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Sodium-glucose cotransporter-1 inhibition and depression: A Mendelian randomization study
Gang Fan1,2,3, Hong Zuo2, Xun Shi2
1Clinical Research Center of Xianyang Central Hospital, Shaanxi Province, PR China.
Sodium-glucose cotransporter-1 inhibition may reduce depression risk in Europeans, according to Mendelian randomization. Sodium-glucose cotransporter-2 inhibition showed no significant association with depression risk.
Area of Science:
- Pharmacogenomics
- Neuroscience
- Metabolic Disorders
Background:
- Observational studies suggest a link between sodium-glucose cotransporter (SGLT) inhibitors and depression.
- Causal evidence is needed to confirm this association.
Purpose of the Study:
- To investigate the causal relationship between SGLT1/2 inhibition and depression risk.
- To leverage Mendelian randomization for robust genetic analysis.
Main Methods:
- Utilized 16 instrumental variables for SGLT1 and 6 for SGLT2 inhibition.
- Employed Mendelian randomization with random inverse variance weighted method.
- Analyzed depression data from Psychiatric Genomics Consortium and UK Biobank (n=500,199).
Main Results:
- Genetically predicted SGLT1 inhibition was associated with a reduced risk of depression in Europeans (OR=0.78, p=0.002).
- No significant causal association was found between SGLT2 inhibition and depression risk (OR=0.98, p=0.919).
Conclusions:
- SGLT1 inhibition may offer a protective effect against depression in the European population.
- Further research is warranted to elucidate the underlying mechanisms.
- This study provides genetic evidence supporting SGLT1 inhibition's potential role in managing depression.
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