| 1. |
- Andersson, Anneli, 1992-, et al.
(författare)
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Research Review : The strength of the genetic overlap between ADHD and other psychiatric symptoms - a systematic review and meta-analysis
- 2020
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Ingår i: Journal of Child Psychology and Psychiatry. - : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 61:11, s. 1173-1183
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Forskningsöversikt (refereegranskat)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with other psychiatric disorders. Twin studies have established that these co-occurrences are in part due to shared genetic risks. However, the strength of these genetic overlaps and the potential heterogeneity accounted for by type of psychiatric symptoms, age, and methods of assessment remain unclear. We conducted a systematic review to fill this gap.Methods: We searched PubMed, PsycINFO, Embase, and Web of Science until March 07, 2019. Genetic correlations (r(g)) were used as effect size measures.Results: A total of 31 independent studies fulfilled the inclusion criteria. The pooled estimates showed that the associations between ADHD and other psychiatric symptoms were partly explained by shared genetic factors, with a pooled genetic correlation of 0.50, 95% confidence interval: 0.46-0.60. The genetic correlations (r(g)) between ADHD and externalizing (r(g) = .49 [0.37-0.61]), internalizing (r(g) = .50 [0.39-0.69]), and neurodevelopmental (r(g) = .56 [0.47-0.66]) symptoms were similar in magnitude. The genetic correlations in childhood and adulthood werer(g) = .53 (0.43-0.63) andr(g) = .51 (0.44-0.56), respectively. For methods of assessment, the genetic correlations were also similar in strength, self-reportsr(g) = .52 (0.47-0.58), other informantsr(g) = .55 (0.41-0.69), and combined ratersr(g) = .50 (0.33-0.65).Conclusions: These findings indicate that the co-occurrence of externalizing, internalizing, and neurodevelopmental disorder symptoms in individuals with ADHD symptoms in part is due to a shared genetic risk.
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| 2. |
- Brikell, Isabell, et al.
(författare)
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The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:8, s. 1809-1821
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic risk variants have been implicated in the etiology of clinical attention-deficit/hyperactivity disorder (ADHD) diagnoses and symptoms in the general population. However, given the extensive comorbidity across ADHD and other psychiatric conditions, the extent to which genetic variants associated with ADHD also influence broader psychopathology dimensions remains unclear. The aim of this study was to evaluate the associations between ADHD polygenic risk scores (PRS) and a broad range of childhood psychiatric symptoms, and to quantify the extent to which such associations can be attributed to a general factor of childhood psychopathology. We derived ADHD PRS for 13,457 children aged 9 or 12 from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. We estimated associations between ADHD PRS, a general psychopathology factor, and several dimensions of neurodevelopmental, externalizing, and internalizing symptoms, using structural equation modeling. Higher ADHD PRS were statistically significantly associated with elevated neurodevelopmental, externalizing, and depressive symptoms (R 2 = 0.26-1.69%), but not with anxiety. After accounting for a general psychopathology factor, on which all symptoms loaded positively (mean loading = 0.50, range = 0.09-0.91), an association with specific hyperactivity/impulsivity remained significant. ADHD PRS explained ~ 1% (p value < 0.0001) of the variance in the general psychopathology factor and ~ 0.50% (p value < 0.0001) in specific hyperactivity/impulsivity. Our results suggest that common genetic risk variants associated with ADHD, and captured by PRS, also influence a general genetic liability towards broad childhood psychopathology in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.
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| 3. |
- Du Rietz, Ebba, et al.
(författare)
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Associations between ADHD and medical disorders in adulthood : a large-scale genetically informed Swedish register study
- 2020
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 50:6, s. 452-452
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Only a limited number of medical disorders have been thoroughly studied in relation to ADHD, and knowledge is especially lacking for disorders that develop in older ages. This study aimed to map out the phenotypic and aetiologic associations between ADHD and a wide range of medical disorders across adulthood.Full- and maternal half-siblings (N = 4,288,451 pairs), aged 18–81 years, were identified from Swedish Population Registers and linked to ICD-diagnoses from National Patient Registers. Logistic regression was used to estimate associations between ADHD and 35 medical disorders (8 disease groups) within-individuals, and across full- and half-siblings. Quantitative genetic modelling was performed to estimate genetic and environmental contributions to the associations with ADHD.Adults with ADHD had increased risk for most medical disorders (34/35), showing the strongest associations with nervous system (OR = 3.27) and respiratory (OR = 2.49) disease groups. Significantly (P < 0.001) stronger associations were found between full-siblings than half-siblings for nervous system, respiratory, musculoskeletal and metabolic disease groups. Subsequent quantitative genetic modelling showed that these associations with ADHD were largely explained by shared genetic factors, with the exception for nervous system disorders.Individuals with ADHD are at increased risk for a range of medical disorders, with long-term aspects into adult life. While numerous associations between ADHD and medical disorders were largely driven by genetic factors, others, such as nervous system and ageing disorders were mainly driven by individual-specific environmental factors. This mapping of aetiological sources of covariance can guide future research aiming to identify specific mechanisms that contribute to risk for medical disorders in ADHD
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| 4. |
- Du Rietz, Ebba, et al.
(författare)
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Trajectories of healthcare utilization and costs of psychiatric and somatic multimorbidity in adults with childhood ADHD : a prospective register-based study
- 2020
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Ingår i: Journal of Child Psychology and Psychiatry. - : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 61:9, s. 959-968
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Tidskriftsartikel (refereegranskat)abstract
- Background: A better understanding of the trajectories and economic burden of psychiatric and somatic disorders (multimorbidity) in ADHD from childhood to adulthood is important for guiding more targeted areas for treatment of ADHD and prevention of multimorbidity, and for forecasting demands on the medical infrastructure. This study aimed to investigate patterns of healthcare utilization and costs of multimorbidity across young adulthood in individuals with a childhood ADHD diagnosis, and additionally in individuals who continue to have ADHD-related contact with health services (persisters) and those who do not (remitters).Methods: We prospectively followed a cohort (N = 445,790) born 1987-1990 from the ages of 18 to 26 years. Data on healthcare utilization were obtained from the Swedish National Patient Register (inpatient and outpatient care) and the Prescribed Drug Register (medication prescriptions).Results: Mean annual costs per capita from multimorbidity was euro890 ($1,223) in individuals with a childhood ADHD diagnosis (persisters/remitters: euro1,060[$1,456]/euro609[$837]) and euro304 ($418) in individuals without. Costs were largely driven by inpatient hospital admissions, mainly from drug abuse and injuries. Healthcare utilization and costs of psychiatric and somatic disorders at 18 years was significantly higher in individuals with childhood ADHD compared to those without. These group differences remained stable or increased across young adulthood for most outcomes and were generally larger in women than in men. ADHD remitters continued to show significantly greater healthcare utilization and costs compared to individuals without childhood ADHD, although their profiles were not as severe as ADHD persisters.Conclusions: Childhood ADHD has long-term associations with both psychiatric and somatic disorders. Findings demonstrate the individual and societal burden of ADHD in adulthood and highlight the importance of continued support from childhood-adolescent to adult health services and early prevention of multimorbidity. Findings also point to specific targets for intervention that may be effective, such as drug abuse and injuries.
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| 5. |
- Esberg, Anders, et al.
(författare)
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Heritability of Oral Microbiota and Immune Responses to Oral Bacteria
- 2020
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Maintaining a symbiotic oral microbiota is essential for oral and dental health, and host genetic factors may affect the composition or function of the oral microbiota through a range of possible mechanisms, including immune pathways. The study included 836 Swedish twins divided into separate groups of adolescents (n= 418) and unrelated adults (n= 418). Oral microbiota composition and functions of non-enzymatically lysed oral bacteria samples were evaluated using 16S rRNA gene sequencing and functional bioinformatics tools in the adolescents. Adaptive immune responses were assessed by testing for serum IgG antibodies against a panel of common oral bacteria in adults. In the adolescents, host genetic factors were associated with both the detection and abundance of microbial species, but with considerable variation between species. Host genetic factors were associated with predicted microbiota functions, including several functions related to bacterial sucrose, fructose, and carbohydrate metabolism. In adults, genetic factors were associated with serum antibodies against oral bacteria. In conclusion, host genetic factors affect the composition of the oral microbiota at a species level, and host-governed adaptive immune responses, and also affect the concerted functions of the oral microbiota as a whole. This may help explain why some people are genetically predisposed to the major dental diseases of caries and periodontitis.
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| 6. |
- Ghirardi, Laura, et al.
(författare)
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Use of medication for attention-deficit/hyperactivity disorder and risk of unintentional injuries in children and adolescents with co-occurring neurodevelopmental disorders
- 2020
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Ingår i: Journal of Child Psychology and Psychiatry. - : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 61:2, s. 140-147
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often associated with other neurodevelopmental disorders (NDs) and with risky behaviors and adverse health outcomes, including injuries. Treatment with ADHD medication has been associated with reduced risk of injuries. However, it is unknown whether the association is present in individuals with co-occurring NDs. The aim of the present study was to estimate the association between ADHD medication use and unintentional injuries in Sweden in children and adolescents with ADHD, including those with co-occurring NDs.METHODS: Using a linkage of several national registers via the unique personal identification number, we identified individuals with a diagnosis of ADHD and of other NDs, including autism spectrum disorder, intellectual disability, communication disorders, learning disorders and motor disorders. The primary outcome was unintentional injuries. Secondary outcome was traumatic brain injury (TBI). Individuals were followed from January 1st 2006 or their 5th birthday or the date of the first unintentional injury, whichever came last, to December 31st 2013 or their 18th birthday or death, whichever came first. We compared the rate of injuries during periods on-treatment with the rate of injuries during periods off-treatment within the same individual using stratified Cox regression to calculate hazard ratio (HR) with 95% confidence intervals (CIs).RESULTS: For children and adolescents with ADHD (N = 9,421) the rate of any unintentional injuries (HR = 0.85; 95% CI = 0.78-0.92) and TBIs (HR = 0.27; 95% CIs = 0.20-0.38) during medicated periods was lower than during non-medicated periods. Similar results were found among individuals with co-occurring NDs (N = 2,986), for unintentional injuries (HR = 0.88; 95% CI = 0.77-1.01) and for TBIs (HR = 0.27; 95% CI = 0.16-0.44).CONCLUSIONS: Beneficial effects of ADHD medication may extend beyond reduction of ADHD core symptoms to prevention of unintentional injuries in children and adolescents, including individuals with co-occurring NDs.
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| 7. |
- Holowko, Natalie, et al.
(författare)
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Heritability of mammographic breast density, density change, microcalcifications, and masses
- 2020
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Ingår i: Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0008-5472. ; 80:7, s. 1590-1600
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mammographic features influence breast cancer risk and are used in risk prediction models. Understanding how genetics influence mammographic features is important since the mechanisms through which they are associated with breast cancer are not well known. Methods: Mammographic screening history and detailed questionnaire data for 56,820 women from the KARMA prospective cohort study were used. The heritability of mammographic features such as dense area (MD), microcalcifications, masses, and density change (MDC – cm2/year) were estimated using 1,940 sister pairs. We investigated the association between a genetic predisposition to breast cancer and mammographic features, among women with family history of breast cancer information (N=49,674) and a polygenic risk score (PRS, N=9,365). Results: Heritability was estimated at 58% (95% CI: 48%, 67%) for MD, 23% (2%, 45%) for microcalcifications, and 13% (1%, 25%) for masses. The estimated heritability for MDC was essentially null (2%, 95% CI: -8%, 12%). The association between a genetic predisposition to breast cancer (using PRS) and MD and microcalcifications was positive, while for masses this was borderline significant. In addition, for MDC, having a family history of breast cancer was associated with slightly greater MD reduction. Conclusions: We confirmed previous findings of heritability in MD, and also found heritability of the number of microcalcifications and masses at baseline. Since these features are associated with breast cancer risk, and can improve detecting women at short-term risk of breast cancer, further investigation of common loci associated with mammographic features is warranted to better understand the etiology of breast cancer.
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| 8. |
- Khemiri, Lotfi, et al.
(författare)
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Association of parental substance use disorder with offspring cognition : a population family-based study
- 2020
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Ingår i: Addiction. - : Blackwell Publishing. - 0965-2140 .- 1360-0443. ; 115:2, s. 326-336
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors.DESIGN: A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins).SETTING AND PARTICIPANTS: A total of 3 004 401 people born in Sweden between 1951 and 1998.MEASUREMENTS: The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses.FINDINGS: In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors.CONCLUSIONS: There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.
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| 9. |
- Li, Lin, 1989-, et al.
(författare)
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Attention-deficit/hyperactivity disorder symptoms and dietary habits in adulthood : A large population-based twin study in Sweden
- 2020
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Ingår i: American Journal of Medical Genetics Part B. - : John Wiley & Sons. - 1552-4841 .- 1552-485X. ; 183:8, s. 475-485
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Tidskriftsartikel (refereegranskat)abstract
- Associations between adult attention-deficit/hyperactivity disorder (ADHD) symptoms and dietary habits have not been well established and the underlying mechanisms remain unclear. We explored these associations using a Swedish population-based twin study with 17,999 individuals aged 20-47 years. We estimated correlations between inattention and hyperactivity/impulsivity with dietary habits and fitted twin models to determine the genetic and environmental contributions. Dietary habits were defined as (a) consumption of food groups, (b) consumption of food items rich in particular macronutrients, and (c) healthy and unhealthy dietary patterns. At the phenotypic level, inattention was positively correlated with seafood, high-fat, high-sugar, high-protein food consumptions, and unhealthy dietary pattern, with correlation coefficients ranging from 0.03 (95%CI: 0.01, 0.05) to 0.13 (95% CI: 0.11, 0.15). Inattention was negatively correlated with fruits, vegetables consumptions and healthy dietary pattern, with correlation coefficients ranging from -0.06 (95%CI: -0.08, -0.04) to -0.07 (95%CI: -0.09, -0.05). Hyperactivity/impulsivity and dietary habits showed similar but weaker patterns compared to inattention. All associations remained stable across age, sex and socioeconomic status. Nonshared environmental effects contributed substantially to the correlations of inattention (56-60%) and hyperactivity/impulsivity (63-80%) with dietary habits. The highest and lowest genetic correlations were between inattention and high-sugar food (rA = .16, 95% CI: 0.07, 0.25), and between hyperactivity/impulsivity and unhealthy dietary pattern (rA = .05, 95% CI: -0.05, 0.14), respectively. We found phenotypic and etiological overlap between ADHD and dietary habits, although these associations were weak. Our findings contribute to a better understanding of common etiological pathways between ADHD symptoms and various dietary habits.
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| 10. |
- O'Reilly, Lauren M., et al.
(författare)
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The intergenerational transmission of suicidal behavior : an offspring of siblings study
- 2020
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We examined the extent to which genetic factors shared across generations, measured covariates, and environmental factors associated with parental suicidal behavior (suicide attempt or suicide) account for the association between parental and offspring suicidal behavior. We used a Swedish cohort of 2,762,883 offspring born 1973-2001. We conducted two sets of analyses with offspring of half- and full-siblings: (1) quantitative behavior genetic models analyzing maternal suicidal behavior and (2) fixed-effects Cox proportional hazard models analyzing maternal and paternal suicidal behavior. The analyses also adjusted for numerous measured covariates (e.g., parental severe mental illness). Quantitative behavior genetic analyses found that 29.2% (95% confidence interval [CI], 5.29, 53.12%) of the intergenerational association was due to environmental factors associated with exposure to maternal suicidal behavior, with the remainder due to genetic factors. Statistical adjustment for parental behavioral health problems partially attenuated the environmental association; however, the results were no longer statistically significant. Cox hazard models similarly found that offspring were at a 2.74-fold increased risk [95% CI, 2.67, 2.83]) of suicidal behavior if their mothers attempted/died by suicide. After adjustment for familial factors and measured covariates, associations attenuated but remained elevated for offspring of discordant half-siblings (HR, 1.57 [95% CI, 1.45, 1.71]) and full-siblings (HR, 1.62 [95% CI, 1.57, 1.67]). Cox hazard models demonstrated a similar pattern between paternal and offspring suicidal behavior. This study found that the intergenerational transmission of suicidal behavior is largely due to shared genetic factors, as well as factors associated with parental behavioral health problems and environmental factors associated with parental suicidal behavior.
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