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| PMID |
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| TITLE |
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| Mapping anorexia nervosa genes to clinical phenotypes. |
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| ABSTRACT |
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| BACKGROUND |
NlmCategory: BACKGROUND |
| Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes. |
| METHODS |
NlmCategory: METHODS |
| Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record 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™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations. |
| RESULTS |
NlmCategory: RESULTS |
| Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record 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™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations. Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex. |
| CONCLUSIONS |
NlmCategory: CONCLUSIONS |
| Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record 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™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations. Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex. Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| entrez |
2022/04/05 05:27 |
| pubmed |
2022/04/06 06:00 |
| medline |
2022/04/06 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Johnson JS |
|
Johnson |
Jessica S |
JS |
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Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY10029, USA. |
| Cote AC |
|
Cote |
Alanna C |
AC |
|
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY10029, USA. |
| Dobbyn A |
|
Dobbyn |
Amanda |
A |
|
Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY10029, USA. |
| Sloofman LG |
|
Sloofman |
Laura G |
LG |
|
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY10029, USA. |
| Xu J |
|
Xu |
Jiayi |
J |
|
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY10029, USA. |
| Cotter L |
|
Cotter |
Liam |
L |
|
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY10029, USA. |
| Charney AW |
|
Charney |
Alexander W |
AW |
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James J. Peters Department of Veterans Affairs Medical Center, Mental Illness Research, Education and Clinical Centers, Bronx, NY14068, USA. |
|
Eating Disorders Working Group of the Psychiatric Genomics Consortium |
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| Birgegård A |
|
Birgegård |
Andreas |
A |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Jordan J |
|
Jordan |
Jennifer |
J |
|
Department of Psychological Medicine, Christchurch School of Medicine & Health Sciences, University of Otago, 2 Riccarton Avenue, PO Box 4345, 8140Christchurch, New Zealand. |
| Kennedy M |
|
Kennedy |
Martin |
M |
|
Department of Psychological Medicine, Christchurch School of Medicine & Health Sciences, University of Otago, 2 Riccarton Avenue, PO Box 4345, 8140Christchurch, New Zealand. |
| Landén M |
|
Landén |
Mikaél |
M |
|
Institute of Neuroscience and Physiology, Sahlgrenska Academy at Gothenburg University, SE-413 45Gothenburg, Sweden. |
| Maguire SL |
|
Maguire |
Sarah L |
SL |
|
InsideOut Institute, University of Sydney, New South Wales2006, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Herston, QLD4029, Australia. |
| Mortensen PB |
|
Mortensen |
Preben Bo |
PB |
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National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark. |
| Thornton LM |
|
Thornton |
Laura M |
LM |
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Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC27517, USA. |
| Bulik CM |
|
Bulik |
Cynthia M |
CM |
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Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC27517, USA. |
| Huckins LM |
|
Huckins |
Laura M |
LM |
|
James J. Peters Department of Veterans Affairs Medical Center, Mental Illness Research, Education and Clinical Centers, Bronx, NY14068, USA. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: Psychological medicine |
| ISOABBREVIATION: Psychol Med |
| YEAR: 2022 |
| MONTH: Apr |
| DAY: 05 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1469-8978 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Psychol Med |
| COUNTRY: England |
| ISSNLINKING: 0033-2917 |
| NLMUNIQUEID: 1254142 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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AGENCY |
COUNTRY |
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Vetenskapsrådet (SE) |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| Anorexia nervosa |
| EHR |
| PrediXcan |
| pheWAS |
| transcriptomic imputation |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| CHEMICALS |
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