@article {9646,
	title = {Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.},
	journal = {Epigenetics},
	volume = {19},
	year = {2024},
	month = {2024 Dec},
	pages = {2333668},
	abstract = {<p>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  = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (, , and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level ( < 1.2E-7). The downstream pathways affected by DNA methylation included the identification of  and  CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with , , and . 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.</p>},
	keywords = {C-Reactive Protein, CpG Islands, DNA, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study, Humans, Inflammation, Intracellular Signaling Peptides and Proteins},
	issn = {1559-2308},
	doi = {10.1080/15592294.2024.2333668},
	author = {Lundin, Jessica I and Peters, Ulrike and Hu, Yao and Ammous, Farah and Avery, Christy L and Benjamin, Emelia J and Bis, Joshua C and Brody, Jennifer A and Carlson, Chris and Cushman, Mary and Gignoux, Chris and Guo, Xiuqing and Haessler, Jeff and Haiman, Chris and Joehanes, Roby and Kasela, Silva and Kenny, Eimear and Lapalainien, Tuuli and Levy, Daniel and Liu, Chunyu and Liu, Yongmei and Loos, Ruth J F and Lu, Ake and Matise, Tara and North, Kari E and Park, Sungshim L and Ratliff, Scott M and Reiner, Alex and Rich, Stephen S and Rotter, Jerome I and Smith, Jennifer A and Sotoodehnia, Nona and Tracy, Russell and Van den Berg, David and Xu, Huichun and Ye, Ting and Zhao, Wei and Raffield, Laura M and Kooperberg, Charles}
}
@article {9911,
	title = {Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.},
	journal = {Clin Epigenetics},
	volume = {17},
	year = {2025},
	month = {2025 Apr 02},
	pages = {54},
	abstract = {<p>Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations. In addition, knowledge of nongenetic factors on lipid profiles is extremely limited. In the Population Architecture Using Genomics and Epidemiology (PAGE) Study, we performed methylome-wide association analysis on 9,561 participants from diverse race and ethnicity backgrounds for HDL-c, LDL-c, TC, and TG levels, and also tested interactions between smoking or alcohol intake and methylation in their association with lipid levels. We identified novel CpG sites at 16 loci (P < 1.18E-7) with successful replication on 3,215 participants. One additional novel locus was identified in the self-reported White participants (P = 4.66E-8). Although no additional CpG sites were identified in the genome-wide interaction analysis, 13 reported CpG sites showed significant heterogeneous association across smoking or alcohol intake strata. By mapping novel and reported CpG sites to genes, we identified enriched pathways directly linked to lipid metabolism as well as ones spanning various biological functions. These findings provide new insights into the regulation of lipid concentrations.</p>},
	keywords = {Adult, Aged, Alcohol Drinking, CpG Islands, DNA Methylation, Ethnicity, Female, Genome-Wide Association Study, Humans, Lipids, Male, Middle Aged, Racial Groups, Smoking, White People},
	issn = {1868-7083},
	doi = {10.1186/s13148-025-01859-3},
	author = {Hu, Yao and Haessler, Jeff and Lundin, Jessica I and Darst, Burcu F and Whitsel, Eric A and Grove, Megan and Guan, Weihua and Xia, Rui and Szeto, Mindy and Raffield, Laura M and Ratliff, Scott and Wang, Yuxuan and Wang, Xuzhi and Fohner, Alison E and Lynch, Megan T and Patel, Yesha M and Lani Park, S and Xu, Huichun and Mitchell, Braxton D and Bis, Joshua C and Sotoodehnia, Nona and Brody, Jennifer A and Psaty, Bruce M and Peloso, Gina M and Tsai, Michael Y and Rich, Stephen S and Rotter, Jerome I and Smith, Jennifer A and Kardia, Sharon L R and Reiner, Alex P and Lange, Leslie and Fornage, Myriam and Pankow, James S and Graff, Mariaelisa and North, Kari E and Kooperberg, Charles and Peters, Ulrike}
}
