Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy : An Integrative Epigenome Wide Association Study

Although there are some epigenome-wide association studies (EWAS) of insulin resistance, most of them did not replicate their findings and are focused in populations of European ancestry limiting the generalizability. In EPIPREG (294 Europeans and 162 South Asians), we conducted an EWAS of insulin resistance in maternal peripheral blood leukocytes, with replication in Born in Bradford (n=879; 430 Europeans and 449 South Asians), MENA (n=320) and Botnia (n=56) cohorts. In EPIPREG, we identified six CpG sites inversely associated with insulin resistance across ancestry, whereof five were replicated in independent cohorts (cg02988288, cg19693031, and cg26974062 in TXNIP, cg06690548 in SLC7A11, cg04861640 in ZSCAN26). From methylation quantitative trait loci analysis in EPIPREG, we identified gene variants related to all five replicated cross-ancestry CpG sites, which were associated with several cardiometabolic phenotypes. Mediation analyses suggested that the gene variants regulate insulin resistance through DNA methylation. To conclude, our cross-ancestry EWAS identified five CpG sites related with lower insulin resistance.

Elliott, H RUniversity of Bristol (författare)
Lee-Ødegård, SUniversity of Oslo (författare)
Opsahl, J OUniversity of Oslo (författare)
Sletner, LAkershus University Hospital (författare)
Jenum, A KUniversity of Oslo (författare)
Drevon, Christian AUniversity of Oslo (författare)
Qvigstad, EOslo university hospital (författare)
Moen, G-HOslo university hospital (författare)
Birkeland, K IOslo university hospital (författare)
Prasad, R BLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki(Swepub:lu)med-rpa (författare)
Sommer, COslo university hospital (författare)
Oslo university hospitalUniversity of Bristol (creator_code:org_t)

Ingår i:Diabetes: American Diabetes Association72:3, s. 415-4261939-327X0012-1797

Av författaren/redakt...: Fragoso-Bargas, ...; Elliott, H R; Lee-Ødegård, S; Opsahl, J O; Sletner, L; Jenum, A K; visa fler...; Drevon, Christia ...; Qvigstad, E; Moen, G-H; Birkeland, K I; Prasad, R B; Sommer, C; visa färre...

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