Center for Research on People of Color, Columbia University School of Nursing, New York, New York, USA.
Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, USA.
Obesity (Silver Spring). 2023 Jan;31(1):243-255. doi: 10.1002/oby.23589. Epub 2022 Dec 7.
Obesity is a significant public health concern across the globe. Research investigating epigenetic mechanisms related to obesity and obesity-associated conditions has identified differences that may contribute to cellular dysregulation that accelerates the development of disease. However, few studies include Black women, who experience the highest incidence of obesity and early onset of cardiometabolic disorders.
The association of BMI with epigenome-wide DNA methylation (DNAm) was examined using the 850K Illumina EPIC BeadChip in two Black populations (Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure [InterGEN], n = 239; and The Genetic Epidemiology Network of Arteriopathy [GENOA] study, n = 961) using linear mixed-effects regression models adjusted for batch effects, cell type heterogeneity, population stratification, and confounding factors.
Cross-sectional analysis of the InterGEN discovery cohort identified 28 DNAm sites significantly associated with BMI, 24 of which had not been previously reported. Of these, 17 were replicated using the GENOA study. In addition, a meta-analysis, including both the InterGEN and GENOA cohorts, identified 658 DNAm sites associated with BMI with false discovery rate < 0.05. In a meta-analysis of Black women, we identified 628 DNAm sites significantly associated with BMI. Using a more stringent significance threshold of Bonferroni-corrected p value 0.05, 65 and 61 DNAm sites associated with BMI were identified from the combined sex and female-only meta-analyses, respectively.
This study suggests that BMI is associated with differences in DNAm among women that can be identified with DNA extracted from salivary (discovery) and peripheral blood (replication) samples among Black populations across two cohorts.
肥胖是全球范围内一个重大的公共卫生关注点。研究肥胖症和肥胖相关疾病的表观遗传机制，已经确定了可能导致细胞失调从而加速疾病发展的差异。然而，很少有研究纳入肥胖症和心血管代谢疾病发病早的发生率最高的黑人女性。
采用线性混合效应回归模型，使用 850K Illumina EPIC BeadChip，在两个黑人人群中（遗传和心理因素对血压的代际影响[InterGEN]，n=239；动脉粥样硬化遗传流行病学网络[GENOA]研究，n=961），对 BMI 与全基因组 DNA 甲基化（DNAm）的关联进行了检查，模型经过了批次效应、细胞类型异质性、人群分层和混杂因素的调整。
InterGEN 发现队列的横断面分析确定了 28 个与 BMI 显著相关的 DNAm 位点，其中 24 个以前没有报道过。其中，17 个在 GENOA 研究中得到了复制。此外，一项包括 InterGEN 和 GENOA 两个队列的荟萃分析确定了 658 个与 BMI 相关且假发现率<0.05 的 DNAm 位点。在对黑人女性的荟萃分析中，我们确定了 628 个与 BMI 显著相关的 DNAm 位点。使用 Bonferroni 校正的 p 值<0.05 的更严格显著阈值，在联合性别和女性仅有的荟萃分析中，分别确定了 65 个和 61 个与 BMI 相关的 DNAm 位点。
这项研究表明，BMI 与黑人女性 DNAm 中的差异有关，这些差异可以通过从两个队列中的唾液（发现）和外周血（复制）样本中提取的 DNA 识别出来。
