Considerations for study design and analysis for ethically and culturally safe DNA methylation research in Aotearoa New Zealand

Epigenetic research, particularly DNA methylation (DNAm), holds significant potential for improving cardiovascular disease (CVD) risk prediction, yet its application must be guided by ethical and culturally responsive considerations. This paper examines the integration of a values-based framework to ensure the culturally safe conduct of DNAm research within the Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) cohort. Grounded in Te Tiriti o Waitangi principles and kaupapa Māori methodologies, this study emphasises equity, social accountability, and indigenous data sovereignty. This study was not designed as a discovery epigenome wide analysis, but rather performed, as an exemplar, a SWOT analysis that identified both the potential of DNAm markers, such as cg05575921 in AHRR for smoking exposure assessment, and key risks, including genetic confounding, population-specific variation, and the potential for individual and transgenerational stigma. Findings underscore the importance of ensuring multi-ethnic validation of DNAm markers to prevent exacerbation of health inequities. This paper advocates for the adoption of ethical, culturally attuned research frameworks in epigenetics to enhance equitable health outcomes and support Māori health advancement.