A comprehensive lifestyle index and its associations with DNA methylation and type 2 diabetes among Ghanaian adults: the rodam study.

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2024-10-16 DOI:10.1186/s13148-024-01758-z

C A Abidha, K A C Meeks, F P Chilunga, A Venema, R Schindlmayr, C Hayfron-Benjamin, Kerstin Klipstein-Grobusch, Frank P Mockenhaupt, C Agyemang, P Henneman, I Danquah

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引用次数: 0

Abstract

Background: A series of modifiable lifestyle factors, such as diet quality, physical activity, alcohol intake, and smoking, may drive the rising burden of type 2 diabetes (T2DM) among sub-Saharan Africans globally. It is unclear whether epigenetic changes play a mediatory role in the associations between these lifestyle factors and T2DM. We assessed the associations between a comprehensive lifestyle index, DNA methylation and T2DM among Ghanaian adults.

Methods: We used whole-blood Illumina 450 k DNA methylation data from 713 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. We constructed a comprehensive lifestyle index based on established cut-offs for diet quality, physical activity, alcohol intake, and smoking status. In the T2DM-free discovery cohort (n = 457), linear models were fitted to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) associated with the lifestyle index after adjustment for age, sex, body mass index (BMI), and technical covariates. Associations between the identified DMPs and the primary outcome (T2DM), as well as secondary outcomes (fasting blood glucose (FBG) and HbA1c), were determined via logistic and linear regression models, respectively.

Results: In the present study population (mean age: 52 ± 10 years; male: 42.6%), the comprehensive lifestyle index showed a significant association with one DMP annotated to an intergenic region on chromosome 7 (false discovery rate (FDR) = 0.024). Others were annotated to ADCY7, SMARCE1, AHRR, LOXL2, and PTBP1 genes. One DMR was identified and annotated to the GFPT2 gene (familywise error rate (FWER) from bumphunter bootstrap = 0.036). None of the DMPs showed significant associations with T2DM; directions of effect were positive for the DMP in the AHRR and inverse for all the other DMPs. Higher methylation of the ADCY7 DMP was associated with higher FBG (p = 0.024); LOXL2 DMP was associated with lower FBG (p = 0.023) and HbA1c (p = 0.049); and PTBP1 DMP was associated with lower HbA1c (p = 0.002).

Conclusions: In this explorative epigenome-wide association study among Ghanaians, we identified one DMP and DMR associated with a comprehensive lifestyle index not previously associated with individual lifestyle factors. Based on our findings, we infer that lifestyle factors in combination, affect DNA methylation, thereby influencing the risk of T2DM among Ghanaian adults living in different contexts.

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加纳成年人的综合生活方式指数及其与 DNA 甲基化和 2 型糖尿病的关系：罗丹研究。

背景：一系列可改变的生活方式因素，如饮食质量、体育锻炼、酒精摄入量和吸烟，可能导致全球撒哈拉以南非洲人患 2 型糖尿病（T2DM）的负担不断增加。目前还不清楚表观遗传变化是否在这些生活方式因素与 T2DM 的关联中起着中介作用。我们评估了加纳成年人的综合生活方式指数、DNA 甲基化和 T2DM 之间的关联：我们使用了非洲移民肥胖和糖尿病研究（RODAM）中 713 名加纳人的全血 Illumina 450 k DNA 甲基化数据。我们根据饮食质量、运动量、酒精摄入量和吸烟状况的既定临界值构建了综合生活方式指数。在无 T2DM 的发现队列（n = 457）中，我们拟合了线性模型，以确定在调整年龄、性别、体重指数（BMI）和技术协变量后与生活方式指数相关的差异甲基化位置（DMPs）和差异甲基化区域（DMRs）。通过逻辑回归模型和线性回归模型分别确定了已确定的 DMP 与主要结果（T2DM）和次要结果（空腹血糖 (FBG) 和 HbA1c）之间的关系：在本研究人群（平均年龄：52 ± 10 岁；男性：42.6%）中，综合生活方式指数与注释在 7 号染色体基因间区域的一个 DMP 有显著关联（误发现率 (FDR) = 0.024）。其他DMP被注释为ADCY7、SMARCE1、AHRR、LOXL2和PTBP1基因。一个 DMR 被鉴定并注释为 GFPT2 基因（来自 bumphunter bootstrap 的家族误差率 (FWER) = 0.036）。没有一个 DMP 与 T2DM 有显著关联；AHRR 中的 DMP 的影响方向为正，而所有其他 DMP 的影响方向为反。ADCY7 DMP的甲基化程度较高与较高的FBG相关（p = 0.024）；LOXL2 DMP与较低的FBG（p = 0.023）和HbA1c（p = 0.049）相关；PTBP1 DMP与较低的HbA1c相关（p = 0.002）：在这项对加纳人进行的全表观基因组关联探索性研究中，我们发现了一个与综合生活方式指数相关的DMP和DMR，而这在以前与单个生活方式因素无关。根据我们的研究结果，我们推断生活方式因素结合在一起会影响 DNA 甲基化，从而影响生活在不同环境中的加纳成年人患 T2DM 的风险。

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.