The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression
Abstract
Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI…
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The FTO variant rs9939609 in human trials was associated with a lower risk of developing MDD.
“The FTO variant rs9939609 in human trials was associated with a lower risk of developing MDD.358”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [358]
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- Authors
- Samaan, Z., Anand, S., Zhang, X., Desai, D., Rivera, M., Pare, G., Thabane, L., Xie, C., Gerstein, H., Engert, J. C., Craig, I., Cohen-Woods, S., Mohan, V, Diaz, R., Wang, X., Liu, L., Corre, T., Preisig, M., Kutalik, Z., Bergmann, S., Vollenweider, P., Waeber, G., Yusuf, S., & Meyre, D.
- Affiliations
- Population Health Research Institute (CA)
- Universidad de Granada (ES)
- McGill University (CA)
- Madras Diabetes Research Foundation (IN)
- SIB Swiss Institute of Bioinformatics (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- McMaster University (CA)
- Corresponding author
- Meyre, D
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2012-11-20
- Volume
- 18
- Issue
- 12
- Pages
- 1281-1286
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2015751650
- Cited by
- 129
- References
- 51
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 13 · 2022: 6 · 2021: 36 · 2020: 9 · 2019: 7 · 2018: 3 · 2017: 10 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 5
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-03-05)
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- IRIS (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Canada Research Chairs
- Hamilton Health Sciences Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- depression, FTO, rs9939609, fat mass and obesity-associated gene, body mass index, genetic association, major depressive disorder, polygenic obesity
- MeSH terms
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Depression, Major Depressive Disorder, Female, Genotype, Humans, Male, Middle Aged, Obesity, Phenotype, Proteins, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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