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- 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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- Johnson, J. S., et al.
(författare)
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Mapping anorexia nervosa genes to clinical phenotypes
- 2023
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Ingår i: Psychological Medicine. - : Cambridge University Press (CUP). - 0033-2917 .- 1469-8978. ; 53:6, s. 2619-2633
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Tidskriftsartikel (refereegranskat)abstract
- Background Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes. Methods Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe (TM) Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations. Results Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex. Conclusions Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.
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- Geyer, Holly, et al.
(författare)
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Symptomatic Profiles of Patients With Polycythemia Vera : Implications of Inadequately Controlled Disease
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:2, s. 151-
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden.PATIENTS AND METHODS: Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly).RESULTS: The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S).CONCLUSION: The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.
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- Johansson, Therese, et al.
(författare)
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Polygenic association with severity and long-term outcome in eating disorder cases
- 2022
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- About 20% of individuals with anorexia nervosa (AN) remain chronically ill. Therefore, early identification of poor outcome could improve care. Genetic research has identified regions of the genome associated with AN. Patients with anorexia nervosa were identified via the Swedish eating disorder quality registers Stepwise and Riksat and invited to participate in the Anorexia Nervosa Genetics Initiative. First, we associated genetic information longitudinally with eating disorder severity indexed by scores on the Clinical Impairment Assessment (CIA) in 2843 patients with lifetime AN with or without diagnostic migration to other forms of eating disorders followed for up to 16 years (mean = 5.3 years). Second, we indexed the development of a severe and enduring eating disorder (SEED) by a high CIA score plus a follow-up time >= 5 years. We associated individual polygenic scores (PGSs) indexing polygenic liability for AN, schizophrenia, and body mass index (BMI) with severity and SEED. After multiple testing correction, only the BMI PGS when calculated with traditional clumping and p value thresholding was robustly associated with disorder severity (beta(PGS) = 1.30; 95% CI: 0.72, 1.88; p = 1.2 x 10(-5)) across all p value thresholds at which we generated the PGS. However, using the alternative PGS calculation method PRS-CS yielded inconsistent results for all PGS. The positive association stands in contrast to the negative genetic correlation between BMI and AN. Larger discovery GWASs to calculate PGS will increase power, and it is essential to increase sample sizes of the AN GWASs to generate clinically meaningful PGS as adjunct risk prediction variables. Nevertheless, this study provides the first evidence of potential clinical utility of PGSs for eating disorders.
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- Forsén Mantilla, Emma, et al.
(författare)
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Insidious: The relationship between patients and their eating disorders and its impact on ED symptoms, illness duration and self-image
- 2017
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Ingår i: EUROPEAN PSYCHIATRY. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 41, s. S552-S552
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients with eating disorders (EDs) often spontaneously talk about their disorder in terms of a symbolic other (a demon, a voice, a guardian). Further, externalizing exercises where patients are encouraged to separate their true self from their ED self are common in some treatment approaches. Yet, no previous quantitative study has investigated this phenomenon. We examined the patient-ED relationship (using the interpersonal structural analysis of social behavior methodology) and its implications for ED symptoms, illness duration and self-image. Participants were 16–25 year old female patients (N = 150) diagnosed with anorexia nervosa (N = 55), bulimia nervosa (N = 33) or eating disorder not otherwise specified (N = 62). Results suggested that patients had comprehensible and organized relationships with their EDs. EDs were primarily experienced as acting critical and controlling towards patients. Higher ED control was associated with more ED symptoms and longer illness duration, especially when coupled with patient submission. Patients reacting more negatively towards their EDs than their EDs were acting towards them had lower symptom levels and more positive self-images. Externalizing one's ED, relating to it like a symbolic other, seemed to make sense to patients and depending on its quality seemed to influence ED symptoms, illness duration and self-image. We put forward both clinical and theoretical implications based on the assumption that the patient-ED relationship may function in similar ways as real-life interpersonal relationships do.The authors have not supplied their declaration of competing interest.
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- Zhang, R. Y., et al.
(författare)
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Association of autism diagnosis and polygenic scores with eating disorder severity
- 2022
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Ingår i: European Eating Disorders Review. - : Wiley. - 1072-4133 .- 1099-0968. ; 30:5, s. 442-458
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Tidskriftsartikel (refereegranskat)abstract
- Among individuals with eating disorders (ED), those with co-occurring autism are often considered to have more severe presentations and poorer prognosis. However, previous findings have been contradictory and limited by small sample size and/or cross-sectional assessment of autistic traits. We examine the hypothesis that autism diagnosis and autism polygenic score (PGS) are associated with increased ED severity in a large ED cohort using a broad range of ED severity indicators. Our cohort included 3189 individuals (64 males) born 1977-2000 with current or previous anorexia nervosa who participated in the Anorexia Nervosa Genetics Initiative-Sweden (ANGI-SE) and for whom genotypes and linkage to national registers were available. We identified 134 (4.2%) individuals with registered autism diagnoses. Individuals with confirmed autism diagnosis had significantly more severe ED across three sets of severity indicators. Some of the largest effects were found for the proportion of individuals who attempted suicide and who received tube feeding (higher in autism), and for the time spent in inpatient care (longer in autism). Results for autism PGS were not statistically significant. Adapting ED treatment to the needs of individuals with co-occurring autism is an important research direction to improve treatment outcome in this group.
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