Fig 1.
Illustration of FADS gene cluster and sequenced region of interest.
(A) Illustration of FADS gene cluster on chromosome 11 with seven key SNPs in the FADS cluster marked. (B) Illustration of region between FADS1 and FADS2 that was bisulfite sequenced (61,584,720–61,595,166) with three key regulatory regions highlighted, namely: FADS1 promoter region (green), putative Enhancer region (yellow) and FADS2 promoter region (blue).
Table 1.
Population demographics and characteristics.
Fig 2.
Illustration of DNA methylation landscape across the sequenced region for European and African Americans.
Average DNA methylation levels for European Americans are denoted by blue circles and average DNA methylation for African Americans are shown as red circles. Highlighted regions correspond to the FADS1 promoter (green), putative enhancer (yellow) and FADS2 promoter (blue) regions. Dashed line represents 80% methylation. Triangle shaped points in the putative enhancer region are CpG sites that displayed significant ASM with rs174537 in the meta-analysis.
Fig 3.
Manhattan plot for association of rs174537 with CpG sites from the sequenced region between FADS1 and FADS2, showing the meta-analysis, and stratified by racial group.
European Americans are denoted by EA and African Americans are denoted by AA. CpG sites highlighted in orange displayed significant ASM associations (FDR P-value <0.05), based on the genetic trend test that was adjusted for age. The blue line represents the recombination rate.
Table 2.
Strongest associations between SNP rs174537 (coded for dominant genetic model, relative to T-allele) and CpG sites within the FADS1 and FADS2 sequenced region.
(A) Meta-analysis including both races, (B) Stratified analysis for European Americans only, and (C) Stratified analysis for African Americans only.
Fig 4.
Mean proportion of DNA methylation across the sequenced region is dependent on genotype at rs174537.
(A) Racial differences observed in the enhancer region (African American–red; European American–blue). (B) Genotype at rs174537 affects methylation status in the enhancer region (GG–red; GT/TT–blue). (C) No statistically significant differences between African American and European American both with GG genotype. (D) No statistically significant differences between African American and European American both with GT/TT genotype.