Common Genetic Variation And Age at Onset Of Anorexia Nervosa

Background Genetics and biology may influence the age at onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to AN age at onset and to investigate the genetic associations between age at 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 9,335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age at 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 (SNP-h2) were 0.01-0.04 for age at 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 at onset and early-onset AN estimated from independent GWASs significantly predicted age at 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 at onset and implicate biological pathways regulating menarche and reproduction.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Regression of corneal topography changes following reading

Purpose Reading causes the corneal shape to change. We studied the time course of recovery of corneal topography changes following various periods of reading. Methods Six young subjects with normal ocular health were recruited for the study. Experiments were conducted early in the morning on four separate days and the subjects were instructed to perform no significant reading tasks prior to the experiment. At each session, baseline corneal shape was measured by taking six videokeratographs and averaging the maps. The subject then read a novel for 10, 30, 60 or 120 mins. Following the reading task, videokeratoscopy was measured at 17 pre–defined time intervals up to 3 hrs following the reading task. Six videokeratographs were acquired at each of these time points during the recovery phase and later averaged. During the recovery period the subjects were not permitted to perform any intensive reading or near work. Analysis took the form of comparison of the corneal topography pre–reading versus post–reading during the recovery phase. Results All six subjects showed statistically significant changes in the cornea immediately following all four reading conditions (10 to 120 mins). In the corneal region corrsponding to the position of the upper lid margin, the group average maximum change in local refractive power was 0.94 D (+/–0.44) for the 120 min reading condition, 0.64 D (+/–0.31) for the 60 min condition, 0.60 D (+/–0.28) for the 30 min condition and 0.44 D (+/–0.42) for the 10 min reading condition. A one–way repeated measures ANOVA showed that the regression of corneal power over time was highly significant for all conditions (p=0.001). Plotting the regression of corneal power following reading showed a rapid recovery of shape following all 4 reading conditions during the initial 10 mins, with a subsequent slow recovery phase. As a generalization of the regression trends, we found that the topography was almost completely recovered to pre–reading shape after as many minutes as the subject had previously been reading. For example, 120 mins of reading required approximately 120 mins for full corneal shape recovery. Conclusions Corneal topography and optics change following reading and the magnitude of the changes are related to the length of time spent reading. The regression of these changes have an initial rapid phase of approximately 10 mins followed by a slower recovery phase

Dynamics of Ocular Surface Topography

PURPOSE: To investigate fluctuations in the ocular surface, we used high-speed videokeratoscopy (50 Hz) to measure the dynamics of the ocular surface topography. METHODS: Ocular surface height difference maps were computed to illustrate the changes in the tear film in the inter-blink interval. Topography data were used to derive the ocular surface wavefront aberrations up to the fourth radial order of the Zernike polynomial expansion. We examined the ocular surface dynamics and temporal changes in the ocular surface wavefront aberrations in the inter-blink interval. RESULTS: During the first 0.5 s following a blink, the ocular surface height at the upper edge of the topography map increased by about 2 mum. Temporal changes occurred for some ocular surface wavefront aberrations and appeared to be related to changes in the distribution of tear film. CONCLUSION: In the clinical measurement of ocular surface topography using videokeratoscopy or optics of the eye using wavefront sensors, care should be taken to avoid the initial tear film build-up phase following a blink to achieve more consistent results

Comparison of metabolic profiles of acutely ill and short-term weight recovered patients with anorexia nervosa reveals alterations of 33 out of 163 metabolites

Starvation represents an extreme physiological state and entails numerous endocrine and metabolic adaptations. The large-scale application of metabolomics to patients with acute anorexia nervosa (AN) should lead to the identification of state markers characteristic of starvation in general and of the starvation specifically associated with this eating disorder. Novel metabolomics technology has not yet been applied to this disorder. Using a targeted metabolomics approach, we analysed 163 metabolite concentrations in 29 patients with AN in the acute stage of starvation (T0) and after short-term weight recovery (T1). Of the 163 metabolites of the respective kit, 112 metabolites were quantified within restrictive quality control limits. We hypothesized that concentrations are different in patients in the acute stage of starvation (T0) and after weight gain (T1). Furthermore, we compared all 112 metabolite concentrations of patients at the two time points (T0, T1) with those of 16 age and gender matched healthy controls. Thirty-three of the metabolite serum levels were found significantly different between T0 and T1. At the acute stage of starvation (T0) serum concentrations of 90 metabolites differed significantly from those of healthy controls. Concentrations of controls mostly differed even more strongly from those of AN patients after short-term weight recovery than at the acute stage of starvation. We conclude that AN entails profound and longer lasting alterations of a large number of serum metabolites. Further studies are warranted to distinguish between state and trait related alterations and to establish diagnostic sensitivity and specificity of the thus altered metabolites