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- Munn-Chernoff, M. A., et al.
(author)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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In: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Journal article (peer-reviewed)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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- Bryois, J., et al.
(author)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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- Watson, H. J., et al.
(author)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
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Journal article (peer-reviewed)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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- Qi, B. Y., et al.
(author)
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Differential genetic associations between dimensions of eating disorders and alcohol involvement in late adolescent twins
- 2023
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In: Alcohol: Clinical and Experimental Research. - 0145-6008 .- 2993-7175. ; 47:9, s. 1677-1689
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Journal article (peer-reviewed)abstract
- Background: Twin studies have demonstrated shared genetic and environmental effects between eating disorders and alcohol involvement in adults and middle adolescents. However, fewer studies have focused on late adolescents or investigated a wide range of eating disorder dimensions and alcohol involvement subscales in both sexes. We examined genetic and environmental correlations among three eating disorder dimensions and two alcohol involvement subscale scores in late adolescent twins using bivariate twin models.Methods: Participants were 3568 female and 2526 male same-sex twins aged 18 years old from the Child and Adolescent Twin Study in Sweden. The Eating Disorder Inventory-2 (EDI) assessed the drive for thinness, bulimia, and body dissatisfaction. Alcohol involvement was assessed with the Alcohol Use Disorder Identification Test consumption (AUDIT-C) and problem (AUDIT-P) subscales.Results: Only phenotypic and twin correlations in female twins met our threshold for twin modeling. The proportion of total variance for each trait accounted for by additive genetic factors ranged from 0.50 to 0.64 in female twins, with the rest explained by nonshared environmental factors and measurement error. Shared environmental factors played a minimal role in the variance of each trait. The strongest genetic correlation (r(a)) emerged between EDI bulimia and AUDIT-P (r(a) = 0.46, 95% confidence interval: 0.37, 0.55), indicating that the proportion of genetic variance of one trait that was shared with the other trait was 0.21. Nonshared environmental correlations between eating disorder dimensions and alcohol involvement ranged from 0.03 to 0.13.Conclusions: We observed distinct patterns of genetic and environmental effects for co-occurring eating disorder dimensions and alcohol involvement in female vs. male twins, supporting sex-specific treatment strategies for late adolescents with comorbid eating disorders and alcohol use disorder. Our findings emphasize the importance of assessing family history of multiple eating disorder dimensions while treating late adolescents with problematic alcohol use, and vice versa, to improve detection and treatment.
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- Schaumberg, Katherine, et al.
(author)
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The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders
- 2017
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In: European eating disorders review. - : WILEY. - 1072-4133 .- 1099-0968. ; 25:6, s. 432-450
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Research review (peer-reviewed)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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- Javaras, Kristin N., et al.
(author)
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Shared Genetic Factors Contributing to the Overlap between Attention-Deficit/Hyperactivity Disorder Symptoms and Overweight/Obesity in Swedish Adolescent Girls and Boys
- 2022
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In: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 25:6, s. 226-233
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Journal article (peer-reviewed)abstract
- Attention-deficit/hyperactivity disorder (ADHD) and obesity are positively associated, with increasing evidence that they share genetic risk factors. Our aim was to examine whether these findings apply to both types of ADHD symptoms for female and male adolescents. We used data from 791 girl and 735 boy twins ages 16-17 years to examine sex-specific phenotypic correlations between the presence of ADHD symptoms and overweight/obese status. For correlations exceeding .20, we then fit bivariate twin models to estimate the genetic and environmental correlations between the presence of ADHD symptoms and overweight/obese status. ADHD symptoms and height/weight were parent- and self-reported, respectively. Phenotypic correlations were .30 (girls) and .08 (boys) for inattention and overweight/obese status and .23 (girls) and .14 (boys) for hyperactivity/impulsivity and overweight/obese status. In girls, both types of ADHD symptoms and overweight/obese status were highly heritable, with unique environmental effects comprising the remaining variance. Furthermore, shared genetic effects explained most of the phenotypic correlations in girls. Results suggest that the positive association of both types of ADHD symptoms with obesity may be stronger in girls than boys. Further, in girls, these associations may stem primarily from shared genetic factors.
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- Watson, Hunna J., et al.
(author)
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A Register-Based Case-Control Study of Prescription Medication Utilization in Binge-Eating Disorder
- 2016
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In: The primary care companion for CNS disorders. - Memphis, USA : Physicians Postgraduate Press, Inc.. - 2155-7780. ; 18:4
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Journal article (peer-reviewed)abstract
- Objective: Individuals with binge-eating disorder (BED) experience psychiatric and somatic comorbidities and obesity, but the nature and magnitude of prescription medication utilization is unclear. We investigated utilization using Swedish registry data and a case-control design.Methods: Cases were identified from Riksät and Stepwise longitudinal registers and were individuals diagnosed with BED per DSM-IV-TR criteria between July 1, 2006, and December 31, 2009, at eating disorder clinics (n = 238, 96% female, mean age = 22.8 years). For each case, 10 controls were matched on sex and year, month, and county of birth (n = 2,380). An index date was derived for each control, which was the date of diagnosis of BED in the corresponding case. The association between BED and prescription medication utilization was investigated before and within 12 months after diagnosis.Results: Before diagnosis, cases were significantly more likely than matched controls to have been prescribed nervous system (odds ratio = 6.4; 95% confidence limit = 4.7, 8.6), tumors and immune disorders (3.5; 1.3, 9.3), cardiovascular (2.2; 1.4, 3.5), digestion and metabolism (2.1; 1.5, 2.9), infectious diseases (1.9; 1.4, 2.6), skin (1.8; 1.3, 2.5), and respiratory system (1.3; 1.0, 1.8) medications. Cases also had higher odds of prescription use than controls across most categories within 12 months after diagnosis. Several associations were significant after accounting for lifetime psychiatric comorbidity and obesity.Conclusions: Individuals with BED had increased utilization of psychiatric and nonpsychiatric medications compared with matched controls. Findings confirm that the illness burden of BED extends to high medication utilization and underscore the importance of thorough medication reviews when treating individuals with BED.
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