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. 2025 May 28;8(1):821.
doi: 10.1038/s42003-025-08226-1.

Methylation risk score of C-reactive protein associates sleep health with related health outcomes

Ziqing Wang  1   2 , Danielle A Wallace  3   4   5   6 , Brian W Spitzer  3 , Tianyi Huang  7 , Kent D Taylor  8 , Jerome I Rotter  8 , Stephen S Rich  9 , Peter Y Liu  10 , Martha L Daviglus  11 , Lifang Hou  11 , Alberto R Ramos  12 , Sonya Kaur  12 , J Peter Durda  13 , Hector M González  14 , Myriam Fornage  15   16 , Susan Redline  4   5 , Carmen R Isasi  17 , Tamar Sofer  18   19   20   21
Affiliations

Methylation risk score of C-reactive protein associates sleep health with related health outcomes

Ziqing Wang et al. Commun Biol. .

Abstract

C-reactive protein (CRP) reflects inflammation status and is linked to poor sleep, metabolic and cardiovascular health. Methylation (MRS) and polygenic risk scores (PRS) reflect long-term systemic inflammation, and genetically-determined CRP, respectively. To refine understanding of inflammation-linked sleep and health outcomes, we construct PRS-CRPs using GWAS summary statistics and a previously-developed MRS-CRP in the Hispanic Community Health Study/Study of Latinos. Via survey-weighted linear regression, we estimate associations between blood-, PRS-, and MRS-CRP, with multiple sleep and health outcomes (n = 2217). MRS-CRP and PRS-CRPs are associated with increasing blood-CRP level by 43% and 23% per standard deviation. MRS-CRP is associated with obstructive sleep apnea (OSA) traits, long sleep duration, diabetes and hypertension, while PRS-CRPs were not. Blood-CRP level is associated with sleep duration and diabetes. Adjusting for MRS-CRP weakens OSA-diabetes/hypertension associations. Consequently, MRS-CRP is a stronger marker than blood-CRP and PRS-CRP to systemic inflammation associated with poor sleep and related comorbidities.

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Conflict of interest statement

Competing interests: The author declare no competing of interests. Ethics statement: H.C.H.S./S.O.L.: This study was approved by the institutional review boards (IRBs) at each field center, where all participants gave written informed consent, and by the Non-Biomedical IRB at the University of North Carolina at Chapel Hill, to the HCHS/SOL Data Coordinating Center. All IRBs approving the study are: Non-Biomedical IRB at the University of North Carolina at Chapel Hill. Chapel Hill, NC; Einstein IRB at the Albert Einstein College of Medicine of Yeshiva University. Bronx, NY; IRB at Office for the Protection of Research Subjects (OPRS), University of Illinois at Chicago. Chicago, IL; Human Subject Research Office, University of Miami. Miami, FL; Institutional Review Board of San Diego State University. San Diego, CA. MESA: All MESA participants provided written informed consent, and the study was approved by the Institutional Review Boards at The Lundquist Institute (formerly Los Angeles BioMedical Research Institute) at Harbor-UCLA Medical Center, University of Washington, Wake Forest School of Medicine, Northwestern University, University of Minnesota, Columbia University, and Johns Hopkins University. This work was approved by the Beth Israel Deaconess Medical Center Committee on Clinical Investigators (protocol #2023P000538).

Figures

Fig. 1
Fig. 1. Study design.
The associations of circulating CRP with Methylation risk score (MRS) and PRS constructed in HCHS/SOL was confirmed before evaluating the association of these CRP measures with sleep and other health outcomes. HCHS/SOL: Hispanic Community Health Study/Study of Latinos. SLR: Survey linear regression. MRS: methylation risk score; PRS: polygenic risk score.
Fig. 2
Fig. 2. Association of polygenic risk score (PRS) and methylation risk score (MRS) for C-reactive protein (CRP) with blood CRP level.
PRS-EUR: PRS-CRP developed as the European-specific PRS from the PRS-CSx analysis; PRS-wsum: PRS-CRP taken as the weighted sum of ancestry-specific PRS-CSx PRSs.
Fig. 3
Fig. 3. Forest plot showing associations between C-reactive protein (CRP) measures and measured health outcomes.
A Obstructive sleep apnea (OSA), sleep duration and cognitive traits; (B) odds ratio for binary cardio-metabolic and other sleep outcomes. From left to right model coefficients or odds ratio in case of binary outcomes, 95% confidence interval (95% CI), p value (p.val) and FDR corrected q value (q.val). MRS: methylation risk score; PRS: polygenic risk score; REI: respiratory event index; SpO2: hemoglobin oxygen saturation; % Time SpO2 < 90: the percentage of cumulative time with SpO2 below 90% in total sleep time.
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