The Phenome-wide Consequences of Anorexia Nervosa Genes
Jessica S Johnson,
Alanna C Cote,
Laura G Sloofman,
Eating Disorders Working Group of the Psychiatric Genomics Consortium,
Martin A Kennedy,
Sarah L Maguire,
Nicholas G Martin,
Preben Bo Mortensen,
Laura M Huckins
Posted 18 Feb 2021
medRxiv DOI: 10.1101/2021.02.12.21250941
Posted 18 Feb 2021
Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional GWAS studies produce principal evidence for the association of genetic variants with disease, and provide a jumping-off point for downstream functional analyses. Transcriptomic imputation (TI) allows for the translation of SNPs into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a more broad setting through the use of phenome-wide association studies (PheWAS) in large and diverse clinical biobank populations with electronic health record (EHR) phenotypes. 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 PheWAS on over 2000 clinical outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of BMI on AN-GReX clinical associations. Our S-PrediXcan analysis identified 47 genes associated with AN, including what is, to our knowledge, the first genetic association of AN with the Major Histocompatibility Complex (MHC). AN-GReX was associated with autoimmune, anthropometric, metabolic, psychiatric and gastrointestinal diagnoses in our biobank cohort, as well as measures of anthropometry, substance use, and pain score. Our analyses reveal that AN-GReX associations with measures of weight and substance use are modified by BMI, and indicate potential avenues of functional mechanism to investigate further.
- Downloaded 260 times
- Download rankings, all-time:
- Site-wide: 93,790
- In genetic and genomic medicine: 360
- Year to date:
- Site-wide: 7,462
- Since beginning of last month:
- Site-wide: 4,591
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!