Preprint maps genetic and exposure-linked DNA methylation patterns in Black American brain tissue

Human brain DNA methylation is shaped by both inherited genetic variants and cumulative environmental experience, but how these two influences partition across the methylome has remained poorly characterised, particularly in ancestrally diverse cohorts. A preprint posted to bioRxiv in June 2026 reports findings from 168 admixed Black American adults drawn from the BrainSEQ consortium, for whom whole-genome bisulfite sequencing and genotype array data were available across three brain regions.

The authors adapted and benchmarked a SNP-based elastic-net modelling approach to classify variably methylated regions (VMRs) according to whether their variation is primarily explained by local genetic variants (genetically anchored) or by non-genetic, exposure-associated factors. The framework distinguishes between methylation quantitative trait loci (mQTL) effects and those reflecting environmental history, and the authors report that the resulting methylation architecture differs in important ways from findings in predominantly European-ancestry reference datasets.

The study addresses a recognised gap in epigenomic reference resources: most postmortem brain methylation studies have relied on cohorts of limited ancestral diversity, which constrains the generalisability of conclusions about gene–environment interactions in the brain. The findings are of primary interest to statistical geneticists, neuroepigenomics researchers, and those working on population diversity in genomic reference datasets. As a preprint, the work has not yet undergone peer review.