Can your sleep predict depression? Insights from a genetic study

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In a recent study published in Translational Psychiatry, researchers conducted a prospective study using a population-based cohort to calculate polygenic scores and understand whether suboptimal sleep durations indicated a predisposition to depression and vice versa.

Study: Polygenic predisposition, sleep duration, and depression: evidence from a prospective population-based cohort. Image Credit: Leszek Glasner/Shutterstock.com
Study: Polygenic predisposition, sleep duration, and depression: evidence from a prospective population-based cohort. Image Credit: Leszek Glasner/Shutterstock.com

Background

Short or long sleep durations comprising five to six hours or eight to 10 hours, respectively, are both considered suboptimal and are believed to contribute significantly to the health concerns faced by elder, community-dwelling adults. Given that the prevalence of depression is the highest among adults between the ages of 55 and 74, and increasing age is linked to a decrease in optimal sleep durations, suboptimal sleep durations may be prodromal indicators of depression.

Epidemiological and clinical studies have reported that suboptimal durations of sleep and depression have a comorbid and bidirectional relationship, with some evidence indicating that both long and short sleep durations are indicators of the onset of depression, while other studies reporting that depression results in suboptimal durations of sleep.

Furthermore, although environmental factors are known to contribute to the onset of depression and suboptimal sleep durations, the traits related to both these factors are largely heritable, as understood from various twin studies.

About the study

In the present study, the researchers used polygenic scores across a phenotypically defined, large, prospective cohort of older adults in the UK to determine whether polygenic disposition to suboptimal sleep durations plays a role in the development and onset of depression and vice versa.

Polygenic scores are indicators of the genetic propensity of an individual for a trait. They are calculated using the total sum of the number of alleles across the genome associated with a trait, also called single-nucleotide polymorphisms, weighted by the association effect size obtained from genome-wide association studies.

The sleep thresholds used to define short and long sleep durations — five to seven hours and eight to nine hours, respectively — were based on the curvilinear risk of sleep durations on depression obtained from a meta-analysis of various prospective studies. The data for the study was obtained from a multi-disciplinary prospective study known as the English Longitudinal Study of Aging involving adults above 50, which began in 2002 and has been conducting biannual assessments since.

The baseline genetic data was obtained from the assessments between 2004 and 2006, while the data for analyzing outcomes of depression and sleep durations was derived from the assessments conducted between 2012 and 2016. The data was collected through computer-assisted interviews and nurse visits to the participants’ homes.

Open-ended questions measured sleep duration, while an eight-item depression scale was used to evaluate self-reported depression episodes. Other covariates included in the analysis were age, sex, and genetic ancestry. The genetic data was obtained through a genome-wide genotyping method that covers approximately 2.5 million genetic markers with a capture accuracy of 2.5% minor allele frequency variation.

The summary statistics from the genome-wide association study from the UK Biobank were used to calculate the polygenic scores for short and long sleep durations and overall sleep duration across an eight-year follow-up period.

Results

The results indicated that a single standard deviation increase in polygenic risk scores for short sleep duration was linked to a 14% increase in the odds of the onset of depression. The polygenic risk scores for long sleep duration or overall sleep duration, however, were not associated with the onset of depression. Furthermore, the polygenic risk scores for depression were not conversely associated with overall, long, or short sleep durations.

The absence of an association between depression and sleep durations, despite the association between short sleep and depression onset, indicated that the underlying mechanisms differ significantly based on the direction of the association.

Some of the theorized mechanisms to explain the relationship between short sleep durations and depression onset include abnormal circadian rhythms, electroencephalogram abnormalities such as prolonged duration of rapid eye movement sleep, and hyperactivity of the hypothalamic-pituitary-adrenal axis.

Furthermore, the variation in the association between short and long sleep durations and the onset of depression can also be linked to different molecular mechanisms. Studies have found that the single-nucleotide polymorphism linked to short sleep was in the proximity of the AUTS2 or activator of transcription and developmental regulator gene, while that linked to long sleep duration was closer to the MAPKAP1 or mitogen-activated protein kinase-associated protein 1 gene and mutations in both genes have been linked to different disorders.

Conclusions

Overall, the findings suggested that a genetic predisposition to short durations of sleep among older adults was associated with a higher probability of depression onset, but overall sleep durations and long durations of sleep had no relationship with depression. However, the converse relationship was not observed, and a genetic predisposition to depression had no associations with short or long sleep durations.

Journal reference:
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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