Hardy Dale S, Garvin Jane T, Leak-Johnson Tennille S, Mersha Tesfaye B
BioNutriOmics, Inc.
Walden University.
Res Sq. 2025 Aug 21:rs.3.rs-7105280. doi: 10.21203/rs.3.rs-7105280/v1.
It is unknown whether the impact of lifestyle could mitigate the genetically driven high-risk polygenic risk score (PRS) in different ancestries.
We determined associations and interactions between high-risk PRS, dietary patterns, physical activity, and metabolic burden and their impact on incident type 2 diabetes mellitus (T2DM) in European Americans and African Americans. A secondary aim determined ancestry-specific PRS-mapped genes associated molecular pathways.
Our longitudinal study (1976-2015) utilized de-identified data for European American (n = 8,283) and African American (n = 1,205) from 7-National Heart, Lung, and Blood Institute Candidate Gene Association Resource studies from the Database of Genotypes and Phenotypes. We assessed results using biased-corrected odds ratios (OR) and 95% confidence intervals (CI).
African Americans had a higher magnitude of incident T2DM risk for the high-risk PRS alone (OR = 1.61; 95% CI:1.22-2.12) than European Americans (OR = 1.24; 95% CI:1.06-1.45) in highest tertile compared to lowest tertile. We observed protective risks from incident T2DM with the Dietary Approaches to Stop High Blood Pressure (DASH) and Mediterranean diets (p < 0.025). However, entangling effects from the high-quality DASH/Mediterranean diets with the low-quality Southern diet and the high-risk PRS further increased T2DM risks (p < 0.025). The PRS-diet-physical activity associations had 9% protective T2DM risk for Mediterranean diet in African Americans and at least 5% for European Americans (p < 0.025). Interactions revealed the second tertile DASH and highest tertile Mediterranean diets in high-risk PRS-high metabolic burden, attenuated incident T2DM risk. Gene enrichment molecular pathways common to ancestries included neurogenerative diseases, lipid metabolism, and glucose metabolism.
Patients in the highest PRS tertiles with high metabolic burden could be targeted for early intervention to decrease T2DM risk. The DASH and Mediterranean diets with high physical activity should be recommended by clinicians for better prevention, detrimental molecular pathway reversal, and to decrease worsening of T2DM from high metabolic burden.
生活方式的影响是否能减轻不同种族中由基因驱动的高风险多基因风险评分（PRS）尚不清楚。
我们确定了高风险PRS、饮食模式、身体活动和代谢负担之间的关联及相互作用，以及它们对欧裔美国人和非裔美国人2型糖尿病（T2DM）发病的影响。第二个目标是确定特定种族的PRS映射基因相关的分子途径。
我们的纵向研究（1976 - 2015年）利用了来自基因型和表型数据库中7项美国国立心肺血液研究所候选基因关联资源研究的欧裔美国人（n = 8283）和非裔美国人（n = 1205）的去识别数据。我们使用偏差校正比值比（OR）和95%置信区间（CI）评估结果。
在最高三分位数与最低三分位数相比时，仅高风险PRS一项，非裔美国人发生T2DM的风险幅度（OR = 1.61；95% CI：1.22 - 2.12）高于欧裔美国人（OR = 1.24；95% CI：1.06 - 1.45）。我们观察到采用终止高血压饮食疗法（DASH）和地中海饮食可降低T2DM发病风险（p < 0.025）。然而，高质量的DASH/地中海饮食与低质量的南方饮食以及高风险PRS的交织效应进一步增加了T2DM风险（p < 0.025）。PRS - 饮食 - 身体活动关联对非裔美国人的地中海饮食有9%的T2DM保护风险，对欧裔美国人至少有5%的保护风险（p < 0.025）。相互作用显示，在高风险PRS - 高代谢负担情况下，第二三分位数的DASH饮食和最高三分位数的地中海饮食可降低T2DM发病风险。不同种族共有的基因富集分子途径包括神经退行性疾病、脂质代谢和葡萄糖代谢。
PRS最高三分位数且代谢负担高的患者可作为早期干预的目标，以降低T2DM风险。临床医生应推荐采用高身体活动水平的DASH饮食和地中海饮食，以更好地预防疾病、逆转有害分子途径，并减少高代谢负担导致的T2DM病情恶化。
