Shared genetic mechanisms underlying association between sleep disturbances and depressive symptoms

Mariana Moyses-Oliveira; Malu Zamariolli; Priscila F Tempaku; Jose Carlos Fernandes Galduroz; Monica L Andersen; Sergio Tufik

doi:10.1016/j.sleep.2024.03.030

Shared genetic mechanisms underlying association between sleep disturbances and depressive symptoms

Sleep Med. 2024 Mar 24:119:44-52. doi: 10.1016/j.sleep.2024.03.030. Online ahead of print.

Authors

Mariana Moyses-Oliveira¹, Malu Zamariolli¹, Priscila F Tempaku¹, Jose Carlos Fernandes Galduroz², Monica L Andersen³, Sergio Tufik⁴

Affiliations

¹ Sleep Institute, Associacao Fundo de Incentivo a Pesquisa, Sao Paulo, Brazil.
² Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
³ Sleep Institute, Associacao Fundo de Incentivo a Pesquisa, Sao Paulo, Brazil; Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
⁴ Sleep Institute, Associacao Fundo de Incentivo a Pesquisa, Sao Paulo, Brazil; Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil. Electronic address: Sergio.Tufik@afip.com.br.

PMID: 38640740
DOI: 10.1016/j.sleep.2024.03.030

Abstract

Objectives: Polygenic scores (PGS) for sleep disturbances and depressive symptoms in an epidemiological cohort were contrasted. The overlap between genes assigned to variants that compose the PGS predictions was tested to explore the shared genetic bases of sleep problems and depressive symptoms.

Methods: PGS analysis was performed on the São Paulo Epidemiologic Sleep Study (EPISONO, N = 1042), an adult epidemiological sample. A genome wide association study (GWAS) for depression grounded the PGS calculations for Beck Depression Index (BDI), while insomnia GWAS based the PGS for Insomnia Severity Index (ISI) and Pittsburg Sleep Quality Index (PSQI). Pearson's correlation was applied to contrast PGS and clinical scores. Fisher's Exact and Benjamin-Hochberg tests were used to verify the overlaps between PGS-associated genes and the pathways enriched among their intersections.

Results: All PGS models were significant when individuals were divided as cases or controls according to BDI (R² = 1.2%, p = 0.00026), PSQI (R² = 3.3%, p = 0.007) and ISI (R² = 3.4%, p = 0.021) scales. When clinical scales were used as continuous variables, the PGS models for BDI (R² = 1.5%, p = 0.0004) and PSQI scores (R² = 3.3%, p = 0.0057) reached statistical significance. PSQI and BDI scores were correlated, and the same observation was applied to their PGS. Genes assigned to variants that compose the best-fit PGS predictions for sleep quality and depressive symptoms were significantly overlapped. Pathways enriched among the intersect genes are related to synapse function.

Conclusions: The genetic bases of sleep quality and depressive symptoms are correlated; their implicated genes are significantly overlapped and converge on neural pathways. This data suggests that sleep complaints accompanying depressive symptoms are not secondary issues, but part of the core mental illness.

Keywords: Depression; Insomnia; Neuropsychiatric disorders; Polygenic score; Sleep.