Dataset Information

Eating disorder predisposition is associated with ESRRA and HDAC4 mutations.

ABSTRACT: Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mapping or by whole-exome sequencing. In the first family, analysis of twenty members across three generations identified a rare missense mutation in the estrogen-related receptor ? (ESRRA) gene that segregated with illness. In the second family, analysis of eight members across four generations identified a missense mutation in the histone deacetylase 4 (HDAC4) gene that segregated with illness. ESRRA and HDAC4 were determined to interact both in vitro in HeLa cells and in vivo in mouse cortex. Transcriptional analysis revealed that HDAC4 potently represses the expression of known ESRRA-induced target genes. Biochemical analysis of candidate mutations revealed that the identified ESRRA mutation decreased its transcriptional activity, while the HDAC4 mutation increased transcriptional repression of ESRRA. Our findings suggest that mutations that result in decreased ESRRA activity increase the risk of developing EDs.

SUBMITTER: Cui H

PROVIDER: S-EPMC3809805 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Eating disorder predisposition is associated with ESRRA and HDAC4 mutations.

Cui Huxing H Moore Jarrette J Ashimi Sunbola S SS Mason Brittany L BL Drawbridge Jordan N JN Han Shizhong S Hing Benjamin B Matthews Abigail A McAdams Carrie J CJ Darbro Benjamin W BW Pieper Andrew A AA Waller David A DA Xing Chao C Lutter Michael M

The Journal of clinical investigation 20131101 11

Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mapping or by whole-exome sequencing. In the first family, analysis of twenty members across three generation ...[more]

PMID: 24216484

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Dataset Information

Eating disorder predisposition is associated with ESRRA and HDAC4 mutations.

Publications

Eating disorder predisposition is associated with ESRRA and HDAC4 mutations.

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