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Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa.

ABSTRACT: Anorexia nervosa (AN) is a heritable eating disorder (50-60%) with an array of commonly comorbid psychiatric disorders and related traits. Although significant genetic correlations between AN and psychiatric disorders and related traits have been reported, their shared genetic architecture is largely understudied. We investigated the shared genetic architecture of AN and schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), mood instability (Mood), neuroticism (NEUR), and intelligence (INT). We applied the conditional false discovery rate (FDR) method to identify novel risk loci for AN, and conjunctional FDR to identify loci shared between AN and related phenotypes, to summarize statistics from relevant genome-wide association studies (GWAS). Individual GWAS samples varied from 72,517 to 420,879 participants. Using conditional FDR we identified 58 novel AN loci. Furthermore, we identified 38 unique loci shared between AN and major psychiatric disorders (SCZ, BIP, and MD) and 45 between AN and psychological traits (Mood, NEUR, and INT). In line with genetic correlations, the majority of shared loci showed concordant effect directions. Functional analyses revealed that the shared loci are involved in 65 unique pathways, several of which overlapped across analyses, including the "signal by MST1" pathway involved in Hippo signaling. In conclusion, we demonstrated genetic overlap between AN and major psychiatric disorders and related traits, and identified novel risk loci for AN by leveraging this overlap. Our results indicate that some shared characteristics between AN and related disorders and traits may have genetic underpinnings.

SUBMITTER: Bang L

PROVIDER: S-EPMC10474135 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa.

Bang Lasse L Bahrami Shahram S Hindley Guy G Smeland Olav B OB Rødevand Linn L Jaholkowski Piotr P PP Shadrin Alexey A Connell Kevin S O' KSO Frei Oleksandr O Lin Aihua A Rahman Zillur Z Cheng Weiqiu W Parker Nadine N Fan Chun C CC Dale Anders M AM Djurovic Srdjan S Bulik Cynthia M CM Andreassen Ole A OA

Translational psychiatry 20230901 1

Anorexia nervosa (AN) is a heritable eating disorder (50-60%) with an array of commonly comorbid psychiatric disorders and related traits. Although significant genetic correlations between AN and psychiatric disorders and related traits have been reported, their shared genetic architecture is largely understudied. We investigated the shared genetic architecture of AN and schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), mood instability (Mood), neuroticism (NEUR), and intellige ...[more]

PMID: 37658054

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Project description:ObjectiveLittle is known about how individuals with atypical anorexia nervosa (AN) respond to eating disorder (ED) treatment in a partial hospitalization program (PHP), nor how certain factors such as trauma, childhood abuse, psychiatric comorbidity, and suicidal thoughts and behaviors might contribute to poor treatment outcomes. Thus, the current study (1) compares prevalence of these factors between individuals with AN and atypical AN upon admission to an ED PHP, (2) compares PHP treatment response between groups, and (3) investigates whether experiencing these factors impacts treatment outcomes.MethodWe conducted a retrospective chart review of young adults admitted to a PHP with AN (n = 95) and atypical AN (n = 59). Histories of psychiatric comorbidities and adverse childhood experiences were obtained from initial psychiatric evaluations. ED symptoms were assessed at intake and discharge with the Eating Disorder Examination-Questionnaire (EDE-Q).ResultsNo significant differences were found at intake in ED symptom severity or prevalence of lifetime trauma, childhood abuse, number of psychiatric diagnoses, or suicidal thoughts and behavior. Symptomatology at discharge also did not differ between groups. Emotional abuse was significantly related to discharge shape and weight overvaluation. No other intake characteristics were significantly related to discharge symptomatology.DiscussionTo our knowledge, this is the first study to compare the prevalence of comorbidities for both AN and atypical AN, as well as differential treatment outcomes for these individuals in a PHP. Results add to growing literature suggesting that, other than weight, AN and atypical AN have few properties that reliably distinguish them from one another.Public significanceThis study adds to a growing body of literature that raises questions about whether anorexia nervosa (AN) and atypical AN are truly different diagnoses. Our findings suggest these two groups present to treatment in a partial hospitalization program (PHP) with similar ED symptoms, as well as prevalence of lifetime trauma, childhood abuse, suicidal thoughts and behavior, and number of psychiatric comorbidities, and demonstrate similar treatment trajectories in PHP.

Dataset Information

Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa.

Publications

Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa.

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