| 1. |
- Gong, Tong, et al.
(författare)
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The genetic architecture of dog ownership : large-scale genome-wide association study in 97,552 European-ancestry individuals.
- 2024
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Ingår i: G3. - 2160-1836.
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Tidskriftsartikel (refereegranskat)abstract
- Dog ownership has been associated with several complex traits and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through meta-analysis of 31,566 Swedish twins in five discovery cohorts and additional 65,986 European-ancestry individuals in three replication cohorts from Sweden, Norway, and the UK. Association test with >7.4 million single-nucleotide polymorphisms were meta-analyzed using a fixed effect model after controlling for population structure and relatedness. We identified two suggestive loci using discovery cohorts, which did not reach genome-wide significance after meta-analysis with replication cohorts. Single-nucleotide polymorphisms-based heritability of dog ownership using linkage disequilibrium score regression was estimated at 0.123 (CI 0.038-0.207) using the discovery cohorts and 0.018 (CI -0.002, 0.039) when adding in replication cohorts. Negative genetic correlation with complex traits including type 2 diabetes, depression, neuroticism and asthma was only found using discovery summary data. Furthermore, we did not identify any genes/gene-sets reaching even suggestive level of significance. This genome-wide association study does not, by itself, provide clear evidence on common genetic variants that influence the dog ownership among European-ancestry individuals.
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| 2. |
- Guintivano, Jerry, et al.
(författare)
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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
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| 3. |
- Javaras, Kristin N., et al.
(författare)
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Sex- and age-specific incidence of healthcare-register-recorded eating disorders in the complete swedish 1979-2001 birth cohort
- 2015
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Ingår i: International Journal of Eating Disorders. - : Wiley-Blackwell. - 0276-3478 .- 1098-108X. ; 48:8, s. 1070-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the sex- and age-specific incidence of healthcare-register-recorded anorexia nervosa (AN) and other eating disorders (OED) in a complete birth cohort, and assess whether incidence varies by diagnostic period and (sub-) birth cohort.METHOD: We used the actuarial method and Poisson models to examine the incidence of AN and OED from 1987 to 2009 (when individuals were 8-30 years old) for a cohort of 2.3 million individuals (48.7% female) born from 1979 to 2001 in Sweden, identified using Swedish registers.RESULTS: For both sexes, incidences of AN and OED increased considerably for diagnostic periods after 2000, but differed little by birth cohort. In 2009, AN incidence in the peak age category was 205.9 cases/100,000 persons (95% CI: 178.2, 233.5) for females (14-15 years), versus 12.8 cases/100,000 (95% CI: 5.6, 20.1) for males (12-13 years). OED incidence in the peak age category was 372.1 cases/100,000 (95% CI: 336.4, 407.9) for females (16-17 years), versus 22.2 cases/100,000 (95% CI: 13.3, 31.1) for males (14-15 years).DISCUSSION: Our finding of an increase in healthcare-register-recorded eating disorders for diagnostic periods after 2000 likely reflects improved detection and expanded register coverage in Sweden. The peak of eating disorder incidence in adolescence, which began unexpectedly early for AN in males, suggests the importance of vigilance for signs of AN in young boys and early primary prevention efforts. Waiting until later could miss critical windows for intervention that could prevent disorders from taking root.
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| 4. |
- Schaumberg, Katherine, et al.
(författare)
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The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders
- 2017
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Ingår i: European eating disorders review. - : WILEY. - 1072-4133 .- 1099-0968. ; 25:6, s. 432-450
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Forskningsöversikt (refereegranskat)abstract
- ObjectiveIn 2015, the Academy for Eating Disorders collaborated with international patient, advocacy, and parent organizations to craft the Nine Truths About Eating Disorders'. This document has been translated into over 30 languages and has been distributed globally to replace outdated and erroneous stereotypes about eating disorders with factual information. In this paper, we review the state of the science supporting the Nine Truths'. MethodsThe literature supporting each of the Nine Truths' was reviewed, summarized and richly annotated. ResultsMost of the Nine Truths' arise from well-established foundations in the scientific literature. Additional evidence is required to further substantiate some of the assertions in the document. Future investigations are needed in all areas to deepen our understanding of eating disorders, their causes and their treatments. ConclusionsThe Nine Truths About Eating Disorders' is a guiding document to accelerate global dissemination of accurate and evidence-informed information about eating disorders. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
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| 5. |
- Song, Jie, et al.
(författare)
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THE IMPACT OF EDUCATIONAL ATTAINMENT, INTELLIGENCE AND INTELLECTUAL DISABILITY ON SCHIZOPHRENIA : A SWEDISH POPULATION-BASED REGISTER AND GENETIC STUDY
- 2021
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 51, s. e137-e138
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Schizophrenia (SCZ) is highly heterogenous and no subtypes have been established to have good clinical utility in characterizing treatment response or longitudinal course. Cognitive impairment is one of the core clinical features of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive ability is complex, with limited studies of comprehensive epidemiological and genomic evidence.Methods: To comprehensively examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two samples from Sweden: a national cohort (13 738 SCZ cases and 3 677 172 controls) and a subsample with comprehensive genetic data (4 992 cases and 6 009 controls).Results: Population-based analyses showed worse cognition as risk factors for SCZ, and the pedigree genetic correlations between them were comparable with estimations from common genetic variants. In the genotyped subsample, premorbid cognitive ability and EDU were associated positively with their genetic risk score (GRS) and negatively with total number of rare exonic variants. The total size of copy number variants (CNV) deletions was associated with premorbid cognitive ability in controls. Finally, by applying an empirical clustering method, we dissect SCZ cases into four subgroups, defined by sex and ID. In particular, female cases with ID showed higher suicide-related events in the population cohort, and male-ID cases in genetic subsample had higher CNV and rare exonic burdens.Discussion: In conclusion, we found extensive evidence of a robust relation between cognitive ability and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.
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| 6. |
- Sullivan, Patrick F., et al.
(författare)
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Leveraging base-pair mammalian constraint to understand genetic variation and human disease
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643, s. 367-
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.
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| 7. |
- Yao, Shuyang, et al.
(författare)
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Criminal offending as part of an alternative reproductive strategy : investigating evolutionary hypotheses using Swedish total population data
- 2014
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Ingår i: Evolution and human behavior. - : Elsevier BV. - 1090-5138 .- 1879-0607. ; 35:6, s. 481-488
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Tidskriftsartikel (refereegranskat)abstract
- Criminality is highly costly to victims and their relatives, but often also to offenders. From an evolutionary viewpoint, criminal behavior may persist despite adverse consequences by providing offenders with fitness benefits as part of a successful alternative mating strategy. Specifically, criminal behavior may have evolved as a reproductive strategy based on low parental investment reflected in low commitment in reproductive relationships. We linked data from nationwide total population registers in Sweden to test if criminality is associated with reproductive success. Further, we used several different measures related to monogamy to determine the relation between criminal behavior and alternative mating tactics. Convicted criminal offenders had more children than individuals never convicted of a criminal offense. Criminal offenders also had more reproductive partners, were less often married, more likely to get remarried if ever married, and had more often contracted a sexually transmitted disease than non-offenders. Importantly, the increased reproductive success of criminals was explained by a fertility increase from having children with several different partners. We conclude that criminality appears to be adaptive in a contemporary industrialized country, and that this association can be explained by antisocial behavior being part of an adaptive alternative reproductive strategy.
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| 8. |
- Yao, Shuyang, et al.
(författare)
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Familial liability for eating disorders and suicide attempts : evidence from a population registry in Sweden
- 2017
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Ingår i: JAMA Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2168-622X .- 2168-6238.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Suicide attempts are common in individuals with eating disorders. More precise understanding of the mechanisms underlying their co-occurrence is needed. Objective: To examine the association between eating disorders and suicide attempts and whether familial risk factors contribute to the association. Design: A cohort design following a Swedish birth cohort 1979-2001 from age 6 until 31/12/2009. Setting: Information was acquired from Swedish national registers. Participants: Individuals born 1979-2001 and living in Sweden before age 6 (N= 2,268,786) were eligible for the study. Each individual was linked to his/her biological full-siblings, maternal half-siblings, paternal half-siblings, full-cousins, and half-cousins. Eating disorders were captured by three variables: any eating disorder, anorexia nervosa (AN), and bulimia nervosa (BN), identified by any lifetime diagnoses recorded in the registers. Suicide attempts were defined as any suicide attempts, including death by suicide, recorded in the registers. We examined the association between eating disorders and death by suicide separately, but were underpowered to explore familial liability for this association. Results: Individuals with any eating disorder had increased risk of suicide attempts (OR=5.28, 95%CI [5.04, 5.54]) and death by suicide (OR=5.39, 95%CI [4.00, 7.25]). The risks attenuated but remained significant after adjusting for comorbid major depressive disorder, anxiety disorders, and substance use disorder. Similar results were found for AN and BN, except that adjusted OR of death by suicide in BN became insignificant, possibly due to insufficient power. Individuals (index) who had a full-sibling with any eating disorder had increased risk of suicide attempts (OR=1.41, 95%CI [1.29, 1.53]). The risk attenuated for any eating disorder in more distant relatives (maternal half-siblings, OR=1.10, 95%CI [0.90, 1.34]; paternal half-siblings, OR=1.21, 95%CI [0.98, 1.49]; full-cousins, OR=1.11, 95%CI [1.06, 1.18]; half-cousins, OR=0.90, 95%CI [0.78, 1.03]). This familial pattern remained stable after adjusting for the index individuals’ eating disorders. Similar patterns were found for AN and BN. Conclusions and Relevance: Our results suggest increased risk of suicide attempts in individuals with lifetime eating disorders and their relatives. The pattern of familial co-aggregation suggests familial liability for the association between eating disorders and suicide. Psychiatric comorbidities partially explain this association, suggesting particularly high-risk presentations.
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| 9. |
- Yao, Shuyang, et al.
(författare)
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Genetic and environmental contributions to diagnostic fluctuation in anorexia nervosa and bulimia nervosa
- 2021
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 51:1, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anorexia nervosa and bulimia nervosa are two severe eating disorders associated with high premature mortality, suicidal risk and serious medical complications. Transition between anorexia nervosa and bulimia nervosa over the illness course and familial co-aggregation of the two eating disorders imply aetiological overlap. However, genetic and environmental liabilities to the overlap are poorly understood. Quantitative genetic research using clinical diagnosis is needed.METHODS: We acquired a clinical diagnosis of anorexia nervosa (prevalence = 0.90%) and bulimia nervosa (prevalence = 0.48%) in a large population-based sample (N = 782 938) of randomly selected full-sisters and maternal half-sisters born in Sweden between 1970 and 2005. Structural equation modelling was applied to quantify heritability of clinically diagnosed anorexia nervosa and bulimia nervosa and the contributions of genetic and environmental effects on their overlap.RESULTS: The heritability of clinically diagnosed anorexia nervosa and bulimia nervosa was estimated at 43% [95% confidence interval (CI) (36-50%)] and 41% (31-52%), respectively, in the study population, with the remaining variance explained by variance in unique environmental effects. We found statistically significant genetic [0.66, 95% CI (0.49-0.82)] and unique environmental correlations [0.55 (0.43-0.66)] between the two clinically diagnosed eating disorders; and their overlap was about equally explained by genetic and unique environmental effects [co-heritability 47% (35-58%)].CONCLUSIONS: Our study supports shared mechanisms for anorexia nervosa and bulimia nervosa and extends the literature from self-reported behavioural measures to clinical diagnosis. The findings encourage future molecular genetic research on both eating disorders and emphasize clinical vigilance for symptom fluctuation between them.
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| 10. |
- Yao, Shuyang
(författare)
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Genetic and environmental influences on eating disorders and associated adversities and comorbidities
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Eating disorders (EDs), including anorexia nervosa (AN) and bulimia nervosa (BN), are severe psychiatric disorders. Adversities (including suicide) and comorbidities have been illustrated in clinical observations with varying sample sizes, but evidence from large epidemiological research is still lacking. Further, the mechanisms underlying the observed associations remain largely unclear. Taking advantage of the unique Swedish national registries, this thesis aims to examine the associations between EDs and between EDs and potential adversities and comorbidities at population level and deepen the understanding of the mechanisms underlying these associations using genetically informative study designs. Study I applied quantitative genetic modeling to estimate genetic and environmental effects on AN and BN and their overlap. This study used registry data in siblings and half-siblings, which significantly increased the sample size and extended the literature from self-reported behavioral measures to clinical diagnosis. Consistent with twin studies, moderate heritability was found for both AN and BN. Furthermore, moderate genetic and environmental correlations were found between clinically diagnosed AN and BN, suggesting partially overlapped etiologies between the two EDs in the general population. Study II focused on the associations between EDs and suicide attempts and death by suicide. At population level, significantly increased risks of both suicide attempts and death by suicide were found in individuals with EDs (over 5 times the risk) compared to in individuals without EDs. Individuals with full-sibling or cousins with EDs were also at increased risks of suicide attempts. The familial co-aggregation pattern suggested that EDs and suicide attempts might share familial liabilities, which could include genetic and/or environmental risk factors shared by family members. Study III assessed the risks of committing theft and other crimes in EDs in a nationwide female cohort. Firstly, significantly higher risks of both theft and other crimes were found in exposed females (i.e., had been diagnosed with AN or BN) than in unexposed females; theft was more common than other crimes altogether in exposed groups; and both the absolute and relative risks were higher in BN than in AN. Next, sibling comparison design, where the risks were compared between differentially exposed full-sisters, was applied to account for potential confounding effects of familial factors shared between sisters. The relative risk of theft decreased but remained statistically significant in BN and did not decrease in AN. The finding suggests that familial confounders (e.g., genetic and/or familial environmental confounders) were likely to explain part of the association between BN and theft but not the association between AN and theft, potentially reflecting different etiologies of the two EDs. Study IV examined the genetic associations between EDs and attention-deficit/hyperactivity disorder (ADHD) using multiple approaches, namely assessing familial co-aggregation, quantitative genetic modeling, and analysis of polygenic risk scores (PRS, a measure of genetic risk of a disorder). 1) Increased risks of being diagnosed with AN and non-AN EDs (including BN) were found in individuals diagnosed with ADHD and their full- and maternal half-siblings and cousins, compared to individuals without ADHD and their relatives, suggesting familial liabilities shared between ADHD and the EDs. 2) Moderate genetic correlations were found between non-AN EDs and ADHD and between BN and ADHD, and mild genetic correlation was found between AN and ADHD. 3) ADHD PRS significantly predicted ED symptoms including drive for thinness and body dissatisfaction in a large genotyped population sample, indicating that the polygenic risk of ADHD influenced some ED symptoms. The findings of the three approaches converged and together illustrated significant genetic correlations between EDs, especially non-AN EDs, and ADHD at both diagnostic and symptomatic levels. Both ADHD and theft behaviors (in Study III) might reflect multi-impulsive forms of EDs which, as suggested by previous studies, may be associated with relatively poorer treatment response. Taken together, this thesis highlighted the seriousness of EDs by revealing their associations with adversities (suicide and crime) and comorbidity (ADHD) at population level. Further, it revealed the genetic and/or environmental influences on these associations and the associations among EDs. The findings suggest that EDs are correlated yet different disorders and provide insights on the etiologies underlying these important associations, encouraging future research to identify specific risk factors that target the shared etiologies. Clinical implications include the identification of subgroups in individuals with EDs who display high impulsivity and high risk of suicide as well as vigilance of forensic issues that could complicate treatment and recovery. The findings also highlighted increased risks of EDs, adversities, and comorbidity in family members of individuals with EDs, calling for clinical attention to the psychological robustness of the relatives especially when they serve as the caregivers of ED patients and are expected to engage intensively in treatment.
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