Dataset Information

Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort.

ABSTRACT:

Importance

The origins and development of autism spectrum disorder (ASD) remain unresolved. No individual-level study has provided estimates of additive genetic, maternal, and environmental effects in ASD across several countries.

Objective

To estimate the additive genetic, maternal, and environmental effects in ASD.

Design, setting, and participants

Population-based, multinational cohort study including full birth cohorts of children from Denmark, Finland, Sweden, Israel, and Western Australia born between January 1, 1998, and December 31, 2011, and followed up to age 16 years. Data were analyzed from September 23, 2016 through February 4, 2018.

Main outcomes and measures

Across 5 countries, models were fitted to estimate variance components describing the total variance in risk for ASD occurrence owing to additive genetics, maternal, and shared and nonshared environmental effects.

Results

The analytic sample included 2 001 631 individuals, of whom 1 027 546 (51.3%) were male. Among the entire sample, 22 156 were diagnosed with ASD. The median (95% CI) ASD heritability was 80.8% (73.2%-85.5%) for country-specific point estimates, ranging from 50.9% (25.1%-75.6%) (Finland) to 86.8% (69.8%-100.0%) (Israel). For the Nordic countries combined, heritability estimates ranged from 81.2% (73.9%-85.3%) to 82.7% (79.1%-86.0%). Maternal effect was estimated to range from 0.4% to 1.6%. Estimates of genetic, maternal, and environmental effects for autistic disorder were similar with ASD.

Conclusions and relevance

Based on population data from 5 countries, the heritability of ASD was estimated to be approximately 80%, indicating that the variation in ASD occurrence in the population is mostly owing to inherited genetic influences, with no support for contribution from maternal effects. The results suggest possible modest differences in the sources of ASD risk between countries.

SUBMITTER: Bai D

PROVIDER: S-EPMC6646998 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAutism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition affecting communication, social interaction, and behavior. Evidence suggests that environmental pollutants are associated with ASD incidence. This review aimed to analyze the effect of environmental pollutants on ASD.MethodsSystematic review and meta-analysis of cohort studies evaluated the association between exposure to environmental pollutants and ASD. We searched COCHRANE CENTRAL, MEDLINE, CINAHL, LILACS, EMBASE, PsycINFO, Web of Science, SciELO, and gray literature from inception to January 2023. The model used for meta-analysis was inverse variance heterogeneity (IVhet). The effect measures were the beta coefficient (β) and the relative risk (RR) with their 95% confidence intervals (95% CI). Sensitivity analyses were carried out using an instrument to screen or diagnose autism.ResultsA total of 5,780 studies were identified; 27 were included in the systematic review, and 22 were included in the meta-analysis. These studies included 1,289,183 participants and 129 environmental pollutants. Individual meta-analyses found a significant association between nitrogen dioxide RR = 1.20 (95% CI: 1.03 to 1.38; I2: 91%), copper RR = 1.08 (95% CI: 1.03 to 1.13; I2: 0%), mono-3-carboxy propyl phthalate β = 0.45 (95% CI: 0.20 to 0.70; I2: 0%), monobutyl phthalate β = 0.43 (95% CI: 0.13 to 0.73; I2: 0%) and polychlorinated biphenyl (PCB) 138 RR = 1.84 (95% CI: 1.14 to 2.96; I2:0%) with ASD. Subgroup meta-analyses found a significant association with carbon monoxide RR = 1.57 (95% CI: 1.25 to 1.97; I2: 0%), nitrogen oxides RR = 1.09 (95% CI: 1.04 to 1.15; I2: 34%) and metals RR = 1.13 (95% CI: 1.01 to 1.27; I2:24%).ConclusionThis study found positive associations nitrogen dioxide, copper, mono-3-carboxypropyl phthalate, monobutyl phthalate, and PCB 138, and the development of ASD, likewise, with subgroups of pollutants carbon monoxide, nitrogen oxides, and metals. Therefore, it is important to identify these risk factors in children and adolescents to contribute to ASD and identify prevention strategies effectively.

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.