Loss of a co-twin at birth and subsequent risk of psychiatric disorders.
Ontology highlight
ABSTRACT:
SUBMITTER: Song H
PROVIDER: S-EPMC7843130 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Loss of a co-twin at birth and subsequent risk of psychiatric disorders.
Song Huan H Fang Fang F Larsson Henrik H Pedersen Nancy L NL Magnusson Patrik Ke PK Almqvist Catarina C Valdimarsdóttir Unnur A UA
eLife 20210128
Twins suffering a co-twin loss at birth have reported feelings of loneliness and grief while it remains unexplored if they suffer increased risk of psychiatric disorders. We contrasted rate of first-onset psychiatric disorders among all Swedish-born twins whose co-twin died within 60 days after birth between 1973 and 2011 (n = 787) to that of 3935 matched unexposed twins, 3935 matched singletons (both matched to the exposed twins by birth year, sex, and birth characteristics), and 880 full sibli ...[more]
Similar Datasets
Project description:Losing a co-twin by death is a severely stressful event yet with unknown impact on the surviving twin's risk of psychiatric disorders. We identified all Swedish-born twins who lost a co-twin by death between 1973 and 2013 (n = 4,528), their 4939 non-twin full siblings, together with 22,640 age- and sex-matched non-bereaved twins. Compared to the non-bereaved twins, exposed twins were at increased risk of receiving a first diagnosis of psychiatric disorders (hazard ratio = 1.65, 95% confidence interval1.48-1.83), particularly during the first month after loss. Similarly, compared to non-twin full siblings, the relative risks were significantly increased after loss of monozygotic co-twin (2.45-fold), and loss of a dizygotic co-twin (1.29-fold), with higher HR observed with greater age gaps between twins and non-twin siblings. As dizygotic twins share equal genetic relatedness to the deceased twin as their full siblings, this pattern suggests that beyond the contribution of genetic factors, shared early life experiences and attachment contribute to the risk of psychiatric disorders among surviving twins after co-twin loss.
| S-EPMC7360364 | biostudies-literature
Project description:We asked if twin birth influences the DNA methylation of subsequent siblings. We measured whole blood methylation using the HumanMethylation450 array for siblings from two twin and family studies in Australia and Korea. We compared the means and correlations in methylation between pairs of siblings born before a twin birth (BT siblings), born on either side of a twin birth (B/AT pairs) and born after a twin birth (AT siblings). For the genome-wide average DNA methylation, the correlation for AT pairs (rAT) was larger than the correlation for BT pairs (rBT) in both studies, and from the meta-analysis, rAT = 0.46 (95% CI: 0.26, 0.63) and rBT = -0.003 (95% CI: -0.30, 0.29) (P = 0.02). B/AT pairs were not correlated (from the meta-analysis rBAT = 0.08; 95% CI: -0.31, 0.45). Similar results were found for the average methylation of several genomic regions, e.g., CpG shelf and gene body. BT and AT pairs were differentially correlated in methylation for 15 probes (all P < 10-7), and the top 152 differentially correlated probes (at P < 10-4) were enriched in cell signalling and breast cancer regulation pathways. Our observations are consistent with a twin birth changing the intrauterine environment such that siblings both born after a twin birth are correlated in DNA methylation.
| S-EPMC5559542 | biostudies-literature
Project description:BackgroundThe association between cardiovascular disease (CVD) and selected psychiatric disorders has frequently been suggested while the potential role of familial factors and comorbidities in such association has rarely been investigated.MethodsWe identified 869,056 patients newly diagnosed with CVD from 1987 to 2016 in Sweden with no history of psychiatric disorders, and 910,178 full siblings of these patients as well as 10 individually age- and sex-matched unrelated population controls (N = 8,690,560). Adjusting for multiple comorbid conditions, we used flexible parametric models and Cox models to estimate the association of CVD with risk of all subsequent psychiatric disorders, comparing rates of first incident psychiatric disorder among CVD patients with rates among unaffected full siblings and population controls.ResultsThe median age at diagnosis was 60 years for patients with CVD and 59.2% were male. During up to 30 years of follow-up, the crude incidence rates of psychiatric disorder were 7.1, 4.6, and 4.0 per 1000 person-years for patients with CVD, their siblings and population controls. In the sibling comparison, we observed an increased risk of psychiatric disorder during the first year after CVD diagnosis (hazard ratio [HR], 2.74; 95% confidence interval [CI], 2.62-2.87) and thereafter (1.45; 95% CI, 1.42-1.48). Increased risks were observed for all types of psychiatric disorders and among all diagnoses of CVD. We observed similar associations in the population comparison. CVD patients who developed a comorbid psychiatric disorder during the first year after diagnosis were at elevated risk of subsequent CVD death compared to patients without such comorbidity (HR, 1.55; 95% CI, 1.44-1.67).ConclusionsPatients diagnosed with CVD are at an elevated risk for subsequent psychiatric disorders independent of shared familial factors and comorbid conditions. Comorbid psychiatric disorders in patients with CVD are associated with higher risk of cardiovascular mortality suggesting that surveillance and treatment of psychiatric comorbidities should be considered as an integral part of clinical management of newly diagnosed CVD patients.FundingThis work was supported by the EU Horizon 2020 Research and Innovation Action Grant (CoMorMent, grant no. 847776 to UV, PFS, and FF), Grant of Excellence, Icelandic Research Fund (grant no. 163362-051 to UV), ERC Consolidator Grant (StressGene, grant no. 726413 to UV), Swedish Research Council (grant no. D0886501 to PFS), and US NIMH R01 MH123724 (to PFS).
| S-EPMC9718522 | biostudies-literature
Project description:Importance:Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes. Objective:To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits. Design, Setting, and Participants:This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017. Main Outcomes and Measures:Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested. Results:Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (β [SE] = 0.04 [0.01] at 9 years of age), ADHD (β [SE] = 0.27 [0.03] at 9 years of age), TDs (β [SE] = 0.02 [0.004] at 9 years of age), OCD (β [SE] = 0.13 [0.05] at 18 years of age), anxiety (β [SE] = 0.18 [0.08] at 9 years of age; β [SE] = 0.07 [0.02] at 15 years of age; and β [SE] = 0.40 [0.17] at 18 years of age), MDD (β [SE] = 0.10 [0.03] at 9 years of age; β [SE] = 0.11 [0.02] at 15 years of age; and β [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (β [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32). Conclusions and Relevance:These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular.
| S-EPMC6439816 | biostudies-other
Project description:ImportancePrevalence of childhood parental death varies by race and ethnicity and socioeconomic status, yet whether similar variation persists in the association with lifetime psychiatric disorder is unknown.ObjectiveTo assess whether race and ethnicity and parental educational attainment are associated with the risk of death of a parent; to determine whether the risk for lifetime psychiatric disorder associated with death of a parent was moderated by race and ethnicity and highest parental educational attainment; and to examine a potential intersection of race and ethnicity with parental educational attainment in the risk of lifetime psychiatric disorder associated with death of a parent.Design, setting, and participantsThis retrospective cohort study used data from the National Comorbidity Study: Adolescent Supplement (NCS-A), 2001 to 2004. Participants included youth aged 13 to 18 years, restricted to Black, Hispanic, and White youth due to power limitations. Data were analyzed from February 26, 2021, to April 21, 2022.ExposureDeath of a parent during childhood.Main outcomes and measuresThe primary study outcome was any lifetime Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) psychiatric disorder, assess via assessed via structured clinical interviews.ResultsAmong 9501 youth (mean [SD] age, 15.2 [1.5] years; 50.9% female), including 511 youth who had experienced parental death and 8990 youth who had not, the cumulative hazard of parental death by age 18 years was approximately doubled for Hispanic (10.1%; 95% CI, 6.9%-14.7%) and Black (14.0%; 95% CI, 10.6%-18.4%) youth compared with White youth (6.0%; 95% CI, 4.7%-7.8%). Similar patterns were noted by parental educational attainment: the cumulative hazard of parental death for youth of parents with less educational attainment was nearly double (10.1%; 95% CI, 8.1%-12.6%) compared with youth of parents with more education (6.6%; 95% CI, 5.2%-8.4%). Death of a parent was positively and significantly associated with risk of any lifetime psychiatric disorder (aOR, 1.34; 95% CI, 1.03-1.75) compared with youth who had not experienced death of a parent. However, this association was not moderated by race and ethnicity (aOR, 1.05; 95% CI, 0.58-1.92) or parental educational attainment (aOR, 1.19; 95%, 0.70-2.04), although power analyses suggest that larger sample sizes are needed.Conclusions and relevanceIn this cross-sectional study, Black and Hispanic youth experienced elevated parental death compared with White youth, yet the risk for any lifetime psychiatric disorder after parental death was not significantly moderated by race and ethnicity or parental education. Both individual- and population-level interventions may be needed to address the increased risk of psychiatric disorders, although additional studies with larger sample sizes are needed.
| S-EPMC9623444 | biostudies-literature
Project description:BackgroundAlthough the death of a child, sibling or spouse has been associated with elevated risk of mortality, less is known about the survival of twin siblings exposed to a co-twin loss.MethodsIn a Swedish population-based sibling-matched cohort, we compared the mortality of 5548 twin individuals who lost their co-twin between 1932 and 2011 with that of 27 740 age-matched and sex-matched twin individuals without such a loss and 6772 full siblings of these exposed twin individuals. Cox regression models were used to estimate the hazard ratios (HRs) of all-cause and cause-specific mortality.ResultsWe found increased risk of all-cause mortality among twin individuals exposed to a co-twin loss compared with matched unexposed twin individuals (HR = 1.30, 95% CI: 1.18-1.43) and their full siblings (HR = 1.10, 95% CI: 0.96-1.27) after adjusting for multiple covariates. The all-cause mortality risk was greater for loss of a co-twin due to unnatural deaths (HR = 1.54, 95% CI: 1.17-2.03) than natural deaths (HR = 1.26, 95% CI: 1.14-1.40). For cause-specific mortality, co-twin loss was associated with a higher risk of unnatural deaths both among twin individuals who lost their co-twin due to unnatural deaths (HR = 1.98, 95% CI: 1.27-3.10) and those whose loss was due to natural deaths (HR = 1.48, 95% CI: 1.07-2.06). The risk elevations were generally stronger for loss of a monozygotic co-twin than loss of a dizygotic co-twin.ConclusionLoss of a co-twin, especially a monozygotic co-twin, was associated with increased mortality, particularly of unnatural causes, among the surviving twin individuals. The excess mortality is likely attributable to both shared disease susceptibility within the twin pair and the adverse health sequelae of bereavement.
| S-EPMC10114119 | biostudies-literature
Project description:Susceptibility genes for Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), monogenetic disorders with intellectual disabilities (ID) or schizophrenia (SCZ) converge on processes related to neuronal function and differentiation. Furthermore, ASD risk genes are enriched for FMRP (Fragile X Mental Retardation Protein) targets and for genes implicated in ID. In addition, a significant co-heritability was observed between ASD and SCZ. The genetic overlap between ASD, FXS, ID and SCZ together with the symptomatic differences gives rise to the question if pathomechanisms impair the same or different regulatory patterns activated during neuronal differentiation (ND). To test this idea, we performed transcriptome analysis of in-vitro differentiation of the neuroblastoma cell line model SH-SY5Y and identified genes that were differentially expressed, dynamically regulated, and coordinately expressed. The identified genetic modules activated during ND are enriched for genetic risk factors for these four disorders. Although risk genes for the disorders significantly overlap, we observed disorder specific enrichments: ASD or FXS implicated genes were likely to be positive regulators of ND whereas ID implicated genes were related to negative regulation. ASD and SCZ genes were specifically enriched among cholesterol and fatty acid associated modules. ID genes were overrepresented among cell cycle modules. In addition, we show that ASD genes are likely to be hub genes. We hypothesize that knowledge about genetic variants of an individual combined with network and pathway context of the related genes will allow differentiating between psychiatric disorders. 21 samples, consisting of 3 replicates harvested at 7 different time-points of RA+BDNF-induced neuronal differentiation
2016-06-01 | E-GEOD-69838 | biostudies-arrayexpress
Project description:BackgroundSeveral psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown.MethodsIn this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N = 875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N = 30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively.FindingsDuring up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79-1.98) and thereafter (1.37; 95% CI, 1.34-1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort.InterpretationIndependent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders.FundingThis research was supported by EU Horizon 2020 Research and Innovation Action Grant, European Research Council Consolidator grant, Icelandic Research fund, Swedish Research Council, US NIMH, the Outstanding Clinical Discipline Project of Shanghai Pudong, the Fundamental Research Funds for the Central Universities, and the European Union through the European Regional Development Fund; the Research Council of Norway; the South-East Regional Health Authority, the Stiftelsen Kristian Gerhard Jebsen, and the EEA-RO-NO-2018-0535.
| S-EPMC10329128 | biostudies-literature
Project description:Human laboratory studies and twin research investigating relationships between alcohol use/pathology and gambling generally have yielded contradictory results, sometimes suggesting causal relationships and common genetic risk factors. 2860 individuals (mean age: 25.60, s.d = 3.21, 50.62% female) from separate clinical (n = 636) and community based (twin) samples (n = 2224) were used to assess associations between past year alcohol use and frequency of past year gambling behaviors (gambling frequency). After adjustment for demographic and psychiatric covariates, individual-level analyses detected that increased alcohol use was associated with more frequent gambling behaviors in twin and clinical samples. Co-twin control models were then used to test potential causal (direct) relationships between alcohol use and gambling frequency. Controlling for all covariates and shared genetic/environmental factors, we found increased alcohol use directly predicted more frequent gambling behaviors (consistent with causality). Our study also suggests shared genetic and/or environmental risk factors contribute to the association between increased alcohol use and frequent gambling behavior, a finding that may be more pronounced in males. The present study helps bridge the gap between twin research and human laboratory studies on gambling and alcohol use and corroborates findings across community and clinical samples. Overall, our findings support both common risk factors between alcohol use and gambling as well as a direct relationship between alcohol use and gambling frequency. Recognizing these dual processes could prove useful for gambling-related prevention/intervention programs.
| S-EPMC7170180 | biostudies-literature
Project description:Postpartum psychiatric disorders are heritable, but how genetic liability varies by other significant risk factors is unknown. We aimed to (1) estimate associations of genetic risk scores (GRS) for major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ) with postpartum psychiatric disorders, (2) examine differences by prior psychiatric history, and (3) compare genetic and familial risk of postpartum psychiatric disorders. We conducted a nested case-control study based on Danish population-based registers of all women in the iPSYCH2012 cohort who had given birth before December 31, 2015 (n = 8850). Cases were women with a diagnosed psychiatric disorder or a filled psychotropic prescription within one year after delivery (n = 5829 cases, 3021 controls). Association analyses were conducted between GRS calculated from Psychiatric Genomics Consortium discovery meta-analyses for MD, BD, and SCZ and case-control status of a postpartum psychiatric disorder. Parental psychiatric history was associated with postpartum psychiatric disorders among women with previous psychiatric history (OR, 1.14; 95% CI 1.02-1.28) but not without psychiatric history (OR, 1.08; 95% CI: 0.81-1.43). GRS for MD was associated with an increased risk of postpartum psychiatric disorders in both women with (OR, 1.44; 95% CI: 1.19-1.74) and without (OR, 1.88; 95% CI: 1.26-2.81) personal psychiatric history. SCZ GRS was only minimally associated with postpartum disorders and BD GRS was not. Results suggest GRS of lifetime psychiatric illness can be applied to the postpartum period, which may provide clues about distinct environmental or genetic elements of postpartum psychiatric disorders and ultimately help identify vulnerable groups.
| S-EPMC6848186 | biostudies-literature