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Contemporary views on the genetics of anorexia nervosa.

ABSTRACT: Anorexia nervosa (AN) is a serious mental illness characterized by severe dietary restriction that leads to high rates of morbidity, chronicity, and mortality. Unfortunately, effective treatment is lacking and few options are available. High rates of familial aggregation and significant heritability suggested that the complex etiology of AN is affected by both genetic and environmental factors. In this paper, we review studies that reported common and rare genetic variation that influence susceptibility of AN through candidate gene studies, genome-wide association studies, and sequencing-based studies. We also discuss gene expression, methylation, imaging genetics, and pharmacogenetics to demonstrate that these studies have collectively advanced our knowledge of how genetic variation contributes to AN susceptibility and clinical course. Lastly, we highlight the importance of gene by environment interactions (G×E) and share our enthusiasm for the use of nutritional genomic approaches to elucidate the interaction among nutrients, metabolic intermediates, and genetic variation in AN. A deeper understanding of how nutrition alters genome stability, how genetic variation influences uptake and metabolism of nutrients, and how response to food components affects disordered eating, will lead to personalized dietary interventions and effective nutraceutical and pharmacological treatments for AN.

SUBMITTER: Shih PA

PROVIDER: S-EPMC4801707 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Contemporary views on the genetics of anorexia nervosa.

Shih Pei-an Betty PA Woodside D Blake DB

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 20160220 4

Anorexia nervosa (AN) is a serious mental illness characterized by severe dietary restriction that leads to high rates of morbidity, chronicity, and mortality. Unfortunately, effective treatment is lacking and few options are available. High rates of familial aggregation and significant heritability suggested that the complex etiology of AN is affected by both genetic and environmental factors. In this paper, we review studies that reported common and rare genetic variation that influence suscep ...[more]

PMID: 26944296

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Project description:ObjectivesRecovery from anorexia nervosa (AN) is difficult to define, and efforts to establish recovery criteria have led to several versions being proposed. Using the perspectives of people with histories of AN and therapists working in the field, we sought to explore the face validity of Khalsa et al (2017) as one of the most recent examples of proposed systematic recovery criteria.DesignWe interviewed 11 health service users (SUs) with histories of AN who had previously received treatment alongside 8 eating disorder therapists (EDTs), exploring their views on the proposed AN recovery criteria.MethodsData from verbal and written interviews were analysed thematically. Separate thematic analyses of SU and EDT interviews highlighted where concerns converged and diverged across participants.ResultsBoth groups saw some merits of having universally recognized recovery criteria, and the multidimensional approach was welcomed, but EDTs were uncomfortable with considering their use in therapy and SUs felt key components were missing around emotional coping and life quality. SUs disliked the prominence of body mass index (BMI) in the criteria, and all struggled with the proposed duration for recovery. Conceptually, the notion of recovery as an endpoint rather than a journey was contested.ConclusionsOur findings indicate disparities between academically derived recovery criteria and lived experiences and indicate perceived challenges in using such criteria in therapeutic settings. Including SUs and EDTs in the development of criteria may improve the likelihood of consolidating AN recovery criteria, but conceptual challenges remain.Practitioner pointsAN recovery is complex, and the use of research-based AN recovery criteria in therapeutic settings could have a detrimental effect on SUs' outcomes. EDTs should be aware of efforts to define AN recovery criteria. EDTs should engage with debates on defining AN recovery and seek to promote participation in such debates to SUs.

Project description:Anorexia nervosa (AN) is a devastating disorder with evidence of underexplored heritability. Twin and family studies estimate heritability (h2 ) to be 57%-64%, and genome-wide association studies (GWAS) reveal significant genetic correlations with psychiatric and anthropometric traits and a total of nine genome-wide significant loci. Whether significantly associated single nucleotide polymorphisms identified by GWAS are causal or tag true causal variants, remains to be elucidated. We propose a novel method for bridging this knowledge gap by fine-mapping short structural variants (SSVs) in and around GWAS-identified loci. SSV fine-mapping of loci associated with complex disorders such as schizophrenia, amyotrophic lateral sclerosis, and Alzheimer's disease has uncovered genetic risk markers, phenotypic variability between patients, new pathological mechanisms, and potential therapeutic targets. We analyze previous investigations' methods and propose utilizing an evaluation algorithm to prioritize 10 SSVs for each of the top two AN GWAS-identified loci followed by Sanger sequencing and fragment analysis via capillary electrophoresis to characterize these SSVs for case/control association studies. Success of previous SSV analyses in complex disorders and effective utilization of similar methodologies supports our proposed method. Furthermore, the structural and spatial properties of the 10 SSVs identified for each of the top two AN GWAS-associated loci, cell adhesion molecule 1 (CADM1) and NCK interacting protein with SH3 domain (NCKIPSD), are similar to previous studies. We propose SSV fine-mapping of AN-associated loci will identify causal genetic architecture. Deepening understandings of AN may lead to novel therapeutic targets and subsequently increase quality-of-life for individuals living with the illness. PUBLIC SIGNIFICANCE STATEMENT: Anorexia nervosa is a severe and complex illness, arising from a combination of environmental and genetic factors. Recent studies estimate the contribution of genetic variability; however, the specific DNA sequences and how they contribute remain unknown. We present a novel approach, arguing that the genetic variant class, short structural variants, could answer this knowledge gap and allow development of biologically targeted therapeutics, improving quality-of-life and patient outcomes for affected individuals.

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Contemporary views on the genetics of anorexia nervosa.

Publications

Contemporary views on the genetics of anorexia nervosa.

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