Genetic susceptibility to bilateral tinnitus in a Swedish twin cohort.
Ontology highlight
ABSTRACT: Purpose
Genetic contributions to tinnitus have been difficult to determine due to the heterogeneity of the condition and its broad etiology. Here, we evaluated the genetic and nongenetic influences on self-reported tinnitus from the Swedish Twin Registry (STR).Methods
Cross-sectional data from the STR was obtained. Casewise concordance rates (the risk of one twin being affected given that his/her twin partner has tinnitus) were compared for monozygotic (MZ) and dizygotic (DZ) twin pairs (N = 10,464 concordant and discordant twin pairs) and heritability coefficients (the proportion of the total variance attributable to genetic factors) were calculated using biometrical model fitting procedures.Results
Stratification of tinnitus cases into subtypes according to laterality (unilateral versus bilateral) revealed that heritability of bilateral tinnitus was 0.56; however, it was 0.27 for unilateral tinnitus. Heritability was greater in men (0.68) than in women (0.41). However, when female pairs younger than 40 years of age were selected, heritability of 0.62 was achieved with negligible effects of shared environment.Conclusion
Unlike unilateral tinnitus, bilateral tinnitus is influenced by genetic factors and might constitute a genetic subtype. Overall, our study provides the initial evidence for a tinnitus phenotype with a genetic influence.Genet Med advance online publication 23 March 2017.
SUBMITTER: Maas IL
PROVIDER: S-EPMC5589979 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ImportanceNo effective treatments are currently available for severe tinnitus, which affects 1% of the population and lowers the quality of life. The factors that contribute to the transition from mild to severe tinnitus are poorly known. Before performing genetic analyses and determining the mechanisms involved in the development of severe tinnitus, its heritability needs to be determined.ObjectivesTo examine whether clinically significant tinnitus is associated with genetic factors and to evaluate the genetic risk in the transmission of tinnitus using adoptees.Design, setting, and participantsData from adoptees and their biological and adoptive parents from Swedish nationwide registers were collected from January 1, 1964, to December 31, 2015, and used to separate genetic from environmental factors in familial clustering. In all, 11 060 adoptees, 19 015 adoptive parents, and 17 025 biological parents were investigated. The study used a cohort design and a case-control approach to study genetic and nongenetic factors in tinnitus among adoptees.Main outcomes and measuresThe primary outcome was odds ratio (OR) of tinnitus in adoptees with at least 1 affected biological parent compared with adoptees without any affected biological parent using logistic regression. The secondary outcome was OR in adoptees with at least 1 affected adoptive parent compared with adoptees without any affected adoptive parent.ResultsA total of 1029 patients (440 [42.8%] male; mean [SD] age, 62 [14] years) with tinnitus were identified. The prevalence of diagnosed tinnitus was 2.2%. The OR for tinnitus was 2.22 for adoptees (95% CI, 1.03-4.81) of biological parents diagnosed with tinnitus, whereas the OR was 1.00 (95% CI, 0.43-2.32) for adoptees from adoptive parents diagnosed with tinnitus. Mean (SE) heritability determined using tetrachoric correlations was 31% (14%).Conclusions and relevanceThe findings suggest that genetic factors are associated with the familial clustering of clinically significant tinnitus with no shared-environment association, revealing that the transition from negligible to severe tinnitus may be associated with genetic factors. These findings may provide insight for future genetic analyses that focus on severe tinnitus.
| S-EPMC6439751 | biostudies-literature
Project description:Background: A unified or consensus definition of "sustainable working life" remains lacking, although studies investigating risk factors for labour market exit are numerous. In this study, we aimed (1) to update the information and to explore a definition of "sustainable working life" via a systematic literature review and (2) to describe the working life trajectories via the prevalence of sickness absence (SA), disability pension (DP), and unemployment in a Swedish twin cohort to provide a sample overview in our Sustainable Working Life-project. Methods: A systematic literature review was conducted to explore the studies with the search phrase "sustainable working life" in PubMed, PsycInfo, and the Web of Science Database of Social Sciences in January 2021, resulting in a total of 51 references. A qualitative synthesis was performed for the definitions and the measures of "sustainable working life." Based on the Swedish Twin project Of Disability pension and Sickness absence (STODS), the current dataset to address sustainable working life includes 108 280 twin individuals born between 1925 and 1990. Comprehensive register data until 2016 for unemployment, SA and DP were linked to all individuals. Using STODS, we analysed the annual prevalence of SA, DP, and unemployment as working life trajectories over time across education and age groups. Results: The reviewed 16 full articles described several distinct definitions for sustainable working life between 2007 and 2020 from various perspectives, i.e., considering workplaces or employees, the individual, organizational or enterprise level, and the society level. The definition of "sustainable working life" appearing most often was the swAge-model including a broad range of factors, e.g., health, physical/mental/psychosocial work environment, work motivation/satisfaction, and the family situation and leisure activities. Our dataset comprised of 81%-94% of individuals who did not meet SA, DP, or unemployment during the follow-up in 1994-2016, being indicative for "sustainable working life." The annual prevalence across years had a decreasing trend of unemployment over time, whereas the prevalence of SA had more variation, with DP being rather stable. Both unemployment and DP had the highest prevalence among those with a lower level of education, whereas in SA, the differences in prevalence between education levels were minor. Unemployment was highest across the years in the youngest age group (18-27 years), the age group differences for SA were minor, and for DP, the oldest age group (58-65 years) had the highest prevalence. Conclusions: No consensus exists for a "sustainable working life," hence meriting further studies, and we intend to contribute by utilising the STODS database for the Sustainable Working Life project. In the upcoming studies, the existing knowledge of available definitions and frameworks will be utilised. The dataset containing both register data and self-reports enables detailed follow-up for labour market participation for sustainable working life.
| S-EPMC8197988 | biostudies-literature
Project description:A bidirectional association between type 2 diabetes (T2DM) and depression has been consistently reported. Depression is associated with worse biomedical outcomes and increased mortality. The mechanisms underlying the association of T2DM with depression remain unclear. One possible question we can address is the extent to which the co-occurrence of diabetes and depression is due to correlated genetic and/or environmental risk factors. In this study, we performed structural equation model fitting to population-level data from the Swedish (n=68 606) and Danish (n=95 403) twin registries. The primary outcomes were clinical diagnosis of T2DM and depression using national hospital discharge registries. The phenotypic correlation between T2DM and depression is modest in both samples. In the Swedish sample, unique environmental effects explain a greater proportion of the covariance in males, whereas the association is primarily attributed to genetic effects in females. In the Danish sample, genetic effects account for the majority of the covariance in both males and females. Qualitative genetic sex differences are observed in both samples. We believe this is the first study to demonstrate significant genetic overlap between T2DM and depression.
| S-EPMC5414070 | biostudies-literature
Project description:Twin and adoption studies point towards a genetic contribution to tinnitus; however, how the genetic risk applies to different forms of tinnitus is poorly understood. Here, we perform a familial aggregation study and determine the relative recurrence risk for tinnitus in siblings (λs). Four different Swedish studies (N = 186,598) were used to estimate the prevalence of self-reported bilateral, unilateral, constant, and severe tinnitus in the general population and we defined whether these 4 different forms of tinnitus segregate in families from the Swedish Tinnitus Outreach Project (STOP, N = 2305). We implemented a percentile bootstrap approach to provide accurate estimates and confidence intervals for λs. We reveal a significant λs for all types of tinnitus, the highest found being 7.27 (95% CI (5.56-9.07)) for severe tinnitus, with a higher susceptibility in women (10.25; 95% CI (7.14-13.61)) than in men (5.03; 95% CI (3.22-7.01)), suggesting that severity may be the most genetically influenced trait in tinnitus in a sex-dependent manner. Our findings strongly support the notion that genetic factors impact on the development of tinnitus, more so for severe tinnitus. These findings highlight the importance of considering tinnitus severity and sex in the design of large genetic studies to optimize diagnostic approaches and ultimately improve therapeutic interventions.
| S-EPMC7760080 | biostudies-literature
Project description:The heterogeneity of tinnitus is likely accounting for the lack of effective treatment approaches. Headaches have been related to tinnitus, yet little is known on how headaches impact tinnitus. We use cross-sectional data from the Swedish Tinnitus Outreach Project to i) evaluate the association between headaches and tinnitus (n?=?1,984 cases and 1,661 controls) and ii) investigate the phenotypic characteristics of tinnitus subjects with tinnitus (n?=?660) or without (n?=?1,879) headaches. In a multivariable logistic regression model, headache was significantly associated with any tinnitus (odds ratio, OR?=?2.61) and more so with tinnitus as a big problem (as measured by the tinnitus functional index, TFI???48; OR?=?5.63) or severe tinnitus (using the tinnitus handicap inventory, THI???58; OR?=?4.99). When focusing on subjects with tinnitus, the prevalence of headaches was 26% and reached 40% in subjects with severe tinnitus. A large number of socioeconomic, phenotypic and psychological characteristics differed between headache and non-headache subjects with any tinnitus. With increasing tinnitus severity, fewer differences were found, the major ones being vertigo, neck pain and other pain syndromes, as well as stress and anxiety. Our study suggests that headaches could contribute to tinnitus distress and potentially its severity.
| S-EPMC7244494 | biostudies-literature
Project description:The Swedish haemangioma cohort consists of 17,200 women treated with radium-226 for skin haemangioma at an early age (<1.5 years of age) between 1920 and 1965. A total of 877 breast cancer cases were reported by December 2009, estimating an excess relative and absolute risk at the age of 50 years of 0.48 Gy^(−1) and 10.4 (10^4 PYR Gy)^(−1), respectively. We screened 31 primary breast carcinomas for genetic alterations using the OncoScan CNV Plus Assay to assess genomic instability.
2019-04-12 | GSE125700 | GEO
Project description:BACKGROUND:We examined whether childhood conduct problems predicted a wide range of adverse outcomes in emerging adulthood and whether the association with internalizing problems remained after adjusting for general comorbidity and externalizing problems. METHODS:Participants were 18,649 twins from the Child and Adolescent Twin Study in Sweden. At age 9/12, parents rated their children on eight conduct problems. Adverse outcomes were retrieved from national registers in emerging adulthood (median follow-up time = 9.2 years), including diagnoses of six psychiatric disorders, prescriptions of antidepressants, suicide attempts, criminality, high school ineligibility, and social welfare recipiency. We estimated risk for the separate outcomes and examined if conduct problems predicted an internalizing factor above and beyond a general comorbidity and an externalizing factor. We used twin analyses to estimate genetic and environmental contributions to these associations. RESULTS:On the average, each additional conduct symptom in childhood was associated with a 32% increased risk of the adverse outcomes in emerging adulthood (mean hazard ratio = 1.32; range = 1.16, 1.56). A latent childhood conduct problems factor predicted the internalizing factor in emerging adulthood (?boys = .24, standard error, SE = 0.03; ?girls = .17, SE = 0.03), above and beyond its association with the externalizing (?boys = 0.21, SE = 0.04; ?girls = 0.17, SE = 0.05) and general factors (?boys = 0.45, SE = 0.03; ?girls = 0.34, SE = 0.04). These associations were differentially influenced by genetic and environmental factors. CONCLUSIONS:It is important to monitor boys and girls with conduct problems not only for future externalizing problems, but also for future internalizing problems. Prevention of specific outcomes, however, might require interventions at different levels.
| S-EPMC7384167 | biostudies-literature
Project description:ObjectivesTo investigate the association between three poor health behaviours (current smoker, high consumption of alcohol and low physical activity levels) and the transition to disability pension (DP) among individuals who have recently been sickness absent. Furthermore, we aimed to explore whether having multiple poor health behaviours increased the risk of transitioning from sickness absence (SA) to DP.DesignProspective twin cohort study.SettingSweden.ParticipantsTwins aged 20-46 who had participated in a survey and been on SA (>14 days) in the year preceding baseline (date of answering the questionnaire).Main outcome measureIncident DP during the follow-up which ended on 31 December 2012 (mean 5.2 years). A national register with full coverage provided data on DP.ResultsThe Cox proportional-hazards regression analyses showed that current smokers had a higher risk of transitioning from SA to DP compared with never smokers (HR 1.76; 95% CI 1.08 to 2.84). Alcohol use and lack of physical activity as well as poor health behaviour sum score showed no significant associations.ConclusionsBeing a current smoker influences the transition from SA to DP. Although non-significant, there were indications that more physical activity and fewer poor health behaviours could reduce the risk of exiting the labour market through DP. Improving health behaviours among people on SA could be a valuable tool for preventing the transition to DP.
| S-EPMC6858211 | 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:Using Swedish nationwide registry data, the authors investigated genetic and environmental risk factors in the etiology of drug abuse by twin sibling modeling. The authors followed up with epidemiological analyses to identify shared environmental influences on drug abuse.Drug abuse was defined using public medical, legal, or pharmacy records. Twin and sibling pairs were obtained from the national twin and genealogical registers. Information about sibling pair residence within the same household, small residential area, or municipality was obtained from Statistics Sweden. The authors predicted concordance for drug abuse by years of co-residence until the older sibling turned 21 and risk for future drug abuse in adolescents living with parental figures as a function of family-level socioeconomic status and neighborhood social deprivation.The best twin sibling fit model predicted substantial heritability for drug abuse in males (55%) and females (73%), with environmental factors shared by siblings operating only in males and accounting for 23% of the variance in liability. For each year of living in the same household, the probability of sibling concordance for drug abuse increased 2%-5%. When not residing in the same household, concordance was predicted from residence in the same small residential area or municipality. Risk for drug abuse was predicted both by family socioeconomic status and neighborhood social deprivation. Controlling for family socioeconomic status, each year of living in a high social deprivation neighborhood increased the risk for drug abuse by 2%.Using objective registry data, the authors found that drug abuse is highly heritable. A substantial proportion of the shared environmental effect on drug abuse comes from community-wide rather than household-level influences. Genetic effects demonstrated in twin studies have led to molecular analyses to elucidate biological pathways. In a parallel manner, environmental effects can be followed up by epidemiological studies to clarify social mechanisms.
| S-EPMC3927993 | biostudies-literature