Insomnia, Shorter Sleep Duration Linked to the Risk of Autoimmune Arthritis

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A recent study found insomnia and shorter sleep duration were linked to the risk of autoimmune arthritis, especially rheumatoid arthritis (RA).¹

“The analysis of genetic data relating to different sleep traits found that genetic predisposition to insomnia symptoms was associated with a higher risk of RA, where overall RA and nRA show the strongest associations,” wrote investigators, led by Yajia Li, MD, from the National Clinical Research Center for Geriatric Disorders, at Xiangya Hospital, in Changsha, China. “CAUSE analysis confirmed these results.”

People with autoimmune diseases often have sleep disorders, with insomnia being the most common one, which can dampen quality of life. Previous research found sleep duration was linked to chronic arthritis. Luckily for patients with RA, a recent study found exercising may improve their sleep quality.²

Li and colleagues aimed to evaluate the genetic causal relationship between sleep traits such as insomnia, sleep duration, nap during the day, chronotype, and narcolepsy with the risk of autoimmune arthritis. Types of autoimmune arthritis assessed included RA, ankylosing spondylitis (AS), and psoriatic arthritis (PsA).¹

To assess this relationship, the team used univariable and multivariable Mendelian randomization on genome-wide association studies. The primary analysis used the inverse-variance weighted method, and the secondary analysis used the CAUSE method.

Investigators leveraged data on sleep trait-associated single nucleotide polymorphisms from a large-scale perspective study with > 500,000 participants aged 37 – 73 years recruited from 2006 – 2010. They obtained data through questionnaires and physical measurements.

The team included participants with insomnia symptoms (n = 462,341), sleep duration (n = 460,099), nap during the day (n = 462,400), chronotype (n = 413,343), and narcolepsy (n = 460,9130. They also obtained data on body mass index (BMI), alcohol status, and smoking status from the GWAS database.

Data on hospital patients diagnosed with autoimmune diseases was obtained from the FinnGen GWAS database, a nationwide Finnish GAWS meta-analysis of 13 biobanks and cohorts. In the study, patients were diagnosed with RA (6236 cases, 147,221 controls), seropositive RA (pRA) (4596 cases, 172,834 controls), seronegative RA (nRA) (1937 cases, 172,834 controls), PsA (1455 cases, 217,337 controls), and AS (599 cases, 217,431 controls).

In univariable analyses, investigators found a significant link between insomnia symptoms and an increased risk of overall RA (odds ratio [OR], 2.76; 95% CI, 1.45 – 5.23; P = 1.91 x 10^-3) and nRA (OR, 6.95; 95% CI, 2.47 – 19.56; P = 2.41 x 10^-4). Additionally, they observed a relationship between napping during the day and AS (OR = 6.19, 95% CI, 1.23 – 31.27; P = 2.74 × 10⁻²) and a negative association between morning chronotype and overall RA (OR = 0.78, 95% CI, 0.61 – 0.99; P = 4.29 × 10⁻²). A negative association was also found between chronotype and pRA (OR = 0.71, 95% CI 0.53 – 0.95; P = 2.13 × 10⁻²).

They found no relationship between the sleep duration phenotype and autoimmune arthritis or between narcolepsy and AAs.

The CAUSE analysis also demonstrated an association between insomnia symptoms with overall RA (OR, 3.46, 95% CI, 2.75 – 4.39; P = 3.70 × 10⁻⁴) and with nRA (OR, 5.21, 95% CI, 3.42 – 7.77; P = 1.60 × 10⁻³).

After adjusting for body mass index (BMI), alcohol status, smoking status, and physical activity levels, multivariable analyses found genetic predisposition to overall RA (OR, 0.99, 95% CI, 0.97 – 1.00, P = 1.90 × 10⁻²) with decreased sleep duration. They also saw a significant genetic association between pRA and insomnia symptoms (OR, 1.01, 95% CI, 1.00 – 1.02, P = 3.50 × 10⁻²).

Limitations investigators highlighted included using a sample of only European descent, data coming from self-reported sleep traits, and the GWAS dataset was too small to detect subtle effects and adjust for possible pleiotropy.

The team concluded by saying how the study showed a potential bidirectional causal relationship between the genetic predisposition of insomnia symptoms and shorter sleep duration was linked to the risk of autoimmune arthritis, particularly RA. Predisposition to RA was also linked to reduced sleep duration and increased insomnia symptom risk.

“Strategies to reduce insomnia and prolong sleep duration could aid in the prevention of RA,” investigators wrote. “More attention should also be paid to sleep quality improvement for those with a genetic predisposition to RA."

^References

1. ^{Li Y, Li Q, Cao Z, Wu J. Causal association between sleep traits and autoimmune arthritis: Evidence from a bidirectional Mendelian randomization study. Sleep Health. Published online January 19, 2024. doi:10.1016/j.sleh.2023.11.014}
2. ^{Pine, L. Patients with RA Surprised by Positive Impact of Exercise on Sleep. HCPLive. February 2, 2024. https://www.hcplive.com/view/patients-with-ra-surprised-by-positive-impact-of-exercise-on-sleep. Accessed February 8, 2024.}