Indonesian populations exhibit a striking level of genetic diversity, including regional patterns of admixture, and varying degrees of introgression from Denisovans. Although recent studies have characterized patterns of genetic variation and admixture across the Indonesian archipelago, functional genomic data from the region lags far behind. Here, we provide a benchmark dataset of molecular phenotypes in Indonesia from over 100 individuals, integrating whole genome sequences, CpG methylation and RNA-sequencing data from three island populations that capture the major genomic and geographical axes of diversity across the region: Mentawai, representative of the dominant Asian ancestry; Korowai, from the island of New Guinea, and capturing the regional Papuan ancestry, and individuals from the island of Sumba, a near equal mixture of these two ancestries. With these data, we investigate between- and within-island patterns of variation, and find that both DNA methylation and gene expression are influenced by environmental and genetic factors, and that observed variation in gene expression is partially association with differences in DNA methylation, with the expression levels of 12.6% of the investigated genes strongly correlating with nearby CpG methylation. Our results strongly suggest a causal relationship between genetic variation, DNA methylation, transcription, and immunity, shaped by the environment. These findings have implications to genomic medicine in underrepresented Indonesia, and help us better understand the roles of genomic and environmental effects in shaping molecular and complex phenotypes.
In addition, to directly examine the genetic architecture of gene expression in Indonesia, we have begun to identify expression quantitative trait loci (eQTLs) in our sample. We present preliminary results from this work, including a comparison with eQTLs identified in European populations, to further refine our understanding of gene regulatory architecture across human populations.