Genetic overlap between major depressive disorder and obstructive sleep apnea

Area of Science:

• Genetics
• Psychiatry
• Sleep Medicine

Background:

• Obstructive sleep apnea (OSA) frequently co-occurs with psychiatric disorders, notably major depressive disorder (MDD).
• Understanding the shared genetic underpinnings is crucial for elucidating common pathological mechanisms.

Purpose of the Study:

• To investigate the genetic overlap between MDD and OSA.
• To explore potential causal relationships and shared genetic factors between these two conditions.

Main Methods:

• Genome-wide association studies (GWAS) for OSA and MDD.
• Linkage disequilibrium score regression (LDSC) for genetic correlation.
• Cross-Phenotype Association (CPASSOC), Colocalization (COLOC), and Multi-marker Analysis of GenoMic Annotation (MAGMA) for pleiotropy.
• Mendelian randomization (MR) for causal inference.

Main Results:

• Significant genetic correlation (rg=0.31, P < 1.42E-23) and high heritability for both MDD and OSA.
• Identification of 397 pleiotropic single-nucleotide polymorphisms (SNPs) and 154 pleiotropic genes, including PCLO.
• Mendelian randomization indicated that MDD causally increases the risk of OSA (OR=1.28).

Conclusions:

• MDD and OSA share common genetic factors, with PCLO identified as a shared gene.
• MDD is a causal risk factor for the development of OSA.
• These findings provide insights into the shared pathophysiology of comorbid MDD and OSA.