| 1. |
- Mahjani, Behrang, et al.
(författare)
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The Genetic Architecture of Obsessive-Compulsive Disorder: Contribution of Liability to OCD From Alleles Across the Frequency Spectrum.
- 2022
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 179:3
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Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of genetic variation across the allele frequency spectrum to this heritability remains uncertain. The authors used two new homogeneous cohorts to estimate the heritability of OCD from inherited genetic variation and contrasted the results with those of previous studies.The sample consisted of 2,090 Swedish-born individuals diagnosed with OCD and 4,567 control subjects, all genotyped for common genetic variants, specifically >400,000 single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥0.01. Using genotypes of these SNPs to estimate distant familial relationships among individuals, the authors estimated the heritability of OCD, both overall and partitioned according to MAF bins.Narrow-sense heritability of OCD was estimated at 29% (SE=4%). The estimate was robust, varying only modestly under different models. Contrary to an earlier study, however, SNPs with MAF between 0.01 and 0.05 accounted for 10% of heritability, and estimated heritability per MAF bin roughly followed expectations based on a simple model for SNP-based heritability.These results indicate that common inherited risk variation (MAF ≥0.01) accounts for most of the heritable variation in OCD. SNPs with low MAF contribute meaningfully to the heritability of OCD, and the results are consistent with expectation under the "infinitesimal model" (also referred to as the "polygenic model"), where risk is influenced by a large number of loci across the genome and across MAF bins.
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| 2. |
- Mahjani, Behrang, et al.
(författare)
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Direct additive genetics and maternal effect contribute to the risk of Tourette disorder
- 2023
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 94:8, s. 638-642
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Risk for Tourette disorder, and chronic motor or vocal tic disorders (referenced here inclusively as CTD), arise from a combination of genetic and environmental factors. While multiple studies have demonstrated the importance of direct additive genetic variation for CTD risk, little is known about the role of cross-generational transmission of genetic risk, such as maternal effect, which is not transmitted via the inherited parental genomes. Here, we partition sources of variation on CTD risk into direct additive genetic effect (narrow-sense heritability) and maternal effect.METHODS: The study population consists of 2 522 677 individuals from the Swedish Medical Birth Register, who were born in Sweden between 1 January 1973 and 31 December 2000, and followed for a diagnosis of CTD through 31 December, 2013. We used generalised linear mixed models to partition the liability of CTD into: direct additive genetic effect, genetic maternal effect and environmental maternal effect.RESULTS: We identified 6227 (0.2%) individuals in the birth cohort with a CTD diagnosis. A study of half-siblings showed that maternal half-siblings had twice higher risk of developing a CTD compared with paternal ones. We estimated 60.7% direct additive genetic effect (95% credible interval, 58.5% to 62.4%), 4.8% genetic maternal effect (95% credible interval, 4.4% to 5.1%) and 0.5% environmental maternal effect (95% credible interval, 0.2% to 7%).CONCLUSIONS: Our results demonstrate genetic maternal effect contributes to the risk of CTD. Failure to account for maternal effect results in an incomplete understanding of the genetic risk architecture of CTD, as the risk for CTD is impacted by maternal effect which is above and beyond the risk from transmitted genetic effect.
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| 3. |
- Mahjani, Behrang, et al.
(författare)
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Maternal Effects as Causes of Risk for Obsessive-Compulsive Disorder
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 87:12, s. 1045-1051
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: While genetic variation has a known impact on the risk for obsessive-compulsive disorder (OCD), there is also evidence that there are maternal components to this risk. Here, we partitioned sources of variation, including direct genetic and maternal effects, on risk for OCD.METHODS: The study population consisted of 822,843 individuals from the Swedish Medical Birth Register, born in Sweden between January 1, 1982, and December 31, 1990, and followed for a diagnosis of OCD through December 31, 2013. Diagnostic information about OCD was obtained using the Swedish National Patient Register.RESULTS: A total of 7184 individuals in the birth cohort (0.87%) were diagnosed with OCD. After exploring various generalized linear mixed models to fit the diagnostic data, genetic maternal effects accounted for 7.6% (95% credible interval: 6.9%-8.3%) of the total variance in risk for OCD for the best model, and direct additive genetics accounted for 35% (95% credible interval: 32.3%-36.9%). These findings were robust under alternative models.CONCLUSIONS: Our results establish genetic maternal effects as influencing risk for OCD in offspring. We also show that additive genetic effects in OCD are overestimated when maternal effects are not modeled.
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| 4. |
- Sandin, Sven, et al.
(författare)
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The familial risk of autism
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - Chicago, USA : American Medical Association. - 0098-7484 .- 1538-3598. ; 311:17, s. 1770-1777
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental factors remains unresolved.Objective: To provide estimates of familial aggregation and heritability of ASD.Design, setting and participants: A population-based cohort including 2,049,973 Swedish children born 1982 through 2006. We identified 37,570 twin pairs, 2,642,064 full sibling pairs, 432,281 maternal and 445,531 paternal half sibling pairs, and 5,799,875 cousin pairs. Diagnoses of ASD to December 31, 2009 were ascertained.Main outcomes and measures: The relative recurrence risk (RRR) measures familial aggregation of disease. The RRR is the relative risk of autism in a participant with a sibling or cousin who has the diagnosis (exposed) compared with the risk in a participant with no diagnosed family member (unexposed). We calculated RRR for both ASD and autistic disorder adjusting for age, birth year, sex, parental psychiatric history, and parental age. We estimated how much of the probability of developing ASD can be related to genetic (additive and dominant) and environmental (shared and nonshared) factors.Results: In the sample, 14,516 children were diagnosed with ASD, of whom 5689 had autistic disorder. The RRR and rate per 100,000 person-years for ASD among monozygotic twins was estimated to be 153.0 (95% CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed ); for dizygotic twins, 8.2 (95% CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full siblings, 10.3 (95% CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half siblings, 3.3 (95% CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half siblings, 2.9 (95% CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0 (95% CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for autistic disorder but of slightly higher magnitude.We found support for a disease etiology including only additive genetic and nonshared environmental effects. The ASD heritability was estimated to be 0.50 (95% CI, 0.45-0.56) and the autistic disorder heritability was estimated to 0.54 (95% CI, 0.44-0.64).Conclusions and relevance: Among children born in Sweden, the individual risk of ASD and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and autistic disorder were estimated to be approximately 50%. These findings may inform the counseling of families with affected children.
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| 5. |
- Silverman, Michael E., et al.
(författare)
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The risk factors for postpartum depression : A population-based study
- 2017
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Ingår i: Depression and anxiety (Print). - Hoboken, USA : John Wiley & Sons. - 1091-4269 .- 1520-6394. ; 34:2, s. 178-187
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postpartum depression (PPD) can result in negative personal and child developmental outcomes. Only a few large population-based studies of PPD have used clinical diagnoses of depression and no study has examined how a maternal depression history interacts with known risk factors. The objective of this study was to examine the impact of a depression history on PPD and pre- and perinatal risk factors.Methods: A nationwide prospective cohort study of all women with live singleton births in Sweden from 1997 through 2008 was conducted. Relative risk (RR) of clinical depression within the first year postpartum and two-sided 95% confidence intervals were estimated.Results: The RR of PPD in women with a history of depression was estimated at 21.03 (confidence interval: 19.72-22.42), compared to those without. Among all women, PPD risk increased with advanced age (1.25 (1.13-1.37)) and gestational diabetes (1.70 (1.36-2.13)). Among women with a history of depression, pregestational diabetes (1.49 (1.01-2.21)) and mild preterm delivery also increased risk (1.20 (1.06-1.36)). Among women with no depression history, young age (2.14 (1.79-2.57)), undergoing instrument-assisted (1.23 (1.09-1.38)) or cesarean (1.64(1.07-2.50)) delivery, and moderate preterm delivery increased risk (1.36 (1.05-1.75)). Rates of PPD decreased considerably after the first postpartum month (RR = 0.27).Conclusions: In the largest population-based study to date, the risk of PPD was more than 20 times higher for women with a depression history, compared to women without. Gestational diabetes was independently associated with a modestly increased PPD risk. Maternal depression history also had a modifying effect on pre- and perinatal PPD risk factors.
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| 6. |
- Stålberg, Gabriella, et al.
(författare)
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Video-based assessment of interpersonal problem solving skills in patients with schizophrenia, their siblings and non-psychiatric controls
- 2008
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 49:1, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyze social functioning in patients with schizophrenia and their biological relatives with a Swedish version of the video-based vignette test Assessment of Interpersonal Problem Solving Skills (AIPSS). In a new video production with simulated "real life" situations we tested the ability to receive, process and send social information in 25 individuals with a DSM-IV diagnosis of schizophrenia, 20 siblings to patients with schizophrenia and 25 randomly selected non-psychiatric controls. The test proved to have good validity and interrater reliability. After controlling for positive or negative symptoms, patients had poor performance especially in acting out solutions leading to effective problem solving. Siblings generally did not differ from controls, but showed some deficiencies in non-verbal language. To conclude, AIPSS is appropriate for use in a Swedish-speaking context and might be useful in research on vulnerability indicators and in assessment of treatment interventions.
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| 7. |
- Svensson, Anna C., et al.
(författare)
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Familial aggregation of schizophrenia : The moderating effect of age at onset, parental immigration, paternal age and season of birth
- 2012
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 40:1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- Aims: An abundance of evidence has firmly established the familial aggregation of schizophrenia. The aim of this study was to examine how age at onset, parental characteristics and season of birth modify the familiality in schizophrenia. Methods: A population-based cohort was created by linking the Swedish Multi-Generation and Hospital Discharge Registers. Among 5,075,998 full siblings born between 1932 through to 1990, 16,346 cases of schizophrenia were identified. Familial aggregation was measured by the sibling recurrence-risk ratio, defined as the risk of schizophrenia among full siblings of schizophrenia patients compared with the risk among siblings of unaffected people. Results: We found a statistically significantly lower recurrence-risk ratio in siblings of later onset cases (7.2; 95% confidence interval (95% CI) 6.7-7.9) than of early onset cases (10.8; 95% CI 9.4-12.2). A lower recurrence-risk ratio was observed among offspring to fathers above 40 years (6.3; 95% CI 5.3-7.3) as compared with offspring of younger fathers (8.6; 95% CI 8.0-9.3). Further, among offspring to parents born outside Sweden the recurrence-risk ratio was statistically significantly lower (maternal immigrants 4.8; 95% CI 4.0-5.7, paternal immigrants 5.7; 95% CI 4.6-6.9) than among offspring to parents born in Sweden. Conclusions: The familial aggregation of schizophrenia was reduced by higher age at onset, advancing paternal age and immigrant status of parents.
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| 8. |
- Svensson, Anna C., et al.
(författare)
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Fertility of first-degree relatives of patients with schizophrenia : A three generation perspective
- 2007
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 91:1-3, s. 238-245
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Tidskriftsartikel (refereegranskat)abstract
- We explored the fertility in three generations; fertility of parents, siblings and offspring to patients with schizophrenia, to test the hypothesis that the decreased reproductive rate in the patients is compensated by an increased rate in their first-degree relatives. A population-based national database was created by linking the Swedish Multi-Generation and Hospital Discharge Registers. To maximize follow-up time for schizophrenia and reproductive history, three birth cohorts were selected: parental generation, born 1918–1927 (n=274464); affected generation, born 1932–1941 (n=108502) and offspring to affected generation, born 1951–1960 (n=103105). Ratios of estimated mean number of offspring were measured (fertility ratios), comparing the study subjects to the general population. The fertility among males with schizophrenia was decreased by over 70% (fertility ratiopatients/population=0.29, 95% CI 0.25–0.35), whereas female patients had less than half as many offspring as the general female population (fertility ratiopatients/population=0.48, 95% CI 0.42–0.55). When accounting for selection bias of larger families, no statistically significant difference was found among parents of patients with and without a diagnosis of schizophrenia. Further, the fertility among siblings of schizophrenic patients did not differ from the general population. A reduction in fertility was found among offspring to patients with schizophrenia, male offspring had 12% fewer offspring (fertility ratiooffspring/population=0.88, 95%CI 0.77–1.01), while female offspring had 6% fewer offspring (fertility ratiooffspring/population=0.94, 95% CI 0.84–1.05). In conclusion, we found reduced fertility in patients with schizophrenia and among their offspring that was not compensated by higher parental or sibling fertility.
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| 9. |
- Svensson, C, et al.
(författare)
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Maternal Effects for Preterm Birth : A Genetic Epidemiologic Study of 630,000 Families
- 2009
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 170:11, s. 1365-1372
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Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken to disentangle the maternal genetic from the fetal genetic effects for preterm birth and to study the possibility of these effects being explained by known risk factors. By cross-linking of the population-based Swedish Multigeneration and Medical Birth registers, 989,027 births between 1992 and 2004 were identified. Alternating logistic regression was applied to model the familial clustering with pairwise odds ratios (PORs), and covariates were included to evaluate if the familial aggregation was explained by exposure to shared risk factors. Generalized linear mixed models were used to estimate the contribution of genetic and environmental effects. Sisters of women who had a preterm delivery had themselves an increased odds of having a preterm delivery (POR = 1.8, 95% confidence interval: 1.5, 2.1), while there was no corresponding increase in odds in families joined by brothers (POR = 1.1, 95% confidence interval: 0.9, 1.4). Twenty-five percent of the variation in preterm birth was explained by maternal genetic factors, whereas fetal genetic factors only marginally influenced the variation in liability. The increased odds ratio between offspring of sisters was independent of maternal risk factors for preterm birth, suggesting that the relative importance of maternal effects is not explained by these well-known risk factors.
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| 10. |
- Tiikkaja, Sanna, et al.
(författare)
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Psychiatric disorder and work life : A longitudinal study of intra-generational social mobility
- 2016
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Ingår i: International Journal of Social Psychiatry. - : SAGE Publications. - 0020-7640 .- 1741-2854. ; 62:2, s. 156-166
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intra-generational social mobility, which describes the mobility within an individual’s own working life, is seldom studied among employees with psychiatric disorders (EPD). There is need of knowledge of the intra-generational mobility patterns, in a broader perspective, among EPD.Aims: To investigate intra-generational social mobility in employed individuals diagnosed with affective disorder, personality disorder, schizophrenia and drug dependence in a national Swedish cohort.Method: We identified a national sample of employed Swedish adults born in 1939–1949 (N = 876, 738), and among them individuals with a first-time hospital admission for affective psychosis, neurosis and personality disorder, alcoholism, drug dependence or schizophrenia in 1964–1980 (N = 18, 998). Employed individuals without hospital admission for such diagnoses were utilised as a comparison group (N = 866, 442). Intra-individual social class changes between 1980 and 1990 among EPD and the comparison group were described through summary statistics and graphs.Results: EPD more often held Low manual occupations at baseline in 1980 than the comparison group (44% vs. 28%), although parental social class was similar. In 1990, 19% of EPD and 4% of the comparison group had lost contact with the labour market. Social stability was less common among EPD (49 %) than in the comparison group (67%). Mobility out of the labour force increased and social stability decreased by number of inpatient admissions. Employees diagnosed with affective psychosis or neurosis and personality disorder fared better in the labour market than employees with schizophrenia.Conclusion: Employees suffering from psychiatric disorder do not maintain their social class or remain in the labour force to the same extent as individuals without those problems, irrespective of their parental class. Our results support the social drift hypothesis that individuals with poor psychiatric health move downward in the social hierarchy.
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