Dataset Information

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

ABSTRACT: Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p < 1.2E-7). The downstream pathways affected by DNA methylation included the identification of IFI16 and IRF7 CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with NLRC5, NOD2, and AIM2. Gene enrichment analysis also identified the nuclear factor-kappaB transcription pathway. Using two-sample Mendelian randomization (MR) we inferred methylation at three CpG sites as causal for CRP levels using both White and Black or African American MR instrument variables. Overall, we identified novel CpG sites and gene transcripts that could be valuable in understanding the specific cellular processes and pathogenic mechanisms involved in inflammation.

SUBMITTER: Lundin JI

PROVIDER: S-EPMC10996836 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature

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Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

Lundin Jessica I JI Peters Ulrike U Hu Yao Y Ammous Farah F Avery Christy L CL Benjamin Emelia J EJ Bis Joshua C JC Brody Jennifer A JA Carlson Chris C Cushman Mary M Gignoux Chris C Guo Xiuqing X Haessler Jeff J Haiman Chris C Joehanes Roby R Kasela Silva S Kenny Eimear E Lapalainien Tuuli T Levy Daniel D Liu Chunyu C Liu Yongmei Y Loos Ruth J F RJF Lu Ake A Matise Tara T North Kari E KE Park Sungshim L SL Ratliff Scott M SM Reiner Alex A Rich Stephen S SS Rotter Jerome I JI Smith Jennifer A JA Sotoodehnia Nona N Tracy Russell R Van den Berg David D Xu Huichun H Ye Ting T Zhao Wei W Raffield Laura M LM Kooperberg Charles C

Epigenetics 20240403 1

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory me ...[more]

PMID: 38571307

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Project description:ImportanceNeuroimaging studies have documented racial and ethnic disparities in brain health in old age. It remains unclear whether these disparities are apparent in midlife.ObjectiveTo assess racial and ethnic disparities in magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration in midlife and late life.Design, setting, and participantsData from 2 community-based cohort studies, Washington Heights-Inwood Columbia Aging Project (WHICAP) and the Offspring Study of Racial and Ethnic Disparities in Alzheimer Disease (Offspring), were used. Enrollment took place from March 2011 and June 2017, in WHICAP and Offspring, respectively, to January 2021. Of the 822 Offspring and 1254 WHICAP participants approached for MRI scanning, 285 and 176 refused participation in MRI scanning, 36 and 76 were excluded for contraindications/ineligibility, and 4 and 32 were excluded for missing key variables, respectively.Main outcomes and measuresCortical thickness in Alzheimer disease-related regions, white matter hyperintensity (WMH) volume.ResultsThe final sample included 1467 participants. Offspring participants (497 [33.9%]) had a mean (SD) age of 55 (10.7) years, had a mean (SD) of 13 (3.5) years of education, and included 117 Black individuals (23.5%), 348 Latinx individuals (70%), 32 White individuals (6.4%), and 324 women (65.2%). WHICAP participants (970 [66.1%]) had a mean (SD) age of 75 (6.5) years, had a mean (SD) of 12 (4.7) years of education, and included 338 Black individuals (34.8%), 389 Latinx individuals (40.1%), 243 White individuals (25.1%), and 589 women (65.2%). Racial and ethnic disparities in cerebrovascular disease were observed in both midlife (Black-White: B = 0.357; 95% CI, 0.708-0.007; P = .046) and late life (Black-Latinx: B = 0.149, 95% CI, 0.068-0.231; P < .001; Black-White: B = 0.166; 95% CI, 0.254-0.077; P < .001), while disparities in cortical thickness were evident in late life only (Black-Latinx: B = -0.037; 95% CI, -0.055 to -0.019; P < .001; Black-White: B = -0.064; 95% CI -0.044 to -0.084; P < .001). Overall, Black-White disparities were larger than Latinx-White disparities for cortical thickness and WMH volume. Brain aging, or the association of age with MRI measures, was greater in late life compared with midlife for Latinx (cortical thickness: B = 0.006; 95% CI, 0.004-0.008; P < .001; WMH volume: B = -0.010; 95% CI, -0.018 to -0.001; P = .03) and White (cortical thickness: B = 0.005; 95% CI, 0.002-0.008; P = .001; WMH volume: B = -0.021; 95% CI -0.043 to 0.002; P = .07) participants but not Black participants (cortical thickness: B = 0.001; 95% CI, -0.002 to 0.004; P =.64; WMH volume: B = 0.003; 95% CI, -0.010 to 0.017; P = .61), who evidenced a similarly strong association between age and MRI measures in midlife and late life.Conclusions and relevanceIn this study, racial and ethnic disparities in small vessel cerebrovascular disease were apparent in midlife. In Latinx and White adults, brain aging was more pronounced in late life than midlife, whereas Black adults showed accelerated pattern of brain aging beginning in midlife.

Project description:BackgroundOlder age and medical comorbidities are identified risk factors for developing severe coronavirus disease 2019. However, there are limited data on risk stratification, clinical and laboratory course, and optimal management of coronavirus disease 2019 in pregnancy.ObjectiveOur study aimed to describe the clinical course of coronavirus disease 2019, effect of comorbidities on disease severity, laboratory trends, and pregnancy outcomes of symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2-positive pregnant women.Study designThis is a case series of pregnant and postpartum women who received positive test results for severe acute respiratory syndrome coronavirus 2 between March 3, 2020, and May 11, 2020, within 3 hospitals of the Yale New Haven Health delivery network. Charts were reviewed for basic sociodemographic and prepregnancy characteristics, coronavirus disease 2019 course, laboratory values, and pregnancy outcomes.ResultsOf the 1567 tested pregnant and postpartum women between March 3, 2020, and May 11, 2020, 9% (n=141) had a positive severe acute respiratory syndrome coronavirus 2 result. Hispanic women were overrepresented in the severe acute respiratory syndrome coronavirus 2-positive group (n=61; 43.8%). In addition, Hispanic ethnicity was associated with a higher rate of moderate and severe diseases than non-Hispanic (18% [11/61] vs 3.8% [3/78], respectively; odds ratio, 5.5; 95% confidence interval, 1.46-20.7; P=.01). Of note, 44 women (31.2%) were asymptomatic, 37 of whom (26.2%) were diagnosed on universal screening upon admission for delivery. Moreover, 59% (n=83) were diagnosed before delivery, 36% (n=51) upon presentation for childbirth, and 5% (n=7) after delivery. Severe disease was diagnosed in 6 cases (4.3%), and there was 1 maternal death. Obese women were more likely to develop moderate and severe diseases than nonobese women (16.4% [9/55] vs 3.8% [3/79]; odds ratio, 4.96; 95% confidence interval, 1.28-19.25; P=.02). Hypertensive disorders of pregnancy were diagnosed in 22.3% of women (17/77) who delivered after 20 weeks' gestation. Higher levels of C-reactive protein during antepartum coronavirus disease 2019-related admission were more common in women with worse clinical course; however, this association did not reach statistical significance.ConclusionCoronavirus disease 2019 in pregnancy may result in severe disease and death. Hispanic women were more likely to receive a positive test result for severe acute respiratory syndrome 2 than other ethnic groups. Obesity and Hispanic ethnicity represent risk factors for moderate and severe diseases.

Dataset Information

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

Publications

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

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