Sleep disturbances and insomnia are prevalent, with around 33% of adults indicating that they experience at least one main symptom of insomnia, and bidirectional relationships exist with common psychopathology, particularly major depressive disorder (MDD). However, genetic and environmental (e.g., traumatic event exposure) contributions to the etiology of these phenotypes are not yet well understood. A genetically informative sample of approximately 12,000 Han Chinese women aged 30-60 (50% with recurrent MDD) was used to address several gaps within the sleep literature. Sleep disturbances were assessed in all individuals using a general item addressing sleeplessness (GS). A sleep within depression sum score (SDS) was also created in MDD cases, combining information from the GS and two insomnia items within MDD. A total of 11 traumatic events were assessed and additional information on childhood sexual abuse (CSA) was also obtained. First, factor analyses were conducted to determine trauma factor structure. The best-fit solution included 3 factors: interpersonal, child interpersonal, and non-assaultive, and composite variables were constructed accordingly. A series of hierarchical regressions were run to examine differential effects of trauma type and timing on sleeplessness. All traumatic events predicted sleeplessness at similar magnitudes, although population models indicated that childhood interpersonal trauma may be particularly potent. An association between CSA and sleeplessness was also replicated. A series of genetic analyses demonstrated that the single nucleotide polymorphism-based heritability of sleep phenotypes did not differ significantly from zero. Further, association analyses did not identify any genome-wide significant loci. However, using a liberal false discovery rate threshold of 0.5, two genes of interest, KCNK9 and ALDH1A2, emerged for the SDS. Polygenic risk score (PRS) analyses demonstrated genetic overlap between the SDS in MDD cases and GS in MDD controls, with PRSs explaining 0.2-0.3% of the variance. A final combined model of both genetic and environmental risk indicated that both PRS and traumatic events were significant predictors of sleeplessness. While genetic results should be interpreted with caution given the lack of heritability, additional research into the genetic and environmental contributions to insomnia, utilizing more standardized phenotypes and properly ascertained samples, is clearly warranted.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-5801 |
| Date | 01 January 2017 |
| Creators | Lind, Mackenzie J |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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