Depression in systemic lupus erythematosus: Modifiable or inheritable? a two-sample mendelian randomization study.

Area of Science:

• Genetics and Epidemiology
• Psychiatric Disorders
• Autoimmune Diseases

Background:

• Observational studies suggest a higher incidence of depression, a leading global disability, in patients with systemic lupus erythematosus (SLE).
• The underlying cause of this association remains unclear, with possibilities including genetic inheritance or modifiable factors like socioeconomic status.

Purpose of the Study:

• To investigate the potential causal relationship between genetically predicted SLE and depression using a two-sample Mendelian randomization analysis.
• To determine if the observed association between SLE and depression is attributable to inherited genetic factors.

Main Methods:

• Utilized single nucleotide polymorphisms (SNPs) associated with SLE from a genome-wide association study (GWAS) as instrumental variables (IVs).
• Employed large GWAS datasets for depression and major depressive disorder (MDD) as outcome variables.
• Applied the inverse-variance weighted (IVW) meta-analysis method (random-effects) to estimate the effects of IVs on depression and MDD.

Main Results:

• Genetically predicted SLE showed a decreased odds of depression (OR: 0.995; 95% CI: 0.990-0.999; p = 0.025).
• Genetically predicted SLE also demonstrated decreased odds of major depressive disorder (MDD) (OR: 0.985; 95% CI: 0.975-0.996; p = 0.009).
• The study achieved 90% power to detect a 4% increase in depression associated with SLE.

Conclusions:

• The findings indicate that the increased incidence of depression observed in patients with SLE is unlikely to be due to inheritable risk factors.
• This Mendelian randomization study suggests a protective genetic effect of SLE on depression, contradicting previous observational findings of increased risk.