| 1. |
- Charney, Alexander W, et al.
(författare)
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Contribution of Rare Copy Number Variants toBipolar Disorder Risk Is Limited to Schizoaffective Cases.
- 2019
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Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 86:2, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p= .001), BD I (p= .0003), and BD II (p= .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p= .0007, PRS p= .004), and BD I without psychosis (CNV p= .0004, PRS p= 3.9× 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p= .005) but not CNV burden.CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
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| 2. |
- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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| 3. |
- Garcia-Argibay, Miguel, 1988-, et al.
(författare)
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The role of ADHD genetic risk in mid-to-late life somatic health conditions
- 2022
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence suggests that ADHD, an early onset neurodevelopmental disorder, is associated with poor somatic health in adulthood. However, the mechanisms underlying these associations are poorly understood. Here, we tested whether ADHD polygenic risk scores (PRS) are associated with mid-to-late life somatic health in a general population sample. Furthermore, we explored whether potential associations were moderated and mediated by life-course risk factors. We derived ADHD-PRS in 10,645 Swedish twins born between 1911 and 1958. Sixteen cardiometabolic, autoimmune/inflammatory, and neurological health conditions were evaluated using self-report (age range at measure 42-88 years) and clinical diagnoses defined by International Classification of Diseases codes in national registers. We estimated associations of ADHD-PRS with somatic outcomes using generalized estimating equations, and tested moderation and mediation of these associations by four life-course risk factors (education level, body mass index [BMI], tobacco use, alcohol misuse). Results showed that higher ADHD-PRS were associated with increased risk of seven somatic outcomes (heart failure, cerebro- and peripheral vascular disease, obesity, type 1 diabetes, rheumatoid arthritis, and migraine) with odds ratios ranging 1.07 to 1.20. We observed significant mediation effects by education, BMI, tobacco use, and alcohol misuse, primarily for associations of ADHD-PRS with cardiometabolic outcomes. No moderation effects survived multiple testing correction. Our findings suggests that higher ADHD genetic liability confers a modest risk increase for several somatic health problems in mid-to-late life, particularly in the cardiometabolic domain. These associations were observable in the general population, even in the absence of medical treatment for ADHD, and appear to be in part mediated by life-course risk factors.
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| 4. |
- Leone, Marica, et al.
(författare)
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Association of severe childhood infections with depression and intentional self-harm in adolescents and young adults
- 2022
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Ingår i: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 99, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- Early-life infections have been linked with subsequent depression and self-harm. Examination of specific groups of infections and the role of familial factors may elucidate this observed relationship. We addressed these considerations in our investigations of the association of severe childhood infections with the risks of depression and self-harm in adolescence and early-adulthood. This population-based cohort study included all individuals born in Sweden between 1982 and 1996, with follow-up through 2013 (N = 1,506,070). Severe childhood infections were identified using inpatient and outpatient diagnoses from birth through age 12. Any infection as well as specific groups of infections were investigated. We examined diagnoses of depression and self-harm within inpatient and outpatient care and death by self-harm between ages 13 and 31. Cox proportional hazards regression models were used to estimate absolute risks, hazard ratios (HRs), and 95% CIs. When adjusting for sex and birth year, individuals exposed to any childhood infection demonstrated increased absolute risk differences for both outcomes (2.42% [95% CI, 0.41%-4.43%] of being diagnosed with depression up until age 31, and 0.73% [-2.05%-3.51%] of self-harm up until age 31) and increased relative risks (HR, 1.22 [1.20-1.24] for depression and HR, 1.29 [1.25-1.32] for self-harm). When controlling for unmeasured factors shared between family members by comparing discordant siblings, no strong association persisted. Our findings show that childhood infections may not be involved in the etiology of later depression and self-harm, and highlight the importance of identifying these genetic and environmental familial risk factors, which may serve as targets for interventions.
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| 5. |
- Leone, Marica, et al.
(författare)
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Association of Youth Depression With Subsequent Somatic Diseases and Premature Death
- 2021
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:3, s. 302-310
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Early-onset depression has been linked to poor health outcomes. However, it is unclear the extent to which this disorder is associated with specific diseases and premature death and whether these associations remain after controlling for psychiatric comorbidity.Objective: To quantify the association of youth depression with subsequent diagnoses of numerous somatic diseases and mortality.Design, Setting, and Participants: A population-based cohort study was conducted using Swedish national registers containing data on all individuals born in Sweden between 1982 and 1996. A total of 1 487 964 participants were followed up from age 5 years through 2013 if no censoring occurred. Data analysis was performed from January 15, 2019, to August 10, 2020.Exposures: Youth depression was defined as having received at least 1 diagnosis of depression from inpatient or outpatient care between ages 5 and 19 years.Main Outcomes and Measures: This study examined 69 somatic conditions diagnosed after youth depression, as well as all-cause and cause-specific mortalities. Overall and sex-specific hazard ratios (HRs), together with 95% CIs, were estimated using Cox proportional hazards regression with attained age as underlying timescale and time-varying exposure, and adjusted for birth year and sex. All analyses were repeated controlling for psychiatric comorbidities. Absolute risk differences were calculated using standardization with Cox proportional hazards regression.Results: Of 1 487 964 individuals included in the analysis, 51.2% were male. A total of 37 185 patients (2.5%; 67.4% female) had an inpatient or outpatient contact for depression between ages 5 and 19 years (mean [SD] age at first recorded diagnosis of depression, 16.7 [2.1] years for males and 16.7 [1.8] years for females). Age at the end of follow-up ranged between 17 and 31 years. Individuals with youth depression had higher relative risks for 66 of the 69 somatic diagnoses. Strong associations were observed for certain injuries, especially self-harm in females (HR, 14.4; 95% CI, 13.8-15.1), sleep disorders (HR, 8.1; 95% CI, 7.6-8.7), viral hepatitis (HR, 6.1; 95% CI, 5.4-6.8), all-cause mortality (HR, 5.9; 95% CI, 5.3-6.6), and cause-specific mortalities, especially death by intentional self-harm (HR, 14.6; 95% CI, 12.6-16.9). Most associations were attenuated but persisted after adjusting for psychiatric comorbidity. The absolute risk difference of a specific disease within 12 years from the first diagnosis of depression during youth ranged from -0.2% (95% CI, -1.0% to 0.6%) for arthropathies among males to 23.9% (95% CI, 22.7%-25.0%) for the broader category of injuries among females.Conclusions and Relevance: In this Swedish population cohort study, patients with depression diagnosed during their youth appeared to have increased risks for many somatic diseases as well as for mortality, even after controlling for other psychiatric disorders. These findings suggest that several medical conditions should be considered when investigating youth depression.
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| 6. |
- Liu, Shengxin, et al.
(författare)
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Early-Onset Type 2 Diabetes and Mood, Anxiety, and Stress-Related Disorders: A Genetically Informative Register-Based Cohort Study.
- 2022
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:12, s. 2950-2956
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Tidskriftsartikel (refereegranskat)abstract
- To assess the association and familial coaggregation between early-onset type 2 diabetes (diagnosed before age 45 years) and mood, anxiety, and stress-related disorders and estimate the contribution of genetic and environmental factors to their co-occurrence.This population-based cohort study included individuals born in Sweden during 1968-1998, from whom pairs of full siblings, half-siblings, and cousins were identified. Information on diagnoses of early-onset type 2 diabetes and mood (including unipolar depression and bipolar disorder), anxiety, and stress-related disorders was obtained from the National Patient Register. Logistic and Cox regression models were used to assess the phenotypic association and familial coaggregation between type 2 diabetes and psychiatric disorders. Quantitative genetic modeling was conducted in full and maternal half-sibling pairs to estimate the relative contributions of genetic and environmental factors to the association.Among a total of 3,061,192 individuals, 7,896 (0.3%) were diagnosed with early-onset type 2 diabetes. These individuals had higher risks of any diagnosis (odds ratio [OR] 3.62 [95% CI 3.44, 3.80]) and specific diagnosis of unipolar depression (3.97 [3.75, 4.22]), bipolar disorder (4.17 [3.68, 4.73]), anxiety (3.76 [3.54, 3.99]), and stress-related disorders (3.35 [3.11, 3.61]). Relatives of individuals with early-onset type 2 diabetes also had higher overall risks of the examined psychiatric disorders (ORs 1.03-1.57). These associations are largely explained by genetic factors (51-78%), with the rest explained by nonshared environmental factors.Our findings highlight the burden of mood, anxiety, and stress-related disorders in early-onset type 2 diabetes and demonstrate that shared familial liability may contribute to their co-occurrence, suggesting that in the future research investigators should aim to identify shared risk factors and ultimately refine preventive and intervention strategies.
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| 7. |
- Martin, Cederlöf, 1980-, et al.
(författare)
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Acute intermittent porphyria : comorbidity and shared familial risks with schizophrenia and bipolar disorder in Sweden
- 2015
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Ingår i: British Journal of Psychiatry. - London, United Kingdom : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 207:6, s. 556-557
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Tidskriftsartikel (refereegranskat)abstract
- Acute intermittent porphyria (AIP) has been associated with schizophrenia in some studies, but prior research is limited by the absence of comparison populations. Here, we linked Swedish registers to examine the risk of schizophrenia and bipolar disorder in 717 individuals diagnosed with AIP and their first-degree relatives, compared with matched individuals without AIP and their first-degree relatives. Individuals with AIP had a fourfold increased risk of schizophrenia or bipolar disorder. Similarly, relatives of individuals with AIP had double the risk of schizophrenia or bipolar disorder, suggesting that these associations may be as a result of common genetic influences.
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| 8. |
- Martin, Cederlöf, 1980-, et al.
(författare)
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The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study.
- 2015
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Ingår i: Bipolar disorders. - Hoboken, USA : Wiley. - 1399-5618 .- 1398-5647. ; 17:3, s. 340-4
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Tidskriftsartikel (refereegranskat)abstract
- Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question.
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| 9. |
- Song, Jie, et al.
(författare)
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Bipolar disorder and its relation to major psychiatric disorders : a family-based study in the Swedish population
- 2015
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Ingår i: Bipolar Disorders. - Stockholm : Wiley-Blackwell. - 1398-5647 .- 1399-5618. ; 17:2, s. 184-193
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders.METHODS: A population-based cohort was created by linking several Swedish national registers. A total of 54,723 individuals with BPD were identified among 8,141,033 offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives and the co-occurrence of other psychiatric disorders in patients with BPD and their relatives were compared to those of matched-population controls. Structural equation modeling was used to estimate the heritability and tetrachoric correlation.RESULTS: The familial risks for relatives of BPD probands were 5.8-7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence risks for other psychiatric disorders were 9.7-22.9 in individuals with BPD and 1.7-2.8 in full siblings of BPD probands. Heritability for BPD was estimated at 58%. The correlations between BPD and other psychiatric disorders were considerable (0.37-0.62) and primarily due to genetic effects. The correlation with depression was the highest (0.62), and was 0.44 for schizophrenia.CONCLUSIONS: The high familial risks provide evidence that genetic factors play an important role in the etiology of BPD, and the shared genetic determinants suggest pleiotropic effects across different psychiatric disorders. Results also indicate that BPD is in both the mood and psychotic spectra, but possibly more closely related to mood disorders.
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| 10. |
- Song, Jie, et al.
(författare)
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Key subphenotypes of bipolar disorder are differentially associated with polygenic liabilities for bipolar disorder, schizophrenia, and major depressive disorder
- 2024
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Ingår i: MOLECULAR PSYCHIATRY. - 1359-4184 .- 1476-5578.
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577). Participants were assessed through interviews and medical records for inter-episode remission, psychotic features during mood episodes, global assessment of functioning (GAF, function and symptom burden dimensions), and comorbid anxiety disorders. Meta-analyses based on both cohorts showed that inter-episode remission and GAF-function were positively correlated with BD-PRS but negatively correlated with schizophrenia-PRS (SCZ-PRS) and MDD-PRS. Moreover, BD-PRS was negatively, and MDD-PRS positively, associated with the risk of comorbid anxiety disorders. Finally, SCZ-PRS was positively associated with psychotic symptoms during mood episodes. Assuming a higher PRS of certain psychiatric disorders in cases with a positive family history, we further tested the associations between subphenotypes in index BD people and occurrence of BD, schizophrenia, or MDD in their relatives using Swedish national registries. BD patients with a relative diagnosed with BD had: (1) higher GAF and lower risk of comorbid anxiety than those with a relative diagnosed with schizophrenia or MDD, (2) lower risk of psychotic symptoms than those with a relative diagnosed with schizophrenia. Our findings shed light on the genetic underpinnings of the heterogeneity in clinical manifestations and course of illness in BD, which ultimately provide insights for developing personalized approaches to the diagnosis and treatment.
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