatal outcome.
RESULTS
Data were collected from 65% (181/277) of eligible participants. A total of 98% (175) of participants had positive views about their participation. Some exposures, including cigarette smoking, supine sleep position and reduced fetal movements were less frequent in twin pregnancies compared to singletons, whereas fertility treatment was more common. Furthermore, different patterns of exposure were seen between monochorionic and dichorionic twins. This pilot study found some associations with adverse neonatal outcomes including: low BMI (OR 8.36, 95% CI: 1.02-68.87), maternal age ≥41 years (OR 9.0 95% CI: 1.07-75.84), maternally perceived high-stress levels (OR 1.96, 95% CI: 1.03-3.75) and inadequate antenatal screening (OR 1.44, 95% CI: 1.01-2.06). Sleep duration ≥9 h and right-sided going to sleep position were more frequent among pregnancies with adverse outcomes. Participants who reported receiving no information on fetal movement and reduced maternal perception of movements were more likely to have an adverse outcome, but sample size prohibited analysis based upon chorionicity.
CONCLUSIONS
An observational study of modifiable factors in twin pregnancy is feasible. Differences in the frequencies of exposures between twin and singleton pregnancies highlight the need for twin-specific studies to identify modifiable factors and develop preventative strategies for morbidity and mortality in twin pregnancies.
Topics: Adult; Female; Humans; Infant, Newborn; Pregnancy; Feasibility Studies; Gestational Age; Pilot Projects; Pregnancy Outcome; Pregnancy, Twin; Retrospective Studies; Twins, Dizygotic
PubMed: 36961126
DOI: 10.1111/aogs.14540 -
Obesity Facts 2023While the genetic and environmental underpinnings of body weight and alcohol use are fairly well-known, determinants of simultaneous changes in these traits are still...
INTRODUCTION
While the genetic and environmental underpinnings of body weight and alcohol use are fairly well-known, determinants of simultaneous changes in these traits are still poorly known. We sought to quantify the environmental and genetic components underlying parallel changes in weight and alcohol consumption and to investigate potential covariation between them.
METHODS
The analysis comprised 4,461 adult participants (58% women) from the Finnish Twin Cohort with four measures of alcohol consumption and body mass index (BMI) over a 36-year follow-up. Trajectories of each trait were described by growth factors, defined as intercepts (i.e., baseline) and slopes (i.e., change over follow-up), using latent growth curve modeling. Growth values were used for male (190 monozygotic pairs, 293 dizygotic pairs) and female (316 monozygotic pairs, 487 dizygotic pairs) same-sex complete twin pairs in multivariate twin modeling. The variances and covariances of growth factors were then decomposed into genetic and environmental components.
RESULTS
The baseline heritabilities were similar in men (BMI: h2 = 79% [95% confidence interval: 74, 83]; alcohol consumption: h2 = 49% [32, 67]) and women (h2 = 77% [73, 81]; h2 = 45% [29, 61]). Heritabilities of BMI change were similar in men (h2 = 52% [42, 61]) and women (h2 = 57% [50, 63]), but the heritability of change in alcohol consumption was significantly higher (p = 0.03) in men (h2 = 45% [34, 54]) than in women (h2 = 31% [22, 38]). Significant additive genetic correlations between BMI at baseline and change in alcohol consumption were observed in both men (rA = -0.17 [-0.29, -0.04]) and women (rA = -0.18 [-0.31, -0.06]). Non-shared environmental factors affecting changes in alcohol consumption and BMI were correlated in men (rE = 0.18 [0.06, 0.30]). Among women, non-shared environmental factors affecting baseline alcohol consumption and the change in BMI were inversely correlated (rE = -0.11 [-0.20, -0.01]).
CONCLUSIONS
Based on genetic correlations, genetic variation underlying BMI may affect changes in alcohol consumption. Independent of genetic effects, change in BMI correlates with change in alcohol consumption in men, suggesting direct effects between them.
Topics: Adult; Female; Humans; Male; Alcohol Drinking; Body Mass Index; Cohort Studies; Longitudinal Studies; Twins, Dizygotic; Twins, Monozygotic
PubMed: 36882010
DOI: 10.1159/000529835 -
Frontiers in Psychiatry 2023The rapid spread of the new Coronavirus and the consequent restrictions to contain transmission generated an unprecedented psychological impact on the general...
BACKGROUND
The rapid spread of the new Coronavirus and the consequent restrictions to contain transmission generated an unprecedented psychological impact on the general population. The Italian Twin Registry performed a longitudinal study to investigate to what extent genetic and environmental influences contributed to changes in depressive symptoms.
METHODS
Data from adult twins were collected. All participants completed an online questionnaire including the 2-item Patient Health Questionnaire (PHQ-2) just before (February 2020) and immediately after the Italian lockdown (June 2020). Genetic modeling based on Cholesky decomposition was used to estimate the role of genetic (A) and both shared (C) and unshared (E) environmental factors in the observed longitudinal course of depressive symptoms.
RESULTS
Longitudinal genetic analysis was based on 348 twin pairs (215 monozygotic and 133 dizygotic pairs) with a mean age of 42.6 years (range 18-93 years). An AE Cholesky model provided heritability estimates for depressive symptoms of 0.24 and 0.35 before and after the lockdown period, respectively. Under the same model, the observed longitudinal trait correlation (0.44) was approximately equally contributed by genetic (46%) and unshared environmental (54%) influences, while longitudinal environmental correlation was lower than genetic correlation (0.34 and 0.71, respectively).
CONCLUSIONS
Although the heritability of depressive symptoms was rather stable across the targeted time window, different environmental as well as genetic factors seemed to act before and after the lockdown, which suggests possible gene-environment interaction.
PubMed: 36860500
DOI: 10.3389/fpsyt.2023.954737 -
Cureus Jan 2023Sirenomelia, also known as "mermaid syndrome" or "mermaid baby syndrome," is a very rare congenital disorder. The major anomaly in this syndrome is the fusion of the...
Sirenomelia, also known as "mermaid syndrome" or "mermaid baby syndrome," is a very rare congenital disorder. The major anomaly in this syndrome is the fusion of the lower legs, giving it a mermaid-like appearance. This syndrome consists of a range of abnormalities affecting various systems, such as the digestive, genitourinary, and musculoskeletal systems. On the basis of the severity of the syndrome, the fetus may have a single fused bone or entirely absent bones in place of a normal pair of distinct bones. In major cases, mermaid syndrome leads to stillbirths. Its occurrence in monozygotic twins is much greater than in dizygotic twins or in a single fetus. The syndrome is believed to mainly occur in cases of maternal age less than 20 years or more than 40 years, women suffering from maternal diabetes, and prenatal exposure to retinoic acid, cocaine, and water contaminated by landfills. A 22-year-old pregnant female was admitted with a history of amenorrhea for nine months (full-term twin pregnancy) and oligohydramnios for a caesarian section. This was the patient's second pregnancy. A cesarean section was done as instructed by the gynecologist. The patient delivered twin babies. In this twin pregnancy, the first baby was normal and healthy, while the second baby was stillborn and suffered from mermaid syndrome.
PubMed: 36860221
DOI: 10.7759/cureus.34311 -
PLoS Genetics Feb 2023X-chromosome inactivation (XCI) silences one X in female cells to balance sex-differences in X-dosage. A subset of X-linked genes escape XCI, but the extent to which...
X-chromosome inactivation (XCI) silences one X in female cells to balance sex-differences in X-dosage. A subset of X-linked genes escape XCI, but the extent to which this phenomenon occurs and how it varies across tissues and in a population is as yet unclear. To characterize incidence and variability of escape across individuals and tissues, we conducted a transcriptomic study of escape in adipose, skin, lymphoblastoid cell lines and immune cells in 248 healthy individuals exhibiting skewed XCI. We quantify XCI escape from a linear model of genes' allelic fold-change and XIST-based degree of XCI skewing. We identify 62 genes, including 19 lncRNAs, with previously unknown patterns of escape. We find a range of tissue-specificity, with 11% of genes escaping XCI constitutively across tissues and 23% demonstrating tissue-restricted escape, including cell type-specific escape across immune cells of the same individual. We also detect substantial inter-individual variability in escape. Monozygotic twins share more similar escape than dizygotic twins, indicating that genetic factors may underlie inter-individual differences in escape. However, discordant escape also occurs within monozygotic co-twins, suggesting environmental factors also influence escape. Altogether, these data indicate that XCI escape is an under-appreciated source of transcriptional differences, and an intricate phenotype impacting variable trait expressivity in females.
Topics: Humans; Female; X Chromosome Inactivation; Chromosomes, Human, X; Genes, X-Linked; Twins, Monozygotic; Phenotype
PubMed: 36802379
DOI: 10.1371/journal.pgen.1010556 -
Age and Ageing Feb 2023Sarcopenia, characterised by an accelerated loss of skeletal muscle mass and function, is associated with negative outcomes. This study aimed to evaluate factors...
BACKGROUND
Sarcopenia, characterised by an accelerated loss of skeletal muscle mass and function, is associated with negative outcomes. This study aimed to evaluate factors associated with skeletal muscle strength, mass and sarcopenia, particularly protein intake, and to assess whether shared twin characteristics are important.
METHODS
This study utilised cross-sectional data from a study of community-dwelling twins aged ≥60 years. Multivariable logistic regression and between- and within-twin pair regression modelling were used.
RESULTS
Participants (n = 3,302) were 89% female (n = 2,923), aged a mean of 72.1 (±7.3) years and composed of 858 (55%) monozygotic, 709 (45%) dizygotic twin pairs and 168 individual lone twins. Using optimal protein intake as the reference group (1.0-1.3 g/kg/day), there was no significant association between protein intake (neither high nor low) and low muscle strength, or between low protein intake and sarcopenia (odds ratio (OR) 0.7; 95% confidence interval (CI) 0.39-1.25; P = 0.229) in unadjusted models. High protein intake (>1.3 g/kg/day) was associated with low muscle mass (OR 1.76; 95% CI 1.39-2.24; P < 0.0001), while low protein intake was protective (OR 0.52; 95% CI 0.40-0.67; P < 0.0001). High protein intake was associated with sarcopenia (OR 2.04; 95% CI 1.21-3.44; P = 0.008), and this was robust to adjustment for demographic, anthropometric and dietary factors. The association between muscle strength and weight, body mass index, healthy eating index, protein intake and alpha diversity was not significantly influenced by shared twin factors, indicating greater amenability to interventions.
CONCLUSIONS
High protein intake is associated with sarcopenia in a cohort of healthy older twins.
Topics: Aged; Female; Humans; Male; Cross-Sectional Studies; Dietary Proteins; Muscle Strength; Muscle, Skeletal; Sarcopenia
PubMed: 36800504
DOI: 10.1093/ageing/afad018 -
Gene-by-Environment Interaction Effects of Social Adversity on Externalizing Behavior in ABCD Youth.Behavior Genetics May 2023This study tested whether multiple domains of social adversity, including neighborhood opportunity/deprivation and life stress, moderate genetic (A), common...
This study tested whether multiple domains of social adversity, including neighborhood opportunity/deprivation and life stress, moderate genetic (A), common environmental (C), and unique environmental (E) influences on externalizing behaviors in 760 same-sex twin pairs (332 monozygotic; 428 dizygotic) ages 10-11 from the ABCD Study. Proportion of C influences on externalizing behavior increased at higher neighborhood adversity (lower overall opportunity). A decreased and C and E increased at lower levels of educational opportunity. A increased at lower health-environment and social-economic opportunity levels. For life stress, A decreased and E increased with number of experienced events. Results for educational opportunity and stressful life experiences suggest a bioecological gene-environment interaction pattern such that environmental influences predominate at higher levels of adversity, whereas limited access to healthcare, housing, and employment stability may potentiate genetic liability for externalizing behavior via a diathesis-stress mechanism. More detailed operationalization of social adversity in gene-environment interaction studies is needed.
Topics: Adolescent; Child; Humans; Environment; Gene-Environment Interaction; Social Environment; Twins, Dizygotic; Twins, Monozygotic
PubMed: 36795263
DOI: 10.1007/s10519-023-10136-z